Hepatitis B eradication: vaccine as a key player.

OBJECTIVE: Despite the availability of a highly effective and safe vaccine against hepatitis B virus (HBV) infection for 40 years, still almost 300 million persons are estimated to be chronically infected by this virus worldwide. The World Health Organization (WHO) has proposed a plan for hepatitis elimination by 2030. However, several factors, such as the reduction and limitation in vaccination campaigns or vaccine hesitancy (VH) in some regions of the World, might have played a role in limiting the worldwide coverage of hepatitis B prophylaxis. This review aims to describe which factors, such as VH, may be hampering the WHO 2030 goal for hepatitis B eradication. METHODS: The review describes the development and characteristics of the HBV vaccine, from the first plasma-derived to the recombinant one. Eventual limitations in its effectiveness and particularly VH were reviewed. RESULTS: The apparent pitfalls of the HBV vaccine, such as long-term effectiveness, vaccine-escape mutants, and adverse effects, were proven not to be a concern for this vaccine. However, VH persists and was even intensified by the COVID-19 pandemic. CONCLUSIONS: Many barriers still exist, such as vaccine availability, lack of awareness of the benefits of HBV vaccination, and VH. HBV VH seems to be eventually overcome in many settings with active education campaigns and information, stressing the importance of developing these strategies to achieve the 2030 goal of the WHO.

The Hepatitis B Virus Genotypes E to J: The Overlooked Genotypes.

Hepatitis B virus (HBV) genotypes E to J are understudied genotypes. Genotype E is found almost exclusively in West Africa. Genotypes F and H are found in America and are rare in other parts of the world. The distribution of genotype G is not completely known. Genotypes I and J are found in Asia and probably result from recombination events with other genotypes. The number of reported sequences for HBV genotypes E to J is small compared to other genotypes, which could impact phylogenetic and pairwise distance analyses. Genotype F is the most divergent of the HBV genotypes and is subdivided into six subgenotypes F1 to F6. Genotype E may be a recent genotype circulating almost exclusively in sub-Saharan Africa. Genotype J is a putative genotype originating from a single Japanese patient. The paucity of data from sub-Saharan Africa and Latin America is due to the under-representation of these regions in clinical and research cohorts. The purpose of this review is to highlight the need for further research on HBV genotypes E to J, which appear to be overlooked genotypes.

Hepatitis B Virus Genotype Study in West Africa Reveals an Expanding Clade of Subgenotype A4.

Hepatitis B virus (HBV) classification comprises up to 10 genotypes with specific geographical distribution worldwide, further subdivided into 40 subgenotypes, which have different impacts on liver disease outcome. Though extensively studied, the classification of subgenotype A sequences remains ambiguous. This study aimed to characterize HBV isolates from West African patients and propose a more advanced classification of subgenotype A. Fourteen HBV full-length genome sequences isolated from patients from The Gambia and Senegal were obtained and phylogenetically analyzed. Phylogenetic analysis of HBV genotype A sequences isolated from Senegalese and Gambian patients exhibited separate clusters from the other known and confirmed subgenotypes A (A1, A2, A6). Most of the sequences (10/14) clustered with an isolate from Cuba, reported as subgenotype A4 (supported by maximal bootstrap value). Four isolates from The Gambia and Senegal clustered separately from all other subgenotypes and samples sequenced in the study. Three of which from The Gambia, designated as an expanding clade of subgenotype A4, exhibited a mean inter-subgenotypic nucleotide divergence over the entire genome sequence higher than 4% in comparison with the other subgenotypes and the other isolates sequenced in the study, except with subgenotype A4 isolates (3.9%), and this was supported by a maximal bootstrap value. The last one from Senegal seemed to be an expanding subgenotype close to the new clade of A4. Amino acid analysis unveiled a novel motif specific to these isolates. This study revealed an expanding evolution of HBV subgenotype A and novel amino acid motifs. It also highlighted the need for a consensus regarding the analysis and classification of HBV sequences.

Prevalence and molecular characterization of hepatitis B virus infection in HIV-infected children in Senegal.

BACKGROUND AND AIMS: Sub-Saharan Africa (SSA) is the region with the most patients co-infected with the human immunodeficiency virus (HIV) and the hepatitis B virus (HBV) worldwide. However, few studies have focused on SSA children who are at a higher risk of developing a chronic infection than adults. Furthermore, children on first-line antiretroviral therapy (ART) including low genetic barrier drugs may develop both HBV and HIV resistance mutations. The aim of this work was to document HIV-HBV co-infection and to characterize the HBV isolates in children in Senegal. METHODS: This is a retrospective study of 613 children infected with HIV on ART or not. Dried blood spot (DBS) specimens were used to detect hepatitis B surface antigen (HBsAg) with a rapid diagnostic test (RDT). Confirmation of HBsAg status and hepatitis B e antigen (HBeAg) detection was performed on an automated platform using the chemiluminescence assay technology. HBV viral DNA was quantified by real-time polymerase chain reaction (PCR) and the preS1/preS2/HBsAg region was genotyped by nested PCR followed by sequencing using the Sanger technique. RESULTS: The prevalence of HIV-HBV co-infection was 4.1% (25/613). The median age of co-infected children was 13 years (2 years-16 years) and 40% (10/25) were girls. Almost all 19/20 (95%) were infected with HIV-1 and 79% (19/24) were treated with 3TC-based triple combination ART. The median duration of time on ART was 15 months (3 months-80 months). More than half of the children 53% (9/17) were experiencing HIV virologic failure and 75% (6/8) had at least one HIV-related resistance-associated mutation (RAM). Of the six children with resistance, none of the three administered treatments were effective on HIV. Of the 25 co-infected children, 82% (18/22) were HBeAg-positive, while the median HBV viral load (VL) was 6.20 log10 IU/mL (24/25 patients), and 62,5% (10/16) of the children had a persistent HBV viremia. Combination of ART was the only factor associated with HBV viremia persistence. Amplification was successful in 15 out of 16 patients (rate of 94%), and the ensuing phylogenetic analysis revealed that eight strains (53%) belonged to genotype A and seven (47%) to genotype E. HBV-related 3TC RAMs were uncovered in 20% of these patients (3/15). HBsAg escape mutations were found in 20% of the children (3/15). CONCLUSIONS: Our results showed a high level of drug resistance mutations to both HIV and HBV, a significant level of HBsAg escape mutations, HBV DNA persistence and HIV virologic failure in co-infected children in Senegal. The HBV genotypes found were A and E.

Analytical performance of eight rapid point-of-care tests routinely used for the detection of HBsAg in Burkina Faso: A cross-sectional study.

BACKGROUND: In limited resources countries, HBsAg-rapid diagnostic test (RDT) represents a good alternative for the diagnosis of hepatitis B virus (HBV) infection. Due to many factors that can influence their analytical performances, an evaluation with local biological samples before using on a large scale is recommended. OBJECTIVES: The aims of the study were: (i) to evaluate the analytical performance of eight commercial RDTs used in Burkina Faso for the detection of HBsAg using serum from blood donors, and (ii) to propose an algorithm using these RDTs based on their analytical performance. STUDY DESIGN: 109 HBsAg-positive and 216 HBsAg-negative samples were included in this evaluation. A modified version of the World Health Organization (WHO) algorithm for the detection of HBsAg was used as the gold standard. A pairwise combination of RDTs performance was done to choose the best diagnostic algorithm. RESULTS: All RDTs presented an excellent specificity (Sp) (≥99.0 %) except Accucare HBsAg® test. Sensitivity (Se) ranged from 90.8 % (95 % CI: 87.9-93.7) for Rapid Signal™ HBsAg to 92.8 % (95 % CI: 90.3-95.5) for SD BioLine® HBsAg and Artron® HBsAg. The pairwise combinations of the Se and Sp of RDTs showed no improvement in diagnostic performance. CONCLUSION: The RDTs evaluated in this study have good sensitivities and excellent specificities indicating their use in clinical practice and for HBV mass screening in Burkina Faso. However, their use should be monitored in the context of blood transfusion. Furthermore, according to our algorithm, each positive sample should be confirmed by another RDT of good Se.