NTDs “primarily affect populations living in tropical and subtropical areas”

Although HBV is endemic globally, the bulk of morbidity and mortality is now borne by low-/middle-income countries in tropical and subtropical regions [6,13]. In Africa, many populations are particularly vulnerable due to coendemic HIV infection and other coinfections, host and viral genetic factors, poverty, and lack of education and infrastructure [7]. In this setting, HBV has been eclipsed by the more acute and tangible health crisis of human immunodeficiency virus (HIV); only now in the era of antiretroviral therapy (ART) is it reemerging as a visible threat [S1 Supporting Information; case 2]. One illustration of this shift is the increase in deaths from HBV-related liver cancer over time that contrasts a reduction in AIDS deaths [14].

NTDs “disproportionately affect populations living in poverty and cause…morbidity and mortality, including stigma and discrimination”

HBV is part of a cycle of poverty, with a high burden of morbidity and mortality in young adults. The economic burden on individual families can be particularly catastrophic in low- and middle-income settings [15], although robust data are lacking for Africa. In resource-poor settings, lack of education and scarce healthcare resources impinge on successful diagnosis and monitoring as well as failure to control symptoms where relevant. Stigma and discrimination are often invisible but can be potent and highly relevant challenges to the success of scaling up interventions for prevention, diagnosis, and treatment [9] [S1 Supporting Information; cases 1, 4, 5, 6, 7, 9].

NTDs are “immediately amenable to broad control, elimination, or eradication by applying…public health strategies”

We already have an armamentarium of strategies with which to tackle HBV prevention and treatment (Fig 3). In order to be widely and robustly deployed, these approaches should interlink with existing resources and infrastructure wherever possible [S1 Supporting Information; case 2].

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Fig 3. A package of interventions to move towards elimination of hepatitis B virus (HBV) infection as a public health threat.

Suggested measures are aligned with WHO interventions for neglected tropical diseases (NTDs).

https://doi.org/10.1371/journal.pntd.0005842.g003

NTDs are “relatively neglected by research—i.e., resource allocation is not commensurate with the magnitude of the problem”

Compared with other blood-borne viruses, namely, HIV and hepatitis C virus, which infect substantially lower numbers [7], HBV has attracted far fewer research resources, and this gap may actually be widening over time [11,12] (Fig 2). A recent report of infectious diseases research investment in United Kingdom institutions documents that 0.7% of total expenditure is for HBV, compared to 3.0% for HCV, 13.9% for malaria, and 17.5% for HIV [12]. HBV mortality (887,000 deaths/year [3]) is now twice that of malaria (429,000 deaths/year [16]), but malaria receives nearly 5-fold more funding (Fig 2). Hepatitis delta virus (HDV), a copassenger with HBV, can drive aggressive liver disease but is almost completely overlooked in terms of resource allocation. Moreover, development of clinical programs for hepatitis testing and treatment are fragmented in comparison to the progressive infrastructure that has emerged to tackle HIV [S1 Supporting Information; case 7].

“Intensified case management”

Based on the significant numbers of individuals lost at every step of the “cascade” from diagnosis through to successful treatment and prevention (Fig 1), enhanced efforts are needed to promote linkage through care pathways. Enhanced HBV testing is crucial to facilitate entry into clinical care, allowing treatment to reduce the risk of onward spread, including underpinning PMTCT [S1 Supporting Information; case 8]. Initially, this may rely on using existing diagnostic platforms (based on serology), but investment is required in developing and rolling out new approaches, including molecular testing strategies that are more sensitive, provide enhanced data (e.g., detection of drug resistance), and are fast enough to enable point-of-care testing. This can often be transferred from technology that has been initially developed for the diagnosis of other diseases. Definitive curative therapy for HBV remains a crucial aspiration, as elimination using existing strategies is not realistic during the time frames set by SDGs [10]. Specifically, a therapeutic vaccine harnessing successful immune responses to boost immune clearance would provide a huge leap forward in tackling the existing burden of chronic infection [18].

The role and significance of stigma associated with HBV infection in Africa is largely unreported in the literature. However, individual testimony leaves no doubt that this is a significant barrier to diagnosis and clinical care [S1 Supporting Information; cases 5, 6]. Gaining a better understanding of the extent and nature of stigma and discrimination in different populations is a crucial first step, in parallel with enhanced efforts to educate patients, health care workers, and the public.

“Preventive chemotherapy”

Although antiviral therapy for HBV is generally regarded as treatment rather than prevention, in the majority of cases, it renders individuals aviremic, preventing onward transmission. Antiviral therapy for HBV (Table 1) should be made accessible, ideally capitalizing on the supply chains and distribution infrastructure that have been developed for HIV (and/or other prevalent infections, such as tuberculosis and malaria) [5]. Research efforts are still required to identify prognostic factors that predict differential response to therapy and allow tailoring of care.

PMTCT can progressively become a realistic goal by expanding access to antenatal diagnostics, simple treatment interventions such as maternal tenofovir during trimester 3, and HBV vaccination for all babies, with the first dose delivered at birth [8]. Vaccination remains a cornerstone of prevention, but more work is needed to investigate the most effective catch-up immunization strategies to reduce the burden of HBV infection at a population level [S1 Supporting Information; cases 3, 4, 8].

“Sanitation and hygiene”

Although this category of interventions is conventionally applied to reducing food- and waterborne infections, we here broaden our interpretation to include other aspects of prophylaxis. Safety and security of medical supplies has increasingly improved to reduce nosocomial transmission of blood-borne viruses over recent decades [S1 Supporting Information; case 3]. However, sterile practices need to be more widely promoted and guaranteed to assure the safety of other procedures such as scarification, tattoos, piercings, and circumcision that may occur in community settings. Provision of condoms alongside education regarding safe sex, particularly for high-risk groups such as sex workers and men who have sex with men, is another important strategy for prevention.