Genotyping and molecular characterization of hepatitis B virus in liver disease patients in Kenya

Ochwoto, Missiani; Chauhan, Richa; Gopalakrishnan, Deepak; Chen, Chien‐Yu; Ng’ang’a, Zipporah; Okoth, Fredrick; Kioko, Henry; Kimotho, James; Kaiguri, Peter; Kramvis, Anna

doi:10.1016/j.meegid.2013.08.013

Cited by 32 publications

(42 citation statements)

References 53 publications

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“…This finding is consistent with the identified intermediate to low prevalence of HBV among blood donors, and the single major clade with a common ancestor formed by the strains from all regions of the country. Genotype D has been reported from neighboring countries and from pregnant HIV positive women in Kigali City, however the country of origin of these women was not reported [31, 32]. In this study there were few serum samples from HBsAg positive blood donors from Kigali City, therefore other HBV genotypes may be present in the capital of Rwanda, even if they were not identified in this study.…”

Section: Discussionmentioning

confidence: 64%

Hepatitis B virus strains from Rwandan blood donors are genetically similar and form one clade within subgenotype A1

et al. 2017

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BackgroundRwanda is a central African country with about 12 million inhabitants. The 1994 genocide against the Tutsi destroyed much of the infrastructure, including the health system. Although this has improved significantly, many challenges remain to be addressed. In this study, the prevalence of serological markers of past and ongoing hepatitis B virus (HBV) infection and HBV vaccine related immunity was investigated in samples from blood donors from all regions of Rwanda.MethodsThe results from hepatitis B surface antigen (HBsAg) analyses of all (45,061) blood donations collected countrywide in 2014 from 13,637 first time and 31,424 repeat blood donors were compiled. Samples from 581 HBsAg negative blood donors were selected for further analysis for antibodies against HBV, anti-HBs and anti-HBc. Additional 139 samples from HBsAg positive donors were analyzed for HBeAg/anti-HBe (132 samples) and for HBV DNA. The S-gene was amplified by PCR, products sequenced, and phylogenetic analysis was performed.ResultsHBsAg was found in 4.1% of first time donors with somewhat higher prevalence among those from the Central and Eastern regions than from other parts of the country. Indications of past infection was found in 21% of the HBsAg negative donors, 4.3% had only anti-HBs suggesting HBV vaccination. HBeAg was detected in 28 (21%), anti-HBe in 97 (73%), and both HBeAg and anti-HBe in 4 of 132 HBsAg positive donors. HBV DNA was found in 85 samples, and the complete S-gene was sequenced in 58 of those. Phylogenetic analysis of the sequences revealed that all HBV strains belonged to subgenotype A1, and formed one clade in the phylogenetic tree. In addition, 12 strains from first time donors had a unique 18 amino acid deletion in the N-terminal part of the pre-S2 region.ConclusionThis study indicated that the prevalence of hepatitis B is intermediate in Rwanda and that the vaccination coverage is relatively low in young adults. All surveyed Rwandan blood donors were infected with similar subgenotype A1 strains, and a high frequency of those with anti-HBe had detectable HBV DNA. Several strains had in addition a unique pre-S2 deletion, the virulence of which needs to be further studied.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-016-2149-z) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 64%

Hepatitis B virus strains from Rwandan blood donors are genetically similar and form one clade within subgenotype A1

et al. 2017

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“…One clade is mainly ‘African’ and includes isolates from southern, eastern and central Africa, while the other, comprising isolates from Asia and Somalia, has been called ‘Asian’ [45]–[47] or ‘Afro-Asian’ [48]. Recently, the term ‘Asian-American’ has also been used to design this latter clade, based on phylogenetic analyses that included HBV/A1 isolates from Caribbean islands and a restricted number of South American strains [19], [31].…”

Section: Resultsmentioning

confidence: 99%

Hepatitis B Virus Subgenotype A1: Evolutionary Relationships between Brazilian, African and Asian Isolates

et al. 2014

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Brazil is a country of low hepatitis B virus (HBV) endemicity in which the genotype A of HBV (HBV/A) is the most prevalent. The complete nucleotide sequences of 26 HBV/A isolates, originating from eight Brazilian states, were determined. All were adw2. Twenty-three belonged to subgenotype A1 and three to A2. By phylogenetic analysis, it was shown that all the 23 HBV/A1 isolates clustered together with isolates from Bangladesh, India, Japan, Nepal, the Philippines and United Arab Emirates, but not with those of Congo, Kenya, Malawi, Rwanda, South Africa, Tanzania, Uganda and Zimbabwe. Four amino acid residues in the polymerase (His138 in the terminal protein domain, Pro18 and His90 in the spacer, and Ser109 in the reverse transcriptase), and one (Phe17) in the precore region, predominated in Latin American and Asian HBV/A1 isolates, but were rarely encountered in African isolates, with the exception of those from Somalia. Specific variations of two adjacent amino acids in the C-terminal domain of the HBx protein, namely Ala146 and Pro147, were found in all the Brazilian, but rarely in the other HBV/A1 isolates. By Bayesian analysis, the existence of an ‘Asian-American’ clade within subgenotype A1 was supported by a posterior probability value of 0.996. The close relatedness of the Brazilian, Asian and Somalian isolates suggests that the HBV/A1 strains predominant in Brazil did not originate from the five million slaves who were imported from Central and Western Africa from 1551 to 1840, but rather from the 300–400,000 captives forcibly removed from southeast Africa at the middle of the 19th century.

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“…Genotype A was the major circulating genotype, followed by genotype D, which was primarily observed in western regions of Kenya. Earlier Kenyan studies had observed genotypes D and E, with both subgenotypes D4 and D6 in circulation among blood donor and liver patients, respectively [ 6 , 7 , 14 ]. In this study, several recombinant HBV D/E variants were observed in western Kenya, with recombination breakpoints falling within the preS coding region.…”

Section: Discussionmentioning

confidence: 99%

“…HBV genotype E (HBV/E) is confined to West, Central and North Eastern Africa [ 5 , 13 ]. It has low genetic diversity with no identified subgenotypes but it is often associated with recombinant variants including genotypes D and A. Kenya is a large country at the geographical junction of the distribution of the three HBV genotypes A, D and E; however, little is known about the molecular diversity of HBV in Kenya apart from analysis of the basal core promoter/precore (BCP/PC) and partial preS2/S regions [ 6 , 7 , 14 ].…”

Section: Introductionmentioning

confidence: 99%

Hepatitis B infection is highly prevalent among patients presenting with jaundice in Kenya

et al. 2016

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BackgroundViral hepatitis is a major concern worldwide, with hepatitis A (HAV) and E (HEV) viruses showing sporadic outbreaks while hepatitis B (HBV) and C (HCV) viruses are associated with chronic hepatitis, cirrhosis and hepatocellular carcinoma. The present study determined the proportion, geographic distribution and molecular characterization of hepatitis viruses among patients seeking medical services at hospitals throughout Kenya.MethodsPatients presenting with jaundice at four selected hospitals were recruited (n = 389). Sera were tested for the presence of antibody to hepatitis viruses A through E, and HBV surface antigen (HBsAg). Nucleic acid from anti-HAV IgM antibody and HBsAg positive samples was extracted, amplified and sequenced.ResultsChronic HBV infection was the leading cause of morbidity among patients with symptoms of liver disease seeking medical help. Incident HCV, HEV and HDV infection were not detected among the patients in this study, while the proportion of acute HAV was low; HAV IgM positivity was observed in 6.3 % of patients and sequencing revealed that all cases belonged to genotype 1B. HCV seropositivity upon initial screening was 3.9 % but none were confirmed positive by a supplementary immunoblot assay. There was no serological evidence of HDV and acute HEV infection (anti-HEV IgM). HBsAg was found in 50.6 % of the patients and 2.3 % were positive for IgM antibody to the core protein, indicating probable acute infection. HBV genotype A was predominant (90.3 %) followed by D (9.7 %) among HBV DNA positive specimens. Full genome analysis showed HBV/D isolates having similarity to both D4 and D6 subgenotypes and D/E recombinant reference sequences. Two recombinant sequences demonstrated > 4 % nucleotide divergence from other previously known D/E recombinants.ConclusionsHBV is highly prevalent among patients seeking care for symptoms consistent with hepatitis, compared to the general population. Molecular characterization of HBV isolates indicated recombinant strains that may give rise to new circulating variants. There is a need to document the prevalence, clinical manifestation and distribution of the variants observed. HAV genotype 1B, prevalent in Africa, was observed; however, the absence of HCV, HDV and acute HEV in this study does not rule out their presence in Kenya.

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Genotyping and molecular characterization of hepatitis B virus in liver disease patients in Kenya

Cited by 32 publications

References 53 publications

Hepatitis B virus strains from Rwandan blood donors are genetically similar and form one clade within subgenotype A1

Hepatitis B virus strains from Rwandan blood donors are genetically similar and form one clade within subgenotype A1

Hepatitis B Virus Subgenotype A1: Evolutionary Relationships between Brazilian, African and Asian Isolates

Hepatitis B infection is highly prevalent among patients presenting with jaundice in Kenya

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