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Open Access 01-12-2020 | Hepatitis B | Research article

Viral hepatitis B and C in HIV-exposed South African infants

Authors: Cynthia Tamandjou Tchuem, Mark Fredric Cotton, Etienne Nel, Richard Tedder, Wolfgang Preiser, Avy Violari, Raziya Bobat, Laura Hovind, Lisa Aaron, Grace Montepiedra, Charles Mitchell, Monique Ingrid Andersson

Published in: BMC Pediatrics | Issue 1/2020

Abstract

Background

Whilst much attention is given to eliminating HIV mother-to-child transmission (MTCT), little has been done to ensure the same for hepatitis B virus (HBV) transmission. The introduction of HBV immunization at six weeks of age has reduced HBV horizontal transmission in South Africa. However, in order to eliminate HBV MTCT, further interventions are needed. The risk of hepatitis C virus (HCV) MTCT in HIV-infected (HIV+) African women is not yet well described. This study aimed to determine the rate of HBV and HCV vertical transmission in HIV-exposed infants in South Africa.

Methods

Serum samples from infants enrolled in an isoniazid prevention study (P1041) were screened for HBV and HCV serology markers; screening was performed on samples collected at approximately 60 weeks of age of the infants. HBV DNA was quantified in HBsAg positive samples and HBV strains characterized through gene sequencing. All HCV antibody samples with inconclusive results underwent molecular testing.

Results

Three of 821 infants were positive for both HBsAg and HBV DNA. All HBV strains belonged to HBV sub-genotype A1. The rtM204I mutation associated with lamivudine resistance was identified in one infant, a second infant harboured the double A1762T/G1764A BCP mutation. Phylogenetic analysis showed clustering between mother and infant viral genomic sequences. Twenty-one of 821 HIV-exposed infants tested had inconclusive HCV antibody results, none were HCV PCR positive.

Conclusions

This study suggests that HBV vertical transmission is likely to be occurring in HIV-exposed infants in South Africa.. A more robust strategy of HBV prevention, including birth dose vaccination, is required to eradicate HBV MTCT. HCV infection was not detected.

Lozano R, Naghavi M, Foreman K, Lim S, Shibuya K, Aboyans V, et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2013;380:2095–128. https://doi.org/10.1016/S0140-6736(12)61728-0.CrossRef

World Health Organization. Hepatitis B. 2019. http://www.who.int/mediacentre/factsheets/fs204/en/. (Accessed 09 Feb 2018).

World Health Organization. Hepatitis C. 2019. http://www.who.int/mediacentre/factsheets/fs164/en/. (Accessed 09 Feb 2018).

Prozesky OW, Szmuness W, Stevens CE, Kew MC, Harley EJ, Hoyland JA, et al. Baseline epidemiological studies for a hepatitis B vaccine trial in Kangwane. S Afr Med J. 1983;64:891–3.PubMed

Botha JF, Dusheiko GM, Ritchie MJJ, Mouton HW, Kew MC. Hepatitis B virus carrier state in black children in Ovamboland: role of perinatal and horizontal infection. Lancet. 1984;323:1210–2. https://doi.org/10.1016/S0140-6736(84)91694-5.CrossRef

Amponsah-Dacosta E, Lebelo RL, Rakgole JN, Burnett RJ, Selabe SG, Mphahlele MJ. Evidence for a change in the epidemiology of hepatitis B virus infection after nearly two decades of universal hepatitis B vaccination in South Africa. J Med Virol. 2014;86:918–24. https://doi.org/10.1002/jmv.23910.CrossRefPubMed

Keane E, Funk AL, Shimakawa Y. Systematic review with meta-analysis: the risk of mother-to-child transmission of hepatitis B virus infection in sub-Saharan Africa. Aliment Pharmacol Ther. 2016;44:1005–17. https://doi.org/10.1111/apt.13795.CrossRefPubMed

World Health Organization. Hepatitis B vaccines: WHO position paper – July 2017. Wkly Epidemiol Rec. 2017;27:369–92.

Woodring J, Pastore R, Brink A, Ishikawa N, Takashima Y, Tohme RA. Progress Toward Hepatitis B Control and Elimination of Mother-to-Child Transmission of Hepatitis B Virus - Western Pacific Region, 2005–2017. Morb Mortal Wkly Rep. 2019;68:195–200. 10.15585/mmwr.mm6808a2.CrossRef

10.

World Health Organization. Global hepatitis report, 2017. 2018 https://apps.who.int/iris/bitstream/handle/10665/255016/9789241565455-eng.pdf?sequence=1. (Accessed 22 Mar 2018).

11.

Andersson MI, Maponga TG, Ijaz S, Theron G, Preiser W, Tedder RS. High HBV viral loads in HIV-infected pregnant women at a tertiary hospital, South Africa. J Acquir Immune Defic Syndr. 2012;60:e111-2. https://doi.org/10.1097/QAI.0b013e31825aeee7.CrossRefPubMed

12.

Chasela CS, Kourtis AP, Wall P, Drobeniuc J, King CC, Thai H, et al. Hepatitis B virus infection among HIV-infected pregnant women in Malawi and transmission to infants. J Hepatol. 2014;60:508–14. https://doi.org/10.1016/j.jhep.2013.10.029.CrossRefPubMed

13.

Andersson M, Maponga T, Ijaz S, Barnes J, Theron GB, Meredith SA, et al. The epidemiology of hepatitis B virus infection in HIV-infected and HIV-uninfected pregnant women in the Western Cape, South Africa. Vaccine. 2013;31:5579–84. https://doi.org/10.1016/j.vaccine.2013.08.028.CrossRefPubMedPubMedCentral

14.

Thumbiran NV, Moodley D, Parboosing R, Moodley P. Hepatitis B and HIV co-infection in pregnant women: Indication for routine antenatal hepatitis B virus screening in a high HIV prevalence setting. S Afr Med J. 2014;104:307–9. https://doi.org/10.7196/SAMJ.7299.CrossRefPubMed

15.

Burnett RJ, Ngobeni JM, François G, Hoosen AA, Leroux-Roels G, Meheus A, et al. Increased exposure to hepatitis B virus infection in HIV-positive South African antenatal women. Int J STD AIDS. 2007;18:152–6. https://doi.org/10.1258/095646207780132523.CrossRefPubMed

16.

Umar M, Hamama-Tul-Bushra, Umar S, Khan HA. HBV Perinatal Transmission. . Int J Hepatol. 2013;2013:875791–7. https://doi.org/10.1155/2013/875791.CrossRefPubMedPubMedCentral

17.

Mora N, Adams WH, Kliethermes S, Dugas L, Balasubramanian N, Sandhu J, et al. A synthesis of hepatitis C prevalence estimates in sub-Saharan Africa: 2000–2013. BMC Infect Dis. 2016;16:283. https://doi.org/10.1186/s12879-016-1584-1.CrossRefPubMedPubMedCentral

18.

Karoney MJ, Siika AM. Hepatitis C virus (HCV) infection in Africa: a review. Pan Afr Med J. 2013;14:44. https://doi.org/10.11604/pamj.2013.14.44.2199.CrossRefPubMedPubMedCentral

19.

Madhi SA, Nachman S, Violari A, Kim S, Cotton MF, Bobat R, et al. Primary isoniazid prophylaxis against tuberculosis in HIV-exposed children. N Engl J Med. 2011;365:21–31. https://doi.org/10.1056/NEJMoa1011214.CrossRefPubMedPubMedCentral

20.

Garson JA, Grant PR, Ayliffe U, Ferns RB, Tedder RS. Real-Time PCR. Quantitation of Hepatitis B Virus DNA using Automated Sample Preparation and Murine Cytomegalovirus Internal Control. J Virol Methods. 2005;126:207–13. https://doi.org/10.1016/j.jviromet.2005.03.001.CrossRefPubMed

21.

Dervisevic S, Ijaz S, Chaudry S, Tedder RS. Non-A hepatitis B virus genotypes in antenatal clinics, United Kingdom. Emerg Infect Diseases. 2007;13:1689–93. https://doi.org/10.3201/eid1311.070578.CrossRef

22.

Public Health England. Recommended Protocol for HBV genotyping and for antiviral resistance analysis. 2007. https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/342414/cfi_vrd_PolHBsAgRecommendationsFINAL_HBV_protocol.pdf. (Accessed 09 Feb 2018).

23.

Tamura K, Stecher G, Peterson D, Filipski A, Kumar S. MEGA6: Molecular Evolutionary Genetics Analysis version 6.0. Mol Biol Evol. 2013;30:2725–9. https://doi.org/10.1093/molbev/mst197.CrossRefPubMedPubMedCentral

24.

Tavaré S. Some probabilistic and statistical problems in the analysis of DNA sequences. In: Miura RM, editor. Some Mathematical Questions in Biology - DNA Sequence Analysis. Providence: Amer Math Soc; 1986. p. 57–86.

25.

Yang Z. Maximum likelihood phylogenetic estimation from DNA sequences with variable rates over sites: approximate methods. J Mol Evol. 1994;39:306–14. https://doi.org/10.1007/BF00160154.CrossRefPubMed

26.

Vos GH, Rose EF, Marimuthu T. Hepatitis B, Antigen. and Antibodies in Rural and Urban Southern African Blacks. S Afr Med J. 1980;57:868–70.PubMed

27.

Abdool Karim SS, Coovadia HM, Windsor IM, Thejpal R, Van Den Ende JA, Fouche A. The Prevalence and Transmission of Hepatitis B Virus Infection in Urban, Rural and Institutionalized Black Children of Natal/KwaZulu, South Africa. Int J Epidemiol. 1988;17:168–73. https://doi.org/10.1093/ije/17.1.168.CrossRefPubMed

28.

Kew M, Miller G, Stevenson C, Macnab GM, Bersohn I. The Prevalence of Virus-B Hepatitis South African Blacks. S Afr Med J. 1974;48:1837–8.PubMed

29.

Tsebe KV, Burnett RJ, Hlungwani NP, Sibara MM, Venter PA, Mphahlele MJ. The first five years of universal hepatitis B vaccination in South Africa: evidence for elimination of HBsAg carriage in under 5-year-olds. Vaccine. 2001;19:3919–26. https://doi.org/10.1016/S0264-410X(01)00120-7.CrossRefPubMed

30.

Hino K, Katoh Y, Vardas E, Sim J, Okita K, Carman WF. The effect of introduction of universal childhood hepatitis B immunization in South Africa on the prevalence of serologically negative hepatitis B virus infection and the selection of immune escape variants. Vaccine. 2001;19:3912–18. https://doi.org/10.1016/S0264-410X(01)00121-9.CrossRefPubMed

31.

Mphahlele M, Francois G, Kew M, Van Damme P, Hoosen AA, Meheus A. Epidemiology and Control of Hepatitis B: Implications for Eastern and Southern Africa. South Afr J Epidemiol Infect. 2002;17:12–7.

32.

Schoub BD, Matai U, Singh B, Blackburn NK, Levin JB. Universal immunization of infants with low doses of a low-cost, plasma-derived hepatitis B vaccine in South Africa. Bull World Health Organ. 2002;80:277–81.PubMedPubMedCentral

33.

Simani OE, Leroux-Roels G, François G, Burnett RJ, Meheus A, Mphahlele MJ. Reduced detection and levels of protective antibodies to hepatitis B vaccine in under 2-year-old HIV positive South African children at a paediatric outpatient clinic. Vaccine. 2009;27:146–51. https://doi.org/10.1016/j.vaccine.2008.10.004.CrossRefPubMed

34.

Thio CL. Hepatitis B and human immunodeficiency virus coinfection. Hepatology. 2009;49:138-45. https://doi.org/10.1002/hep.22883.CrossRef

35.

Paganelli M, Stephenne X, Sokal EM. Chronic hepatitis B in children and adolescents. J Hepatol. 2012;57:885–96. https://doi.org/10.1016/j.jhep.2012.03.036.CrossRefPubMed

36.

Hoffmann CJ, Mashabela F, Cohn S, Hoffmann JD, Lala S, Martinson NA, et al. Maternal hepatitis B and infant infection among pregnant women living with HIV in South Africa. J Int AIDS Soc. 2014;17:18871. https://doi.org/10.7448/IAS.17.1.18871.CrossRefPubMedPubMedCentral

37.

Chotun N, Nel E, Cotton MF, Andersson MI. Hepatitis B virus infection in HIV-exposed infants in the Western Cape, South Africa. Vaccine. 2015;33:4618–22. https://doi.org/10.1016/j.vaccine.2015.06.076.CrossRefPubMed

38.

Lee C, Gong Y, Brok J, Boxall EH, Gluud C. Hepatitis B immunisation for newborn infants of hepatitis B surface antigen-positive mothers. Evid Based Child Health. 2006;2:67–155.CrossRef

39.

Poovorawan Y, Chongsrisawat V, Theamboonlers A, Srinivasa K, Hutagalung Y, Bock HL, et al. Long-term benefit of hepatitis B vaccination among children in Thailand with transient hepatitis B virus infection who were born to hepatitis B surface antigen-positive mothers. J Infect Dis. 2009;200:33–8. https://doi.org/10.1086/599331.CrossRefPubMed

40.

Evans AA, Cohen C, Huang P, Qian L, London WT, Block JM, et al. Prevention of perinatal hepatitis B transmission in Haimen City, China: Results of a community public health initiative. Vaccine. 2015;33:3010–15. https://doi.org/10.1016/j.vaccine.2015.01.054.CrossRefPubMed

41.

Sellier P, Maylin S, Amarsy R, Mazeron MC, Larrouy L, Haïm-Boukobza S, et al. Untreated highly viraemic pregnant women from Asia or sub‐Saharan Africa often transmit hepatitis B virus despite serovaccination to newborns. Liver Int. 2015;35:409–16. https://doi.org/10.1111/liv.12561.CrossRefPubMed

42.

Chakvetadze C, Roussin C, Roux J, Mallet V, Petinelli ME, Pol S. Efficacy of hepatitis B sero-vaccination in newborns of African HBsAg positive mothers. Vaccine. 2011;29:2846–9. https://doi.org/10.1016/j.vaccine.2011.01.101.CrossRefPubMed

43.

Yahyapour Y, Karimi M, Molaei HR, Khoddami E, Mahmoudi M. Active-passive Immunization Effectiveness Against Hepatitis B Virus in Children Born to HBsAg Positive Mothers in Amol, North of Iran. Oman Med J. 2011;26:399–403. https://doi.org/10.5001/omj.2011.103.CrossRefPubMedPubMedCentral

44.

Köse S, Türken M, Devrim İ, Taner C. Efficacy and safety of lamivudine treatment in late pregnancy with high HBV DNA: a perspective for mother and infants. J Infect Dev Ctries. 2011;5:303–6. https://doi.org/10.3855/jidc.1398.CrossRefPubMed

45.

Greenup AJ, Tan PK, Nguyen V, Glass A, Davison S, Chatterjee U, et al. Efficacy and safety of tenofovir disoproxil fumarate in pregnancy to prevent perinatal transmission of hepatitis B virus. J Hepatol. 2014;61:502–7. https://doi.org/10.1016/j.jhep.2014.04.038.CrossRefPubMed

46.

Han G, Jiang H, Yue X, Ding Y, Wang CM, Wang GJ, et al. Efficacy and safety of telbivudine treatment: an open-label, prospective study in pregnant women for the prevention of perinatal transmission of hepatitis B virus infection. J Viral Hepat. 2015;22:754–62. https://doi.org/10.1111/jvh.12379.CrossRefPubMed

Title: Viral hepatitis B and C in HIV-exposed South African infants
Authors: Cynthia Tamandjou Tchuem
Mark Fredric Cotton
Etienne Nel
Richard Tedder
Wolfgang Preiser
Avy Violari
Raziya Bobat
Laura Hovind
Lisa Aaron
Grace Montepiedra
Charles Mitchell
Monique Ingrid Andersson
Publication date: 01-12-2020
Publisher: BioMed Central
Keywords: Hepatitis B
Lamivudine
Human Immunodeficiency Virus
Hepatitis C
Lamivudine
Published in: BMC Pediatrics / Issue 1/2020
Electronic ISSN: 1471-2431
DOI: https://doi.org/10.1186/s12887-020-02479-x

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Viral hepatitis B and C in HIV-exposed South African infants

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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