Mapping Hepatitis B Virus Genotypes, Recombinant Genotypes and Sub- genotypes on the African continent from 1997 to 2021: A Systematic Review with Meta-Analysis

Kafeero, Hussein Mukasa; Ndagire, Dorothy; Ocama, Ponsiano; Kato, Charles Drago; Wampande, Eddie M.; Walusansa, Abdul; Kajumbula, Henry; Kateete, David Patrick; Ssenku, Jamilu E.; Sendagire, Hakim

doi:10.21203/rs.3.rs-1998327/v1

Cited by 3 publications

(5 citation statements)

References 91 publications

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“…Secondly, the risk factors to infection with HBV reported in our previous work have signi cantly differed between the low endemic and high endemic regions (43). For example, history of blood transfusion and familial contact with an HBV infected person were major risk factors for HBV infection in the low endemic region compared to the high endemic region (43). Thirdly, the HBsAB+/HBcAb+/HBeAb+ marker prevalenec rate was much higher among participnats from the high endemic region compared to those from the low endemic region (43).…”

Section: Discussionmentioning

confidence: 81%

“…Moreover, infection with a particular genotype presents with differences in infectivity and disease pro le (41) (42). Secondly, the risk factors to infection with HBV reported in our previous work have signi cantly differed between the low endemic and high endemic regions (43). For example, history of blood transfusion and familial contact with an HBV infected person were major risk factors for HBV infection in the low endemic region compared to the high endemic region (43).…”

Section: Discussionmentioning

confidence: 89%

“…For example, history of blood transfusion and familial contact with an HBV infected person were major risk factors for HBV infection in the low endemic region compared to the high endemic region (43). Thirdly, the HBsAB+/HBcAb+/HBeAb+ marker prevalenec rate was much higher among participnats from the high endemic region compared to those from the low endemic region (43). This is an indicator of immune escape mutation and higher infectivity (44).…”

Section: Discussionmentioning

confidence: 94%

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The wild type alleles at positions 857 and 1031 in the Tumor Necrosis Factor gene promoter are highly conserved among the low/high endemic HBV infected persons in Uganda and may not be attributable to disease burden.

Kafeero

Ndagire

Ocama

et al. 2022

Preprint

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Genetic polymorphisms within the gene loci of the promoter region of tumor necrosis factor (TNF) alpha have been associated with the pathogenesis of hepatitis B virus (HBV) infection. Moreover, the prevalence of these polymorphisms varies from individual to individual and are population specific. Thus, we aimed at testing the hypothesis that, TNF-α-863C/A and − 1031T/C polymorphic sites may have an effect on the difference in the burden of HBV in our country. We used a sample of 140 participants from both the low (70, 50%) and high (70, 50%) endemic regions. For each region, 35(50%) were HBsAg seropositive and 35(50%) were HBsAg seronegative. The HBsAg serostatus was evaluated by using the HBsAg Rapid Test Strip (Healgen Scientific Limited Liability Company, Houston, TX77047- USA) and confirmed by using the 5-panel HBV One Step Hepatitis B Virus Combo Test Device (FastepR, HBV-P43 M). For evaluation of the liver function parameters, the chemistry analyzer B120 (Mindray, China) was used. For the total DNA extraction, the QIAamp® DNA extraction kit was used following the manufactures guidelines. The PCR amplification of the extracted DNA was performed using Platinum Taq DNA Polymerase (Invitrogen Corporation, USA) to obtain a 450bp portion of the human TNF alpha promoter gene spanning position 862 and 1031. This was cleaned and sequenced by chain termination cycle sequencing using BigDye Terminator v3.1 (Applied Biosystems) following manufacturer’s guide lines. The cycle sequencing products were then cleaned with Big Dye X Terminator kit following the manufacturers guide line (Applied Biosystems). The NCBI HBV genotyping tool available at http://www.ncbi.nlm.nih.gov/projects/genotyping was used to determine the TNF-α-863C/A and TNF-α-863T/C genotype for each sequence. Pearson’s Chi-square and multinomial logistic were used for the analysis. All the analyses were done using SPSS version 26.0 and MedCalc software version 20.010 at 95% CI. A p < 0.05 was considered statistically significant. The HBsAg seropositive participants from the low and endemic region were significantly associated with elevation of both ALT and AST (p < 0.05). In contrast, only alanine aminotransferase (ALT) was significantly elevated among the HBsAg seropositive participants from the high endemic region (p < 0.05). The prevalence of Both the TNF-α-863C/A TNF-α-1031T/C genotypes and their alleles did not differ significantly among the study groups and by endemicity (p > 0.05). However, the prevalence of the nucleotide substitution mutations for TNF-α-863C > A and TNF-α-1031T > C was significantly low for all the study groups (p < 0.05). The conclusion from this research is that the TNF-α gene promoter is highly conserved in our population. Henceforth, the TNF-α-857C/A and 1031T/C polymorphisms may have no significant effects on the endemicity of HBV infection. Future research should focus on the use nationwide samples in order to come up with concreate decisions on the role of the TNF-α-polymorphisms in the risk/resolution of the HBV infections in an African or Negroid population.

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Section: Discussionmentioning

confidence: 81%

Section: Discussionmentioning

confidence: 89%

Section: Discussionmentioning

confidence: 94%

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The wild type alleles at positions 857 and 1031 in the Tumor Necrosis Factor gene promoter are highly conserved among the low/high endemic HBV infected persons in Uganda and may not be attributable to disease burden.

Kafeero

Ndagire

Ocama

et al. 2022

Preprint

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“…These genotypes have distinct geographic distribution [19], as do their sub‐genotypes, characterized by >3%–4% genomic nucleotide divergence [6, 20]. Accordingly, infection with different HBV genotypes and their related clinical outcomes are often highly associated with different ethnic populations [21–23].…”

Section: Discussionmentioning

confidence: 99%

Hepatitis B virus genotype surveillance in Canadian blood donors and a referred patient population, 2016–2021

Osiowy,

Giles,

Lowe

et al. 2023

Vox Sanguinis

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Background and ObjectivesHepatitis B virus (HBV) genotypes (A–H) have a distinct geographic distribution and are highly associated with the country of birth. Canada has experienced increased immigration over the past decade, primarily from regions where HBV is endemic. This study investigated the proportions and trends of HBV genotypes within blood donor and clinical populations of Canada over the period 2016–2021.Materials and MethodsStudy samples involved two cohorts: (1) Canadian blood donors (n = 246) deferred from donation due to HBV test positivity and (2) chronic HBV patients from across Canada (clinically referred population, n = 3539). Plasma or serum was extracted, and the surface antigen and/or polymerase‐coding region was amplified and sequenced to determine genotype by phylogenetic analysis.ResultsSix (A–E, G) and eight (A–H) HBV genotypes were detected among deferred blood donors and the clinically referred population, respectively. Differences in HBV genotype proportions between the two cohorts were observed across Canada. Males comprised most of the referred population among genotypes A–E (p < 0.0001), except for genotypes B and C. The median age was younger among blood donors (36 years [range 17–72]) compared with the referred population (41 years [range 0–99]). Distinct trends of increasing (E, referred; B, blood donor) and decreasing genotype prevalence were observed over the study period.ConclusionHBV genotypes in Canada are highly diverse, suggesting a large immigrant population. Observed trends in genotype prevalence and proportional differences among cohorts imply shifts among the HBV‐infected population of Canada, which warrants continued surveillance.

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“…Nevertheless, the fact that HBV recombinants have been so widely and increasingly detected suggests that the recombinants detected here are likely accurate. Genotype B/E recombinants identified in Eritria are the most common in Africa [35]. Genotype D/E recombinants are also common, having been identified in eight countries, namely Kenya, Niger, Egypt, Ghana, Libya, Mali, Eritria, and Uganda [35], followed by genotype A/E, identified in five countries, namely Uganda, Eretria, Ghana, Niger, and Mozambique [35,36],…”

Section: Mcnaughton Et Al Developed a Sequencing Protocol Utilizing R...mentioning

confidence: 99%

An Oxford Nanopore Technology-Based Hepatitis B Virus Sequencing Protocol Suitable For Genomic Surveillance Within Clinical Diagnostic Settings

Tshiabuila,

Choga,

James

et al. 2024

Preprint

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Chronic hepatitis B virus (HBV) infection remains a significant public health concern, particularly in Africa, where there is a substantial substantial. HBV is an enveloped virus, with isolates being classified into ten phylogenetically distinct genotypes (A-J) determined based on full-genome sequence data or reverse hybridization-based diagnostic tests. In practice, limitations are noted in that diagnostic sequencing, generally using Sanger sequencing, tends to focus only on the S-gene, yielding little or no information on intra-patient HBV genetic diversity with very low-frequency variants and reverse hybridization detects only known genotype-specific mutations. To resolve these limitations, we developed an Oxford Nanopore Technology (ONT)-based HBV genotyping protocol suitable for clinical virology, yielding complete HBV genome sequences and extensive data on intra-patient HBV diversity. Specifically, the protocol involves tiling-based PCR amplification of HBV sequences, library preparation using the ONT Rapid Barcoding Kit, ONT GridION sequencing, genotyping using Genome Detective software, recombination analysis using jpHMM and RDP5 software, and drug resistance profiling using Geno2pheno software. We prove the utility of our protocol by efficiently generating and characterizing high-quality near full-length HBV genomes from 148 left-over diagnostic Hepatitis B patient samples obtained in the Western Cape province of South Africa, providing valuable insights into the genetic diversity and epidemiology of HBV in this region of the world.

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Mapping Hepatitis B Virus Genotypes, Recombinant Genotypes and Sub- genotypes on the African continent from 1997 to 2021: A Systematic Review with Meta-Analysis

Cited by 3 publications

References 91 publications

The wild type alleles at positions 857 and 1031 in the Tumor Necrosis Factor gene promoter are highly conserved among the low/high endemic HBV infected persons in Uganda and may not be attributable to disease burden.

The wild type alleles at positions 857 and 1031 in the Tumor Necrosis Factor gene promoter are highly conserved among the low/high endemic HBV infected persons in Uganda and may not be attributable to disease burden.

Hepatitis B virus genotype surveillance in Canadian blood donors and a referred patient population, 2016–2021

An Oxford Nanopore Technology-Based Hepatitis B Virus Sequencing Protocol Suitable For Genomic Surveillance Within Clinical Diagnostic Settings

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