People from low- and middle-income countries are disproportionately affected by the global burden of adverse health effects caused by ambient air pollution (AAP). However, data from Sub-Saharan Africa (SSA) are still scarce. We systematically reviewed the literature to describe the existing knowledge on AAP and health outcomes in SSA. We searched PubMed, Medline-OVID, EMBASE and Scopus databases to identify studies of AAP and health outcomes published up to November 15, 2017. We used a systematic review approach to critically analyze and summarize levels of outdoor air pollutants, and data on health effects associated with AAP. We excluded occupational and indoor exposure studies. We identified 60 articles, with 37 only describing levels of AAP and 23 assessing the association between air pollution and health outcomes. Most studies (75%) addressing the relation between AAP and disease were cross-sectional. In general, exposure data were only obtained for selected cities in the framework of temporary international collaborative research initiatives without structural long-term continuation. Measurements of AAP revealed 10-20 fold higher levels than WHO standards. Of the 23 studies reporting health effects, 14 originated from South Africa, and most countries within SSA contributed no data at all. No studies, except from South Africa, were based on reliable morbidity or mortality statistics at regional or country level. The majority of studies investigated self-reported respiratory symptoms. Children and the elderly were found to be more susceptible to AAP. AAP and its negative health effects have been understudied in SSA compared with other continents. The limited direct measurements of air pollutants indicate that AAP in SAA cities is high compared with international standards. Efforts are needed to monitor AAP in African cities, to identify its main sources, and to reduce adverse health effects by enforcing legislation.

Advancing interventions to tackle the huge global burden of hepatitis B virus (HBV) infection depends on improved insights into virus epidemiology, transmission, within-host diversity, drug resistance and pathogenesis, all of which can be advanced through the large-scale generation of full-length virus genome data. Here we describe advances to a protocol that exploits the circular HBV genome structure, using isothermal rolling-circle amplification to enrich HBV DNA, generating concatemeric amplicons containing multiple successive copies of the same genome. We show that this product is suitable for Nanopore sequencing as single reads, as well as for generating short-read Illumina sequences. Nanopore reads can be used to implement a straightforward method for error correction that reduces the per-read error rate, by comparing multiple genome copies combined into a single concatemer and by analysing reads generated from plus and minus strands. With this approach, we can achieve an improved consensus sequencing accuracy of 99.7% and resolve intra-sample sequence variants to form whole-genome haplotypes. Thus while Illumina sequencing may still be the most accurate way to capture within-sample diversity, Nanopore data can contribute to an understanding of linkage between polymorphisms within individual virions. The combination of isothermal amplification and Nanopore sequencing also offers appealing potential to develop point-of-care tests for HBV, and for other viruses.

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

Background: The Global Hepatitis Health Sector Strategy is aiming for the elimination of viral hepatitis as a public health threat by 2030. Successful diagnostic, treatment and preventive strategies can reduce incidence and morbidity; it is important to ensure that these interventions and services are not only available, but also accessible. Stigma, poverty, and lack of knowledge may present a substantial barrier, especially in resource limited settings. We therefore set out to assimilate evidence for the nature and impact of stigma on the lives of people with HBV infection and on the community, and to suggest ways to tackle stigma and discrimination. Methods: We carried out a literature search in PubMed using the search terms ‘hepatitis B’, ‘stigma’ to identify relevant papers published between 2007 and 2017 (inclusive), with a particular focus on Africa. Results: We identified a total of 34 articles, of which only one study was conducted in Africa. Lack of knowledge on HBV was consistently identified: there were misconceptions about HBV transmission among the public, healthcare workers (HCWs) provided inaccurate information to individuals diagnosed with HBV, and poor understanding resulted in lack of preventive precautions. Stigma negatively impacted on health behaviour such as help-seeking, screening, disclosure, prevention of transmission, and adherence to treatment. Conclusion: Stigma is a potentially major barrier to the successful implementation of preventive, diagnostic and treatment strategies for HBV infection, and yet there is very limited recognition of the magnitude of this challenge, especially in Africa. There is a need for more research in this area, to identify and evaluate interventions that can be used effectively to tackle stigma in HBV, and to inform collaborative efforts between policy makers, HCWs, traditional healers, religious leaders, charity organisations and support groups, to improve awareness and tackle stigma in HBV in Africa.

International Sustainable Development Goals (SDGs) for elimination of hepatitis B virus (HBV) infection set ambitious targets for 2030. In African populations, infant immunisation has been fundamental to reducing incident infections in children, but overall population prevalence of chronic hepatitis B (CHB) infection remains high. In high-prevalence populations, adult catch-up vaccination has sometimes been deployed, but an alternative Test and Treat (T&T) approach could be used as an intervention to interrupt transmission. Universal T&T has not been previously evaluated as a population intervention for HBV infection, despite high-profile data supporting its success with human immunodeficiency virus (HIV). We set out to investigate the relationship between prevalence of HBV infection and exposure in Africa, undertaking a systematic literature review in November 2019. We identified published seroepidemiology data representing the period 1995–2019 from PubMed and Web of Science, including studies of adults that reported prevalence of both hepatitis B surface antigen (HBsAg; prevalence of HBV infection) and antibody to hepatitis B core antigen (anti-HBc; prevalence of HBV exposure). We identified 96 studies representing 39 African countries, with a median cohort size of 370 participants and a median participant age of 34 years. Using weighted linear regression analysis, we found a strong relationship between the prevalence of infection (HBsAg) and exposure (anti-HBc) (R² = 0.45, p < 0.001). Region-specific differences were present, with estimated CHB prevalence in Northern Africa typically 30% to 40% lower (p = 0.007) than in Southern Africa for statistically similar exposure rates, demonstrating the need for intervention strategies to be tailored to individual settings. We applied a previously published mathematical model to investigate the effect of interventions in a high-prevalence setting. The most marked and sustained impact was projected with a T&T strategy, with a predicted reduction of 33% prevalence by 20 years (95% CI 30%–37%) and 62% at 50 years (95% CI 57%–68%), followed by routine neonatal vaccination and prevention of mother to child transmission (PMTCT; at 100% coverage). In contrast, the impact of catch-up vaccination in adults had a negligible and transient effect on population prevalence. The study is constrained by gaps in the published data, such that we could not model the impact of antiviral therapy based on stratification by specific clinical criteria and our model framework does not include explicit age-specific or risk-group assumptions regarding force of transmission. The unique data set collected in this study highlights how regional epidemiology data for HBV can provide insights into patterns of transmission, and it provides an evidence base for future quantitative research into the most effective local interventions. In combination with robust neonatal immunisation programmes, ongoing PMTCT efforts, and the vaccination of high-risk groups, diagnosing and treating HBV infection is likely to be of most impact in driving advances towards elimination targets at a population level.

International sustainable development goals for the elimination of viral hepatitis as a public health problem by 2030 highlight the pressing need to optimize strategies for prevention, diagnosis and treatment. Selected or transmitted resistance associated mutations (RAMs) and vaccine escape mutations (VEMs) in hepatitis B virus (HBV) may reduce the success of existing treatment and prevention strategies. These issues are particularly pertinent for many settings in Africa where there is high HBV prevalence and co-endemic HIV infection, but lack of robust epidemiological data and limited education, diagnostics and clinical care. The prevalence, distribution and impact of RAMs and VEMs in these populations are neglected in the current literature. We therefore set out to assimilate data for sub-Saharan Africa through a systematic literature review and analysis of published sequence data, and present these in an on-line database (https://livedataoxford.shinyapps.io/1510659619-3Xkoe2NKkKJ7Drg/). The majority of the data were from HIV/HBV coinfected cohorts. The commonest RAM was rtM204I/V, either alone or in combination with associated mutations, and identified in both reportedly treatment-naïve and treatment-experienced adults. We also identified the suite of mutations rtM204V/I + rtL180M + rtV173L, that has been associated with vaccine escape, in over 1/3 of cohorts. Although tenofovir has a high genetic barrier to resistance, it is of concern that emerging data suggest polymorphisms that may be associated with resistance, although the precise clinical impact of these is unknown. Overall, there is an urgent need for improved diagnostic screening, enhanced laboratory assessment of HBV before and during therapy, and sustained roll out of tenofovir in preference to lamivudine alone. Further data are needed in order to inform population and individual approaches to HBV diagnosis, monitoring and therapy in these highly vulnerable settings. The Global Hepatitis Health Sector Strategy is aiming for the elimination of viral hepatitis as a public health threat by 2030. However, mutations associated with drug resistance and vaccine escape may reduce the success of existing treatment and prevention strategies. In the current literature, the prevalence, distribution and impact of hepatitis B virus (HBV) mutations in many settings in Africa are neglected, despite the high prevalence of HBV and co-endemic HIV infection. This systematic review describes the frequency, prevalence and co-occurrence of mutations associated with HBV drug resistance and vaccine escape mutations in Africa. The findings suggest a high prevalence of these mutations in some populations in sub-Saharan Africa. Scarce resources have contributed to the lack of HBV diagnostic screening, inconsistent supply of drugs, and poor access to clinical monitoring, all of which contribute to drug and vaccine resistance. Sustainable long-term investment is required to expand consistent drug and vaccine supply, to provide screening to diagnose infection and to detect drug resistance, and to provide appropriate targeted clinical monitoring for treated patients.