Hepatitis B virus seroepidemiology data for Africa: Modelling intervention strategies based on a systematic review and meta-analysis

Autoři: Anna L. McNaughton aff001;  José Lourenco aff002;  Phillip Armand Bester aff003;  Jolynne Mokaya aff001;  Sheila F. Lumley aff001;  Uri Obolski aff005;  Donall Forde aff007;  Tongai G. Maponga aff008;  Kenneth R. Katumba aff009;  Dominique Goedhals aff003;  Sunetra Gupta aff002;  Janet Seeley aff009;  Robert Newton aff009;  Ponsiano Ocama aff012;  Philippa C. Matthews aff001
Působiště autorů: Nuffield Department of Medicine, University of Oxford, Medawar Building for Pathogen Research, Oxford, United Kingdom aff001;  Department of Zoology, University of Oxford, Medawar Building for Pathogen Research, Oxford, United Kingdom aff002;  Division of Virology, University of the Free State and National Health Laboratory Service, Bloemfontein, South Africa aff003;  Department of Infectious Diseases and Microbiology, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Headington, Oxford, United Kingdom aff004;  School of Public Health, Tel Aviv University, Tel Aviv, Israel aff005;  Porter School of the Environment and Earth Sciences, Tel Aviv University, Tel Aviv, Israel aff006;  Nuffield Department of Medicine, Nuffield Department of Medicine Research Building, Headington, Oxford, United Kingdom aff007;  Division of Medical Virology, University of Stellenbosch, Faculty of Medicine and Health Sciences, Cape Town, South Africa aff008;  Medical Research Council/Uganda Virus Research Institute and London School of Hygiene and Tropical Medicine Uganda Research Unit, Entebbe, Uganda aff009;  Faculty of Global Health and Development, London School of Hygiene and Tropical Medicine, London, United Kingdom aff010;  Department of Health Sciences, University of York, York, United Kingdom aff011;  Makerere University College of Health Sciences, Kampala, Uganda aff012
Vyšlo v časopise: Hepatitis B virus seroepidemiology data for Africa: Modelling intervention strategies based on a systematic review and meta-analysis. PLoS Med 17(4): e1003068. doi:10.1371/journal.pmed.1003068
Kategorie: Research Article
doi: 10.1371/journal.pmed.1003068



International Sustainable Development Goals (SDGs) for elimination of hepatitis B virus (HBV) infection set ambitious targets for 2030. In African populations, infant immunisation has been fundamental to reducing incident infections in children, but overall population prevalence of chronic hepatitis B (CHB) infection remains high. In high-prevalence populations, adult catch-up vaccination has sometimes been deployed, but an alternative Test and Treat (T&T) approach could be used as an intervention to interrupt transmission. Universal T&T has not been previously evaluated as a population intervention for HBV infection, despite high-profile data supporting its success with human immunodeficiency virus (HIV).

Methods and findings

We set out to investigate the relationship between prevalence of HBV infection and exposure in Africa, undertaking a systematic literature review in November 2019. We identified published seroepidemiology data representing the period 1995–2019 from PubMed and Web of Science, including studies of adults that reported prevalence of both hepatitis B surface antigen (HBsAg; prevalence of HBV infection) and antibody to hepatitis B core antigen (anti-HBc; prevalence of HBV exposure). We identified 96 studies representing 39 African countries, with a median cohort size of 370 participants and a median participant age of 34 years. Using weighted linear regression analysis, we found a strong relationship between the prevalence of infection (HBsAg) and exposure (anti-HBc) (R2 = 0.45, p < 0.001). Region-specific differences were present, with estimated CHB prevalence in Northern Africa typically 30% to 40% lower (p = 0.007) than in Southern Africa for statistically similar exposure rates, demonstrating the need for intervention strategies to be tailored to individual settings. We applied a previously published mathematical model to investigate the effect of interventions in a high-prevalence setting. The most marked and sustained impact was projected with a T&T strategy, with a predicted reduction of 33% prevalence by 20 years (95% CI 30%–37%) and 62% at 50 years (95% CI 57%–68%), followed by routine neonatal vaccination and prevention of mother to child transmission (PMTCT; at 100% coverage). In contrast, the impact of catch-up vaccination in adults had a negligible and transient effect on population prevalence. The study is constrained by gaps in the published data, such that we could not model the impact of antiviral therapy based on stratification by specific clinical criteria and our model framework does not include explicit age-specific or risk-group assumptions regarding force of transmission.


The unique data set collected in this study highlights how regional epidemiology data for HBV can provide insights into patterns of transmission, and it provides an evidence base for future quantitative research into the most effective local interventions. In combination with robust neonatal immunisation programmes, ongoing PMTCT efforts, and the vaccination of high-risk groups, diagnosing and treating HBV infection is likely to be of most impact in driving advances towards elimination targets at a population level.

Klíčová slova:

Adults – Africa – Antibodies – Hepatitis B – Hepatitis B virus – HIV – Uganda – Vaccination and immunization


1. Polaris Observatory Collaborators. Global prevalence, treatment, and prevention of hepatitis B virus infection in 2016: a modelling study. Lancet Gastroenterol Hepatol. 2018;3(6):383–403. doi: 10.1016/S2468-1253(18)30056-6 29599078.

2. O'Hara GA, McNaughton AL, Maponga T, Jooste P, Ocama P, Chilengi R, et al. Hepatitis B virus infection as a neglected tropical disease. PLoS Negl Trop Dis. 2017;11(10):e0005842. doi: 10.1371/journal.pntd.0005842 28981505.

3. Bwogi J, Braka F, Makumbi I, Mishra V, Bakamutumaho B, Nanyunja M, et al. Hepatitis B infection is highly endemic in Uganda: findings from a national serosurvey. Afr Health Sci. 2009;9(2):98–108. 19652743.

4. Schweitzer A, Horn J, Mikolajczyk RT, Krause G, Ott JJ. Estimations of worldwide prevalence of chronic hepatitis B virus infection: a systematic review of data published between 1965 and 2013. Lancet. 2015;386(10003):1546–55. doi: 10.1016/S0140-6736(15)61412-X 26231459.

5. Dumpis U, Holmes EC, Mendy M, Hill A, Thursz M, Hall A, et al. Transmission of hepatitis B virus infection in Gambian families revealed by phylogenetic analysis. J Hepatol. 2001;35(1):99–104. doi: 10.1016/s0168-8278(01)00064-2 11495049.

6. Kiire CF. The epidemiology and prophylaxis of hepatitis B in sub-Saharan Africa: a view from tropical and subtropical Africa. Gut. 1996;38 Suppl 2:S5–12. doi: 10.1136/gut.38.suppl_2.s5 8786055.

7. Griggs D, Stafford-Smith M, Gaffney O, Rockstrom J, Ohman MC, Shyamsundar P, et al. Policy: Sustainable development goals for people and planet. Nature. 2013;495(7441):305–7. doi: 10.1038/495305a 23518546.

8. WHO. Guidelines for the Prevention, Care and Treatment of Persons with Chronic Hepatitis B Infection. https://www.who.int/hiv/pub/hepatitis/hepatitis-b-guidelines/en/ (2015) [cited 2019 July 1].

9. McNaughton A, Lourenco J, Hattingh L, Adland E, Daniels S, van Zyl A, et al. HBV vaccination and PMTCT as elimination tools in the presence of HIV: insights from a clinical cohort and dynamic model. BMC Med. 2019;17:43. doi: 10.1186/s12916-019-1269-x 30786896

10. Nayagam S, Thursz M, Sicuri E, Conteh L, Wiktor S, Low-Beer D, et al. Requirements for global elimination of hepatitis B: a modelling study. Lancet Infect Dis. 2016;16(12):1399–408. doi: 10.1016/S1473-3099(16)30204-3 27638356.

11. EASL. Clinical Practice Guidelines on the management of hepatitis B virus infection. J Hepatol. 2017;67(2):370–98. doi: 10.1016/j.jhep.2017.03.021 28427875.

12. Spearman CWN, Sonderup MW, Botha JF, van der Merwe SW, Song E, C K. South African guideline for the management of chronic hepatitis B. S Afr Med J. 2013;103:337–49. 23967497

13. NICE Clinical Guideline, Hepatitis B (chronic): diagnosis and management; Clinical guideline [CG165] (Published June 2013; Updated October 2017) 2013. nice.org.uk/guidance/cg165. [cited 2019 July 1].

14. McNaughton AL, D'Arienzo V, Ansari MA, Lumley SF, Littlejohn M, Revill P, et al. Insights From Deep Sequencing of the HBV Genome-Unique, Tiny, and Misunderstood. Gastroenterology. 2019;156(2):384–99. doi: 10.1053/j.gastro.2018.07.058 30268787.

15. Wilson P, Parr JB, Jhaveri R, Meshnick SR. Call to Action: Prevention of Mother-to-Child Transmission of Hepatitis B in Africa. J Infect Dis. 2018;217(8):1180–3. doi: 10.1093/infdis/jiy028 29351639.

16. Alavian SM. Decreasing the hepatitis B burden in Tunisia need more attention to adults for vaccination. Epidemiology and infection. 2017;145(7):1512. doi: 10.1017/S0950268817000061 28202090.

17. Ampurire P. Hepatitis B Vaccination: Health Ministry Reports Significant Drop in Coverage of Follow-Up Doses (https://www.softpower.ug/hepatitis-b-vaccination-health-ministry-reports-significant-drop-in-coverage-of-follow-up-doses/). Soft Power News. 2019. [cited 2019 July 1].

18. Wright CM, Boudarene L, Ha NT, Wu O, Hawkins N. A systematic review of hepatitis B screening economic evaluations in low- and middle-income countries. BMC Public Health. 2018;18(1):373. doi: 10.1186/s12889-018-5261-8 29558894.

19. Lemoine M, Shimakawa Y, Njie R, Taal M, Ndow G, Chemin I, et al. Acceptability and feasibility of a screen-and-treat programme for hepatitis B virus infection in The Gambia: the Prevention of Liver Fibrosis and Cancer in Africa (PROLIFICA) study. Lancet Glob Health. 2016;4(8):e559–67. doi: 10.1016/S2214-109X(16)30130-9 27443781.

20. Weber J, Tatoud R, Fidler S. Postexposure prophylaxis, preexposure prophylaxis or universal test and treat: the strategic use of antiretroviral drugs to prevent HIV acquisition and transmission. AIDS. 2010;24 Suppl 4:S27–39. doi: 10.1097/01.aids.0000390705.73759.2c 21042050.

21. Cohen MS, Chen YQ, McCauley M, Gamble T, Hosseinipour MC, Kumarasamy N, et al. Antiretroviral Therapy for the Prevention of HIV-1 Transmission. New England Journal of Medicine. 2016;375(9):830–9. doi: 10.1056/NEJMoa1600693 27424812.

22. Ford N, Migone C, Calmy A, Kerschberger B, Kanters S, Nsanzimana S, et al. Benefits and risks of rapid initiation of antiretroviral therapy. AIDS. 2018;32(1):17–23. doi: 10.1097/QAD.0000000000001671 29112073

23. Ndow G, Gore ML, Shimakawa Y, Suso P, Jatta A, Tamba S, et al. Hepatitis B testing and treatment in HIV patients in The Gambia-Compliance with international guidelines and clinical outcomes. PLoS One. 2017;12(6):e0179025. doi: 10.1371/journal.pone.0179025 28614401.

24. United Nations Geoscheme for Africa. https://unstats.un.org/home/about/. [cited 2019 July 1].

25. The Joanna Briggs Institute Critical Appraisal tools for use in JBI Systematic Reviews: Checklist for Prevalence Studies. http://joannabriggs-webdev.org/research/critical-appraisal-tools.html. [cited 201 July 1].

26. Munn Z, Moola S, Lisy K, Riitano D, Tufanaru C. Methodological guidance for systematic reviews of observational epidemiological studies reporting prevalence and cumulative incidence data. Int J Evid Based Healthc. 2015;13(3):147–53. doi: 10.1097/XEB.0000000000000054 26317388.

27. R Core Team. R: A language and environment for statistical computing. 2013.

28. Bester PA. https://github.com/ArmandBester/Serology_of_HBV_in_Africa. 2018. [cited 2019 July 1].

29. Bester PA. Visualisation of HBV sero-epidemiology data for Africa. https://hbv-geo.shinyapps.io/oxafricahbv/. 2018. [cited 2019 July 1].

30. Mphahlele MJ, Lukhwareni A, Burnett RJ, Moropeng LM, Ngobeni JM. High risk of occult hepatitis B virus infection in HIV-positive patients from South Africa. J Clin Virol. 2006;35(1):14–20. Epub 2005/05/27. doi: 10.1016/j.jcv.2005.04.003 15916918.

31. Nakwagala FN, Kagimu MM. Hepatitis B virus and hiv infections among patients in Mulago hospital. East Afr Med J. 2002;79(2):68–72. doi: 10.4314/eamj.v79i2.8903 12380879.

32. Mayaphi SH, Roussow TM, Masemola DP, Olorunju SA, Mphahlele MJ, Martin DJ. HBV/HIV co-infection: the dynamics of HBV in South African patients with AIDS. S Afr Med J. 2012;102(3 Pt 1):157–62. doi: 10.7196/samj.4944 22380911.

33. Adoga MP, Gyar SD, Pechulano S, Bashayi OD, Emiasegen SE, Zungwe T, et al. Hepatitis B virus infections in apparently healthy urban Nigerians: data from pre-vaccination tests. Journal of infection in developing countries. 2010;4(6):397–400. 20601793.

34. Burnett RJ, Kramvis A, Dochez C, Meheus A. An update after 16 years of hepatitis B vaccination in South Africa. Vaccine. 2012;30 Suppl 3:C45–51. Epub 2012/09/04. doi: 10.1016/j.vaccine.2012.02.021 22939021.

35. Abebe A, Nokes DJ, Dejene A, Enquselassie F, Messele T, Cutts FT. Seroepidemiology of hepatitis B virus in Addis Ababa, Ethiopia: transmission patterns and vaccine control. Epidemiology and infection. 2003;131(1):757–70. doi: 10.1017/s0950268803008574 12948377.

36. Mokaya J, McNaughton A, Burbridge L, Maponga T, O'Hara GA, Andersson M, et al. A blind spot? Confronting the stigma of hepatitis B virus (HBV) infection—A systematic review [version 2; referees: 2 approved]. Wellcome Open Res 2018;3:29. doi: 10.12688/wellcomeopenres.14273.2 30483598

37. Mugisha J, Mokaya J, Bukenya D, Ssembajja F, Mayambala D, Newton R, et al. A Study of Knowledge, Experience, and Beliefs About Hepatitis B Virus (HBV) Infection in South Western Uganda. Front Public Health. 2019;7:304. doi: 10.3389/fpubh.2019.00304 31709217.

38. Pearson A, Jordan Z. Evidence-based healthcare in developing countries. Int J Evid Based Healthc. 2010;8(2):97–100. 21077397.

39. Mahgoub S, Candotti D, El Ekiaby M, Allain JP. Hepatitis B virus (HBV) infection and recombination between HBV genotypes D and E in asymptomatic blood donors from Khartoum, Sudan. J Clin Microbiol. 2011;49(1):298–306. doi: 10.1128/JCM.00867-10 21048009.

40. Collenberg E, Ouedraogo T, Ganame J, Fickenscher H, Kynast-Wolf G, Becher H, et al. Seroprevalence of six different viruses among pregnant women and blood donors in rural and urban Burkina Faso: A comparative analysis. J Med Virol. 2006;78(5):683–92. doi: 10.1002/jmv.20593 16555290.

41. Jia Y, Li L, Cui F, Zhang D, Zhang G, Wang F, et al. Cost-effectiveness analysis of a hepatitis B vaccination catch-up program among children in Shandong Province, China. Hum Vaccin Immunother. 2014;10(10):2983–91. doi: 10.4161/hv.29944 25483678.

42. Butler EK, Rodgers MA, Coller KE, Barnaby D, Krilich E, Olivo A, et al. High prevalence of hepatitis delta virus in Cameroon. Sci Rep. 2018;8(1):11617. doi: 10.1038/s41598-018-30078-5 30072752.

43. Nayagam S, Conteh L, Sicuri E, Shimakawa Y, Suso P, Tamba S, et al. Cost-effectiveness of community-based screening and treatment for chronic hepatitis B in The Gambia: an economic modelling analysis. Lancet Glob Health. 2016;4(8):e568–78. doi: 10.1016/S2214-109X(16)30101-2 27443782.

44. Brown AE, Nardone A, Delpech VC. WHO 'Treatment as Prevention' guidelines are unlikely to decrease HIV transmission in the UK unless undiagnosed HIV infections are reduced. AIDS. 2014;28(2):281–3. doi: 10.1097/QAD.0000000000000137 24361685.

45. Mokaya J, McNaughton AL, Hadley MJ, Beloukas A, Geretti AM, Goedhals D, et al. A systematic review of hepatitis B virus (HBV) drug and vaccine escape mutations in Africa: A call for urgent action. PLoS Negl Trop Dis. 2018;12(8):e0006629. doi: 10.1371/journal.pntd.0006629 30080852.

46. Whittle H, Inskip H, Bradley AK, McLaughlan K, Shenton F, Lamb W, et al. The pattern of childhood hepatitis B infection in two Gambian villages. J Infect Dis. 1990;161(6):1112–5. doi: 10.1093/infdis/161.6.1112 2345294.

47. Rajoriya N, Combet C, Zoulim F, Janssen HLA. How viral genetic variants and genotypes influence disease and treatment outcome of chronic hepatitis B. Time for an individualised approach? J Hepatol. 2017;67(6):1281–97. doi: 10.1016/j.jhep.2017.07.011 28736138.

48. Olinger CM, Venard V, Njayou M, Oyefolu AO, Maiga I, Kemp AJ, et al. Phylogenetic analysis of the precore/core gene of hepatitis B virus genotypes E and A in West Africa: new subtypes, mixed infections and recombinations. The Journal of general virology. 2006;87(Pt 5):1163–73. doi: 10.1099/vir.0.81614-0 16603517.

49. Matthews PC, Geretti AM, Goulder PJ, Klenerman P. Epidemiology and impact of HIV coinfection with hepatitis B and hepatitis C viruses in Sub-Saharan Africa. J Clin Virol. 2014;61(1):20–33. doi: 10.1016/j.jcv.2014.05.018 24973812.

50. Eke CB, Ogbodo SO, Ukoha OM, Ibekwe RC, Asinobi IN, Ikefuna AN, et al. Seroprevalence and Risk Factors of Hepatitis B Virus Infection among Adolescents in Enugu, Nigeria. J Trop Pediatr. 2015;61(6):407–13. doi: 10.1093/tropej/fmv035 26411561.

51. Kramvis A, Kew M, Francois G. Hepatitis B virus genotypes. Vaccine. 2005;23(19):2409–23. doi: 10.1016/j.vaccine.2004.10.045 15752827.

52. Tan AT, Loggi E, Boni C, Chia A, Gehring AJ, Sastry KS, et al. Host ethnicity and virus genotype shape the hepatitis B virus-specific T-cell repertoire. J Virol. 2008;82(22):10986–97. doi: 10.1128/JVI.01124-08 18799575.

53. Matthews PC, Carlson JM, Beloukas A, Malik A, Jooste P, Ogwu A, et al. HLA-A is a Predictor of Hepatitis B e Antigen Status in HIV-Positive African Adults. J Infect Dis. 2016;213(8):1248–52. doi: 10.1093/infdis/jiv592 26655301.

54. Lumley S, Noble H, Hadley MJ, Callow L, Malik A, Chua YY, et al. Hepitopes: A live interactive database of HLA class I epitopes in hepatitis B virus. Wellcome Open Res. 2016;1:9. doi: 10.12688/wellcomeopenres.9952.1 27976751.

55. Lin CL, Kao JH. The clinical implications of hepatitis B virus genotype: Recent advances. Journal of gastroenterology and hepatology. 2011;26 Suppl 1:123–30. doi: 10.1111/j.1440-1746.2010.06541.x 21199523.

56. WHO. Hepatitis B Fact Sheet 2017; http://www.who.int/mediacentre/factsheets/fs204/en/. [cited 2019 July 1].

57. Bulteel N, Partha Sarathy P, Forrest E, Stanley AJ, Innes H, Mills PR, et al. Factors associated with spontaneous clearance of chronic hepatitis C virus infection. J Hepatol. 2016;65(2):266–72. doi: 10.1016/j.jhep.2016.04.030 27155531.

58. Sheen IS, Liaw YF, Chu CM, Pao CC. Role of hepatitis C virus infection in spontaneous hepatitis B surface antigen clearance during chronic hepatitis B virus infection. J Infect Dis. 1992;165(5):831–4. doi: 10.1093/infdis/165.5.831 1314869.

59. Cooke GS, Andrieux-Meyer I, Applegate TL, Atun R, Burry JR, Cheinquer H, et al. Accelerating the elimination of viral hepatitis: a Lancet Gastroenterology & Hepatology Commission. Lancet Gastroenterol Hepatol. 2019;4(2):135–84. doi: 10.1016/S2468-1253(18)30270-X 30647010.

60. Shimakawa Y, Njie R, Ndow G, Vray M, Mbaye PS, Bonnard P, et al. Development of a simple score based on HBeAg and ALT for selecting patients for HBV treatment in Africa. J Hepatol. 2018;69(4):776–84. doi: 10.1016/j.jhep.2018.05.024 30104154.

61. Aberra H, Desalegn H, Berhe N, Mekasha B, Medhin G, Gundersen SG, et al. The WHO guidelines for chronic hepatitis B fail to detect half of the patients in need of treatment in Ethiopia. J Hepatol. 2019;70(6):1065–71. doi: 10.1016/j.jhep.2019.01.037 30929749.

62. Coffin CS, Zhou K, Terrault NA. New and Old Biomarkers for Diagnosis and Management of Chronic Hepatitis B Virus Infection. Gastroenterology. 2019;156(2):355–68.e3. doi: 10.1053/j.gastro.2018.11.037 30472225.

63. Mokaya J, Burn E, Raissa Tamandjou C, Goedhals D, Barnes E, Andersson M, et al. Modelling cost-effectiveness of tenofovir for prevention of mother to child transmission of hepatitis B virus infection in South Africa. BMC Public Health. 2019;19(1):829. doi: 10.1186/s12889-019-7095-4 31242901

64. Matthews PC, Beloukas A, Malik A, Carlson JM, Jooste P, Ogwu A, et al. Prevalence and Characteristics of Hepatitis B Virus (HBV) Coinfection among HIV-Positive Women in South Africa and Botswana. PLoS One. 2015;10(7):e0134037. doi: 10.1371/journal.pone.0134037 26218239.

Interní lékařství

Článek vyšel v časopise

PLOS Medicine

2020 Číslo 4

Nejčtenější v tomto čísle

Tomuto tématu se dále věnují…

Kurzy Doporučená témata Časopisy
Zapomenuté heslo

Nemáte účet?  Registrujte se

Zapomenuté heslo

Zadejte e-mailovou adresu se kterou jste vytvářel(a) účet, budou Vám na ni zaslány informace k nastavení nového hesla.


Nemáte účet?  Registrujte se

VIRTUÁLNÍ ČEKÁRNA ČR Jste praktický lékař nebo pediatr? Zapojte se! Jste praktik nebo pediatr? Zapojte se!