The role of HBV vaccination and prevention of mother to child - - PowerPoint PPT Presentation
The role of HBV vaccination and prevention of mother to child transmission as tools for elimination in the presence of HIV. Scrutiny from a model informed by a paediatric cohort in South Africa. Jos Loureno, Research Lecturer in Infectious
José Lourenço, Research Lecturer in Infectious Diseases Anna L McNaughton Sunetra Gupta Philippa C Matthews 4th October 2018 / Peter Medawar day
PMTCT Neonatal vaccination
stages of public health concern
HBV spatial variation prevalence varies significantly across the continent, but also within each country HIV co-infection impaired HBV vaccine responses have been reported in HIV+ individuals Both aspects could be critical for efficient, local HBV control.
Systematic literature by Anna McNaughton screened 880 studies, included 87 studies with 100 cohorts
Lack of modelling frameworks in the literature supporting SDGs ► difficult to understand where WHO’s SDGs come from ► difficult to understand what does it take to reach those SDGs Nayagam et al. 2016 Lancet Infectious Diseases ► Does not assess WHO SDGs ► Does not assess impact on chronic prevalence ► Does not model possible effects of HIV ► Was not designed to be easily fit to a single population
sustainable development goals (SDGs, set by WHO 2016)
► HBV elimination as a public health threat by 2030 (worldwide) ► 90% reduction in incidence (HBsAg, new cases) ► equivalent to 1 in 1000 HBV prevalence ► no specific targets on chronic incidence or prevalence (most relevant for public health) ► difficult to link worldwide targets to regional case studies
► develop a region-specific model to project local interventions informed by local cohort studies ► focus intervention impact and SDGs on chronic prevalence instead of incidence ► assess the effects of local HIV prevalence on SDGs
routine neonatal vaccination catch-up or routine vaccination older ages effect of HIV-status on vaccine protection PMTCT
cohort design Philip Goulder (Oxford) Emily Adland (Oxford) Pieter Jooste (South Africa) cohort analyses Anna McNaughton (Oxford) Philippa Matthews (Oxford) This cohort is a snapshot of an HBV vaccinated population, in which HBV and HIV infections are co-endemic HBV vaccine response is dependent on HIV serostatus.
Cohort data and fitting (A,B) Proportion individuals with vaccine response in age by HIV sero-status. (A,B) Data was fit (using non-linear weighted least-squares). Data projection (C) Vaccine response was projected for unobserved ages. (A) (B) (C)
(A1, A2) Model reproduced HBV pre-vaccination transmission (B) Unknown parameters had well behaved posteriors (C, D) Known parameters respected their priors Overall, output suggests model is robust to prior knowledge and can reproduce local transmission dynamics. We next simulated the introduction of interventions and measured progress towards SDGs.
Progress towards SDGs can be measured:
► reduction relative to pre-intervention ► time it takes to reach an SDG WHO definition of SDGs on “HBV elimination as a public health threat by 2030” ► 90% reduction in HBV incidence ► equivalent to 1 in 1000 prevalence which we apply to chronic infections
% reduction by 2030 year to reach SDG of 90% reduction
WHO’s SDG of 90% incidence reduction is achievable by 2030. For example, with combined 90% effort on PMTCT and vaccination. SDGs based on incidence are generally optimistic. Note: many underdeveloped countries are not efficient at PMTCT.
% reduction by 2030 year to reach SDG of 90% reduction
projection variation
both from parameter uncertainty and random effects (stochasticity) Progress towards SDGs can be measured:
► probability of reaching an SDG per year
SDG= 90% reduction HBV incidence
Probability = 0.5 = results presented with colour maps (i.e. mean behaviour) Certainty, i.e. probability ➜ 1, shows much longer time scales.
SDG= 90% reduction HBV incidence
Probability = 0.5 = results presented with colour maps (i.e. mean behaviour) Certainty, i.e. probability ➜ 1, shows much longer time scales.
SDGs based on HBV incidence are highly
chronic HBV prevalence.
If local HIV prevalence
► would reduce to 0, time to SDG would decrease by ~4 years ► would increase x4, time to SDG would increase by ~10 years
HIV prevalence has little impact on time of SDG achievement.
Catch-up campaigns on older age-groups do not reduce the time to achieve SDGs and will therefore not be cost-effective. Because a large proportion of the target population is already infected or immune, and has an intrinsically low probability of developing chronic infection (due to age).
Region-specific model to be informed by local cohort studies easily parameterized & fit to regional data, allowing to project local interventions & assess the impact of HIV SDGs on incidence versus chronic prevalence targets based on incidence can lead to optimistic outcomes, but critically distract attention from the importance of reducing chronic prevalence HBV eradication / elimination versus control eradication appears beyond reach & efforts should be focused instead on control Effects of HIV individual level are significant, but are not significant for SDG achievement Older-age vaccination
Vaccination is working and plays a critical role for HBV control as a public health issue.
Anna L McNaughton José Lourenço Louise Hattingh Emily Adland Samantha Daniels Anriette Van Zyl Connie S Akiror Susan Wareing Katie Jeffery M Azim Ansari Paul Klenerman Philip J R Goulder Sunetra Gupta Pieter Jooste Philippa C Matthews
Department of Zoology Peter Medawar Building for Pathogen Research
Anna L McNaughton José Lourenço Phillip A Bester Jolynne Mokaya Sheila F Lumley Donall Forde Tongai Maponga Kenneth R Katumba Dominique Goedhals Sunetra Gupta Janet Seeley Robert Newton Ponsiano Ocama Philippa C Matthews
Special thanks to everyone involved in the two projects.