Hepatitis B virus infection as a neglected tropical disease

PCM is funded by a Wellcome Trust Intermediate Fellowship Grant (ref 110110/Z/15/Z).Publisher PDFPeer reviewe

Hepatitis B virus infection as a neglected tropical disease

PCM is funded by a Wellcome Trust Intermediate Fellowship Grant (ref 110110/Z/15/Z).Publisher PDFPeer reviewe

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

A package of interventions to move towards elimination of hepatitis B virus (HBV) infection as a public health threat.

<p>Suggested measures are aligned with WHO interventions for neglected tropical diseases (NTDs).</p

Resource gap in research funding allocations and academic publications for hepatitis B virus (HBV), hepatitis C virus (HCV), HIV, and malaria.

<p>Panels A/C: funding data from the United States National Institutes for Health (NIH) estimated funding for research, condition, and disease categories 2013–2018 (*projected figures for 2017 and 2018), available at <a href="https://report.nih.gov/categorical_spending.aspx" target="_blank">https://report.nih.gov/categorical_spending.aspx</a>, downloaded June 2017. For the projected funding allocation for 2018, HCV will receive 2.3-fold HBV funding, malaria 4.8-fold, and HIV 66.8-fold. Research into “malaria” and “malaria vaccine” are subdivided in the source data set but have been pooled in this graphic. Panels B/D: We recorded the number of publications listed on NCBI PubMed based on the search terms “HIV,” “HBV,” “HCV,” and “malaria” for each year from 2007–2016. Example search string for HBV publications in 2016: (HBV[Title]) AND ("2016/01/01"[Date—Publication]: "2016/12/31"[Date—Publication]). Data are represented as absolute numbers (panels A and B) and the proportion of the whole (panels C and D). For hepatitis delta virus (HDV), funding allocation data are not available, and we identified <25 publications/year (range 7–23).</p

The hepatitis B virus (HBV) cascade.

<p>Diagrammatic representation of the total burden of HBV infection and the subsets of individuals who are diagnosed (orange), linked to care (green), engaged with care (blue), on treatment (light purple), and have suppressed viremia (dark purple). An estimate of the proportion of cases undiagnosed versus diagnosed (91% versus 9%, respectively) is based on the WHO fact sheet [<a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0005842#pntd.0005842.ref003" target="_blank">3</a>]. The proportion who flow from each pool to the next is otherwise represented by a question mark, as these numbers are not represented by robust data.</p

Drug therapy used to treat HBV.

<p>Costing is based on the International Medical Products Price Guide: <a href="http://mshpriceguide.org/en" target="_blank">http://mshpriceguide.org/en</a> (data accessed May 2017. Price for lamivudine (3TC)—South Africa Department of Health; Price for tenofovir (TDF)—Supply Chain Management Project; price for HBV immunoglobulin (HBIG)—Sudan Medicins Sans Frontieres). WHO essential medicines: <a href="http://who.int/medicines/publications/essentialmedicines/EML_2015_FINAL_amended_NOV2015.pdf?ua=1" target="_blank">http://who.int/medicines/publications/essentialmedicines/EML_2015_FINAL_amended_NOV2015.pdf?ua=1</a>.</p