PMID- 30786896 OWN - NLM STAT- MEDLINE DCOM- 20191113 LR - 20231130 IS - 1741-7015 (Electronic) IS - 1741-7015 (Linking) VI - 17 IP - 1 DP - 2019 Feb 21 TI - HBV vaccination and PMTCT as elimination tools in the presence of HIV: insights from a clinical cohort and dynamic model. PG - 43 LID - 10.1186/s12916-019-1269-x [doi] LID - 43 AB - BACKGROUND: Sustainable Development Goals set a challenge for the elimination of hepatitis B virus (HBV) infection as a public health concern by the year 2030. Deployment of a robust prophylactic vaccine and enhanced interventions for prevention of mother to child transmission (PMTCT) are cornerstones of elimination strategy. However, in light of the estimated global burden of 290 million cases, enhanced efforts are required to underpin optimisation of public health strategy. Robust analysis of population epidemiology is particularly crucial for populations in Africa made vulnerable by HIV co-infection, poverty, stigma and poor access to prevention, diagnosis and treatment. METHODS: We here set out to evaluate the current and future role of HBV vaccination and PMTCT as tools for elimination. We first investigated the current impact of paediatric vaccination in a cohort of children with and without HIV infection in Kimberley, South Africa. Second, we used these data to inform a new parsimonious model to simulate the ongoing impact of preventive interventions. By applying these two approaches in parallel, we are able to determine both the current impact of interventions, and the future projected outcome of ongoing preventive strategies over time. RESULTS: Existing efforts have been successful in reducing paediatric prevalence of HBV infection in this setting to < 1%, demonstrating the success of the existing vaccine campaign. Our model predicts that, if consistently deployed, combination efforts of vaccination and PMTCT can significantly reduce population prevalence (HBsAg) by 2030, such that a major public health impact is possible even without achieving elimination. However, the prevalence of HBV e-antigen (HBeAg)-positive carriers will decline more slowly, representing a persistent population reservoir. We show that HIV co-infection significantly reduces titres of vaccine-mediated antibody, but has a relatively minor role in influencing the projected time to elimination. Our model can also be applied to other settings in order to predict impact and time to elimination based on specific interventions. CONCLUSIONS: Through extensive deployment of preventive strategies for HBV, significant positive public health impact is possible, although time to HBV elimination as a public health concern is likely to be substantially longer than that proposed by current goals. FAU - McNaughton, Anna L AU - McNaughton AL AD - Nuffield Department of Medicine, Peter Medawar Building for Pathogen Research, South Parks Road, Oxford, OX1 3SY, UK. FAU - Lourenco, Jose AU - Lourenco J AD - Department of Zoology, Peter Medawar Building for Pathogen Research, South Parks Road, Oxford, OX1 3SY, UK. FAU - Hattingh, Louise AU - Hattingh L AD - Department of Paediatrics, Kimberley Hospital, Kimberley, 8300, South Africa. FAU - Adland, Emily AU - Adland E AD - Department of Paediatrics, Peter Medawar Building for Pathogen Research, South Parks Road, Oxford, OX1 3SY, UK. FAU - Daniels, Samantha AU - Daniels S AD - Department of Paediatrics, Kimberley Hospital, Kimberley, 8300, South Africa. FAU - Van Zyl, Anriette AU - Van Zyl A AD - Department of Paediatrics, Kimberley Hospital, Kimberley, 8300, South Africa. FAU - Akiror, Connie S AU - Akiror CS AD - Global Healthcare Public Foundation, Makindu Lane, Kololo, Kampala, Uganda. FAU - Wareing, Susan AU - Wareing S AD - Department of Infectious Diseases and Microbiology, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Headley Way, Oxford, OX3 9DU, UK. FAU - Jeffery, Katie AU - Jeffery K AD - Department of Infectious Diseases and Microbiology, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Headley Way, Oxford, OX3 9DU, UK. FAU - Ansari, M Azim AU - Ansari MA AD - Nuffield Department of Medicine, Peter Medawar Building for Pathogen Research, South Parks Road, Oxford, OX1 3SY, UK. FAU - Klenerman, Paul AU - Klenerman P AD - Nuffield Department of Medicine, Peter Medawar Building for Pathogen Research, South Parks Road, Oxford, OX1 3SY, UK. AD - Department of Infectious Diseases and Microbiology, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Headley Way, Oxford, OX3 9DU, UK. FAU - Goulder, Philip J R AU - Goulder PJR AD - Department of Paediatrics, Peter Medawar Building for Pathogen Research, South Parks Road, Oxford, OX1 3SY, UK. FAU - Gupta, Sunetra AU - Gupta S AD - Department of Zoology, Peter Medawar Building for Pathogen Research, South Parks Road, Oxford, OX1 3SY, UK. FAU - Jooste, Pieter AU - Jooste P AD - Department of Paediatrics, Kimberley Hospital, Kimberley, 8300, South Africa. FAU - Matthews, Philippa C AU - Matthews PC AUID- ORCID: 0000-0002-4036-4269 AD - Nuffield Department of Medicine, Peter Medawar Building for Pathogen Research, South Parks Road, Oxford, OX1 3SY, UK. philippa.matthews@ndm.ox.ac.uk. AD - Department of Infectious Diseases and Microbiology, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Headley Way, Oxford, OX3 9DU, UK. philippa.matthews@ndm.ox.ac.uk. LA - eng GR - 104748/WT_/Wellcome Trust/United Kingdom GR - R01 AI133673/AI/NIAID NIH HHS/United States GR - 110110/Z/15/Z/WT_/Wellcome Trust/United Kingdom GR - 109965MA/WT_/Wellcome Trust/United Kingdom GR - 110110/WT_/Wellcome Trust/United Kingdom GR - 268904/ERC_/European Research Council/International GR - 109965/WT_/Wellcome Trust/United Kingdom GR - 104748MA/WT_/Wellcome Trust/United Kingdom GR - 109965/Z/15/Z/WT_/Wellcome Trust/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190221 PL - England TA - BMC Med JT - BMC medicine JID - 101190723 RN - 0 (Hepatitis B Vaccines) SB - IM MH - Adolescent MH - Adult MH - Child MH - Cohort Studies MH - Coinfection/*epidemiology MH - Female MH - HIV Infections/*epidemiology/*prevention & control MH - Hepatitis B Vaccines/pharmacology/*therapeutic use MH - Humans MH - Infectious Disease Transmission, Vertical/*prevention & control MH - Middle Aged MH - Young Adult PMC - PMC6383254 OTO - NOTNLM OT - Africa OT - Antibodies OT - Elimination OT - Epidemiology OT - HIV OT - Hepatitis B virus OT - Immunisation OT - PMTCT OT - Sustainable Development Goals OT - Vaccination COIS- ETHICS APPROVAL AND CONSENT TO PARTICIPATE: Ethics approval was obtained from the Ethics Committee of the Faculty of Health Science, University of the Free State, Bloemfontein, South Africa (HIV Study Ref: ETOVS Nr 08/09 and COSAC Study Ref: ECUFS NR 80/2014), and from the Oxfordshire Research Ethics Committee A, ref 06/Q1604/12. Written consent for enrollment into the study was obtained from the child's parent/guardian. CONSENT FOR PUBLICATION: Not applicable. COMPETING INTERESTS: PCM is an Associate Editor for BMC Infectious Diseases and undertakes consultancy work for Immunocore. PUBLISHER'S NOTE: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. EDAT- 2019/02/23 06:00 MHDA- 2019/11/14 06:00 PMCR- 2019/02/21 CRDT- 2019/02/22 06:00 PHST- 2018/09/24 00:00 [received] PHST- 2019/01/22 00:00 [accepted] PHST- 2019/02/22 06:00 [entrez] PHST- 2019/02/23 06:00 [pubmed] PHST- 2019/11/14 06:00 [medline] PHST- 2019/02/21 00:00 [pmc-release] AID - 10.1186/s12916-019-1269-x [pii] AID - 1269 [pii] AID - 10.1186/s12916-019-1269-x [doi] PST - epublish SO - BMC Med. 2019 Feb 21;17(1):43. doi: 10.1186/s12916-019-1269-x.