RT Journal Article
SR Electronic
T1 Can we meet global challenges for elimination of Hepatitis B Virus infection by 2030? Vaccine-mediated immunity in a South African cohort and a model of transmission and prevention
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 162594
DO 10.1101/162594
A1 Anna McNaughton
A1 José Lourenço
A1 Louise Hattingh
A1 Emily Adland
A1 Samantha Daniels
A1 Anriette van Zyl
A1 Connie S Akiror
A1 Susan Wareing
A1 Katie Jeffery
A1 Azim Ansari
A1 Paul Klenerman
A1 Philip J R Goulder
A1 Sunetra Gupta
A1 Pieter Jooste
A1 Philippa C Matthews
YR 2017
UL http://biorxiv.org/content/early/2017/11/09/162594.abstract
AB Background Sustainable Development Goals and the World Health Organisation (WHO) Global health sector strategy on viral hepatitis have set a challenge for the elimination of hepatitis B virus (HBV) infection as a public health concern by the year 2030. Based on current estimates of 250 million individuals with chronic infection, an intensive scale-up of interventions will be required. We set out to characterise the epidemiology of HBV infection and the prevalence of vaccine-mediated protection in a cohort of South African children, and used these data, alongside parameters from the published literature, to inform a model of HBV transmission and prevention. This has allowed us to develop evidence-based insights into the extent to which scaling up vaccination and prevention of mother-to-child transmission (PMTCT) might ultimately contribute to HBV elimination, and to assess the extent to which the targets for 2030 are realistic.Methods and findings We studied a cohort of 310 children (136 HIV-positive; 174 HIV-negative) aged 6-60 months in Kimberley, South Africa. Less than 1% of children in this setting were HBV infected (HBsAg positive). A vaccine-mediated antibody (anti-HBs) titre ≥10 mIU/ml was present in 238/310 children (77%). Anti-HBs titres were higher in HIV-negative children and in younger children (p<0.0001 in each case). Using these data, together with estimates of HBV transmission and epidemiology derived from the wider literature, we developed a model of HBV infection dynamics. We used this model to investigate the influence of prevention strategies, focusing on vaccination and PMTCT. Current vaccination efforts can be predicted to reduce population prevalence by ~20% in the first 25 years, but can bring the prevalence of HBV e-antigen (HBeAg)-positive chronic carriers down by ~40% in the same time period. We show likely additional benefit in providing catch-up vaccination in the short-term, but little long-term difference. Combining neonatal vaccination with robust PMTCT is the most effective population-level strategy to secure short-term impact, but coverage of both interventions needs to be high. Thus with strategies and resources already available, significant, positive public health impact is possible, although time to HBV elimination is likely to be substantially longer than that proposed by current goals.Conclusions At the level of an individual cohort, these data reflect the substantial overall success of HBV immunisation, with <1% of children now becoming infected with HBV in an endemic setting. However, we go on to demonstrate that to move towards the target of elimination, major improvements in vaccination deployment and coverage are required, and enhanced efforts in PMTCT. Realistic targets, rather than focusing on a complete elimination of the public health threat posed by HBV by the year 2030, may be better aiming for a substantial reduction in prevalence, which will come about through vaccination, PMTCT, and reduction of HBeAg-positive carriage. The magnitude of the elimination challenge, and the long time periods of sustained investment that will be required, underline the crucial importance of parallel investment into diagnostics, advocacy, policy, education and ongoing research into HBV cure strategies.