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

Abstract

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. Electronic supplementary material The online version of this article (10.1186/s12916-019-1269-x) contains supplementary material, which is available to authorized users.

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

“…In this study, we adapted a previously published HBV dynamic model and Markov chain Monte Carlo (MCMC) approach that we initially developed to fit the seroepidemiology of Kimberley in South Africa to project the impact of interventions in that transmission setting [9]; as our mathematical and computational methods are already published, we have not replicated them in this paper. However, for ease of reference, we have provided a summary overview of model population classes in Fig 2, as well as relevant parameters in S1 Table. In this instance, we fitted the model to data from Uganda, a setting of high HBsAg prevalence [3].…”

“…Vaccination is included in the Expanded Programme for Immunization (EPI) and has been progressively rolled out for infants across Africa since 1995, alongside enhanced interventions for the prevention of mother to child transmission (PMTCT) [8]. However, despite 2 decades of vaccine implementation, CHB remains endemic in many regions, and published mathematical models exploring the impact of existing interventions demonstrate time scales for success that are substantially beyond the 2030 targets [9,10].…”

“…There is an interesting conflict between formal recommendations and public health policies that are deployed in practice. Although evidence suggests that 'catch-up' vaccination campaigns are likely to have limited population benefit [9] and are not endorsed by guidelines [8], the strategy can appear an attractive public health approach for older children and adults in high-prevalence populations [16] and has been undertaken in some settings [17]. Economic analyses have reported that catch-up campaigns in young adults are cost-effective only if combined with screening [18], highlighting the importance of focusing not only on prevention but also on investment in diagnosis and treatment [19].…”

“…We used a systematic literature review to investigate the seroepidemiology of HBV across the African subcontinent in order to highlight regional differences and inform local strategies, with a specific focus on interventions that target adults. Recognising that catch-up campaigns are already being deployed in some locations, we considered the evidence for any benefit of this approach, and in parallel, we assessed the impact of universal T&T using epidemiological data and a mathematical model [9].…”

Hepatitis B prevention: Can we learn from the response to HIV/AIDS?

“…McNaughton and colleagues used a mathematical model [3] to assess impact of test-andtreat strategies. These are inspired by the strategy of treatment as prevention for HIV, which has become one of the main pillars for HIV prevention in resource-limited settings [4].…”