Prevalence of HBsAg and HBeAg from 37 studies of HBV drug resistance in Africa.

<p>Prevalence of HBsAg and HBeAg from 37 studies of HBV drug resistance in Africa.</p

HBV drug resistance associated mutations (RAMs), vaccine escape mutations (VEMs) and mutations associated with Hepatitis B immunoglobulin (HBIg) resistance.

<p>HBV genes are shown in the coloured ovals. TDF = tenofovir, ETV = entecavir, 3TC = lamivudine. This figure incorporates data from eight studies; three were identified by the systematic review presented in this manuscript [<a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0006629#pntd.0006629.ref012" target="_blank">12</a>–<a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0006629#pntd.0006629.ref014" target="_blank">14</a>] and five from the wider literature [<a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0006629#pntd.0006629.ref007" target="_blank">7</a>,<a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0006629#pntd.0006629.ref015" target="_blank">15</a>–<a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0006629#pntd.0006629.ref018" target="_blank">18</a>].</p

Annotated map to summarise HBV drug resistance associated mutations (RAMs) and vaccine escape mutations (VEMs).

<p>Mutations identified from 33 studies of African cohorts published between 2007 and 2017 (inclusive). Four studies identified by our systematic literature review were not represented here as they did not report any RAMs. Full details of each citation can be found in <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0006629#pntd.0006629.t001" target="_blank">Table 1</a>.</p

Prevalence of HBV resistance associated mutations (RAMs) in Pol/RT proteins among HBV infected patients in Africa.

<p>These data are derived from 27 studies of HBV drug resistance in Africa published between 2007 and 2017 (inclusive). The countries represented are listed in alphabetical order. A detailed summary of RAMs identified from each study is presented (<a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0006629#pntd.0006629.g002" target="_blank">Fig 2</a>, <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0006629#pntd.0006629.s006" target="_blank">S4 Table</a>, <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0006629#pntd.0006629.s007" target="_blank">S5 Table</a>). Prevalence of RAMs for a specific country was determined by grouping all studies from that country that reported a specific mutation. We used all individuals who tested HBsAg positive to generate a denominator in order to provide a conservative estimate of RAM prevalence, and the numerator was the total number of individuals with that specific mutation from these studies. A: treatment naïve; B: treatment experienced.</p

HBV drug resistant mutations (RAMs) identified from HBV genome sequences from Africa downloaded from the Hepatitis B Virus database (https://hbvdb.ibcp.fr/) [36] and GenBank database (http://hvdr.bioinf.wits.ac.za/alignments/) [37].

<p>HBV drug resistant mutations (RAMs) identified from HBV genome sequences from Africa downloaded from the Hepatitis B Virus database (<a href="https://hbvdb.ibcp.fr/" target="_blank">https://hbvdb.ibcp.fr/</a>) [<a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0006629#pntd.0006629.ref036" target="_blank">36</a>] and GenBank database (<a href="http://hvdr.bioinf.wits.ac.za/alignments/" target="_blank">http://hvdr.bioinf.wits.ac.za/alignments/</a>) [<a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0006629#pntd.0006629.ref037" target="_blank">37</a>].</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

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

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

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