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. José Lourenço, Research Lecturer in Infectious Diseases Anna L McNaughton Sunetra Gupta Philippa C Matthews 4 th October 2018 / Peter Medawar day
HBV epidemiology and transmission
HBV epidemiology and transmission
HBV epidemiology and transmission stages of public health concern x Neonatal vaccination x PMTCT
HBV and HIV distributions in Africa Systematic literature HBV spatial variation by Anna McNaughton prevalence varies significantly across screened 880 studies, included 87 studies with the continent, but also within each 100 cohorts country HIV co-infection impaired HBV vaccine responses have been reported in HIV+ individuals Both aspects could be critical for efficient, local HBV control.
Context and motivation sustainable development goals (SDGs, set by WHO 2016) Lack of modelling frameworks in the literature supporting SDGs ► di ffi cult to understand where WHO’s SDGs come from ► HBV elimination as a public health threat by 2030 (worldwide) ► di ffi cult to understand what does it take to reach those SDGs ► 90% reduction in incidence (HBsAg, new cases) Nayagam et al. 2016 Lancet Infectious Diseases ► equivalent to 1 in 1000 HBV prevalence ► Does not assess WHO SDGs ► Does not assess impact on chronic prevalence ► no speci fi c targets on chronic incidence or prevalence (most ► Does not model possible effects of HIV relevant for public health) ► Was not designed to be easily fi t to a single population ► di ffi cult to link worldwide targets to regional case studies
We set out to... ► develop a region-speci fi c 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 Model + Cohort from South Africa.
Our (parsimonious) HBV framework PMTCT effect of HIV-status on vaccine protection routine neonatal vaccination catch-up or routine vaccination older ages
Kimberley, South African cohort cohort design This cohort is a snapshot of an Philip Goulder (Oxford) HBV vaccinated population, in Emily Adland (Oxford) which HBV and HIV infections Pieter Jooste (South Africa) are co-endemic cohort analyses HBV vaccine response is Anna McNaughton (Oxford) dependent on HIV serostatus. Philippa Matthews (Oxford)
HIV status and HBV vaccine response in age Cohort data and fi tting Data projection (A,B) Proportion individuals with vaccine response in age by HIV sero-status. (C) Vaccine response was (A,B) Data was fi t (using non-linear weighted least-squares). projected for unobserved ages. (A) (B) (C)
Model fi t, SDGs and impact projection.
Model fi t and calibration to Kimberley (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.
Projections and Sustainable Development Goals (SDGs) Progress towards SDGs can be measured: ► reduction relative to pre-intervention ► time it takes to reach an SDG WHO de fi nition 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
Mean, local potential of routine neonatal vaccination combined with PMTCT.
Neonate vaccination combined with PMTCT year to reach SDG of 90% reduction % reduction by 2030
Neonate vaccination combined with PMTCT year to reach SDG of WHO’s SDG of 90% incidence 90% reduction % reduction by 2030 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 e ffi cient at PMTCT.
Mean behaviour is reasonably positive, but what about the actual probability of achieving SDGs?
Example: projections of neonate routine vaccination projection variation both from parameter uncertainty and random effects (stochasticity) Progress towards SDGs can be measured: ► probability of reaching an SDG per year
Probability of achieving WHO’s SDG: incidence vs prevalence 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.
Probability of achieving WHO’s SDG: incidence vs prevalence SDG= 90% reduction HBV incidence SDGs based on HBV incidence are highly optimistic and hide the challenge of controlling Probability = 0.5 = results presented with colour maps (i.e. mean behaviour) chronic HBV prevalence. Certainty, i.e. probability ➜ 1, shows much longer time scales.
Probability of achieving WHO’s SDG in the context of HIV If local HIV prevalence ► would reduce to 0, time to SDG would decrease by ~4 years HIV prevalence has little impact on ► would increase x4, time to SDG would increase by ~10 years time of SDG achievement.
Probability of achieving WHO’s SDG using catch-up of older ages Catch-up campaigns on older age-groups Because a large proportion of the target population is do not reduce the time to achieve SDGs already infected or immune, and has an intrinsically low and will therefore not be cost-effective. probability of developing chronic infection (due to age).
In summary...
Summary of conclusions Region-speci fi c model to be informed by local cohort studies easily parameterized & fi t 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 signi fi cant, but are not signi fi cant for SDG achievement Older-age vaccination offers little bene fi t for SDG achievement and is likely not cost-effective Vaccination is working and plays a critical role for HBV control as a public health issue.
Special thanks to everyone involved in the two projects. Anna L McNaughton Anna L McNaughton José Lourenço José Lourenço Louise Hattingh Phillip A Bester Emily Adland Jolynne Mokaya Samantha Daniels Sheila F Lumley Anriette Van Zyl Donall Forde Connie S Akiror Tongai Maponga Susan Wareing Kenneth R Katumba Katie Jeffery Dominique Goedhals M Azim Ansari Sunetra Gupta Paul Klenerman Janet Seeley Philip J R Goulder Robert Newton Sunetra Gupta Ponsiano Ocama Pieter Jooste Philippa C Matthews Philippa C Matthews Department of Zoology Peter Medawar Building for Pathogen Research
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