HBV vaccination and PMTCT as elimination tools in the presence of HIV: insights from a clinical cohort and dynamic model.


Journal

BMC medicine
ISSN: 1741-7015
Titre abrégé: BMC Med
Pays: England
ID NLM: 101190723

Informations de publication

Date de publication:
21 02 2019
Historique:
received: 24 09 2018
accepted: 22 01 2019
entrez: 22 2 2019
pubmed: 23 2 2019
medline: 14 11 2019
Statut: epublish

Résumé

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. 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. 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. 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.

Sections du résumé

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.

Identifiants

pubmed: 30786896
doi: 10.1186/s12916-019-1269-x
pii: 10.1186/s12916-019-1269-x
pmc: PMC6383254
doi:

Substances chimiques

Hepatitis B Vaccines 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

43

Subventions

Organisme : Wellcome Trust
ID : 104748
Pays : United Kingdom
Organisme : NIAID NIH HHS
ID : R01 AI133673
Pays : United States
Organisme : Wellcome Trust
ID : 110110/Z/15/Z
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 109965MA
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 110110
Pays : United Kingdom
Organisme : European Research Council
ID : 268904
Pays : International
Organisme : Wellcome Trust
ID : 109965
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 104748MA
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 109965/Z/15/Z
Pays : United Kingdom

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Auteurs

Anna L McNaughton (AL)

Nuffield Department of Medicine, Peter Medawar Building for Pathogen Research, South Parks Road, Oxford, OX1 3SY, UK.

José Lourenço (J)

Department of Zoology, Peter Medawar Building for Pathogen Research, South Parks Road, Oxford, OX1 3SY, UK.

Louise Hattingh (L)

Department of Paediatrics, Kimberley Hospital, Kimberley, 8300, South Africa.

Emily Adland (E)

Department of Paediatrics, Peter Medawar Building for Pathogen Research, South Parks Road, Oxford, OX1 3SY, UK.

Samantha Daniels (S)

Department of Paediatrics, Kimberley Hospital, Kimberley, 8300, South Africa.

Anriette Van Zyl (A)

Department of Paediatrics, Kimberley Hospital, Kimberley, 8300, South Africa.

Connie S Akiror (CS)

Global Healthcare Public Foundation, Makindu Lane, Kololo, Kampala, Uganda.

Susan Wareing (S)

Department of Infectious Diseases and Microbiology, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Headley Way, Oxford, OX3 9DU, UK.

Katie Jeffery (K)

Department of Infectious Diseases and Microbiology, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Headley Way, Oxford, OX3 9DU, UK.

M Azim Ansari (MA)

Nuffield Department of Medicine, Peter Medawar Building for Pathogen Research, South Parks Road, Oxford, OX1 3SY, UK.

Paul Klenerman (P)

Nuffield Department of Medicine, Peter Medawar Building for Pathogen Research, South Parks Road, Oxford, OX1 3SY, UK.
Department of Infectious Diseases and Microbiology, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Headley Way, Oxford, OX3 9DU, UK.

Philip J R Goulder (PJR)

Department of Paediatrics, Peter Medawar Building for Pathogen Research, South Parks Road, Oxford, OX1 3SY, UK.

Sunetra Gupta (S)

Department of Zoology, Peter Medawar Building for Pathogen Research, South Parks Road, Oxford, OX1 3SY, UK.

Pieter Jooste (P)

Department of Paediatrics, Kimberley Hospital, Kimberley, 8300, South Africa.

Philippa C Matthews (PC)

Nuffield Department of Medicine, Peter Medawar Building for Pathogen Research, South Parks Road, Oxford, OX1 3SY, UK. philippa.matthews@ndm.ox.ac.uk.
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.

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