title: Disparate distribution of hepatitis B virus genotypes in four sub-Saharan African countries.
abstract: BACKGROUND
  Hepatitis B virus (HBV) places a substantial health burden on Africa. Here, we investigated genetic diversity of HBV variants circulating in 4 countries of sub-Saharan Africa using archived samples. In total, 1492 plasma samples were tested from HIV-infected individuals and pregnant women, among which 143 (9.6%) were PCR-positive for HBV DNA (Côte d'Ivoire, 70/608 [11.5%]; Ghana, 13/444 [2.9%]; Cameroon, 33/303 [10.9%]; and Uganda, 27/137 [19.7%]).
  
  
  RESULTS
  Phylogenetic analysis of the S-gene sequences identified HBV genotypes E (HBV/E, n=96) and A (HBV/A, n=47) distributed as follows: 87% of HBV/E and 13% of HBV/A in Côte d'Ivoire; 100% of HBV/E in Ghana; 67% of HBV/E and 33% of HBV/A in Cameroon; and 100% of HBV/A in Uganda. The average and maximal nucleotide distances among HBV/E sequences were 1.9% and 6.4%, respectively, suggesting a greater genetic diversity for this genotype than previously reported (p<0.001). HBV/A strains were classified into subgenotypes HBV/A1, HBV/A2 and HBV/A3. In Uganda, 93% of HBV/A strains belonged to HBV/A1 whereas HBV/A3 was the only subgenotype of HBV/A found in Cameroon. In Côte d'Ivoire, HBV/A strains were classified as HBV/A1 (11.1%), HBV/A2 (33.3%) and HBV/A3 (55.6%). Phylogeographic analysis of the sequences available from Africa supported earlier suggestions on the origin of HBV/A1, HBV/A2 and HBV/A3 in East, South and West/Central Africa, respectively. Using predicted amino acid sequences, hepatitis B surface antigen (HBsAg) was classified into serotype ayw4 in 93% of HBV/E strains and adw2 in 68% of HBV/A strains. Also, 7.7% of the sequences carried substitutions in HBsAg associated with immune escape.
  
  
  CONCLUSIONS
  The observations of pan-African and global dissemination of HBV/A1 and HBV/A2, and the circulation of HBV/E and HBV/A3 almost exclusively in West and Central Africa suggest a more recent increase in prevalence in Africa of HBV/E and HBV/A3 compared to HBV/A1 and HBV/A2. The broad genetic heterogeneity of HBsAg detected here may impact the efficacy of prevention and control efforts in sub-Saharan Africa.
authors.affiliation: Molecular Epidemiology and Bioinformatics Laboratory, Division of Viral Hepatitis, National Center for HIV, Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, 1600 Clifton Rd NE, Atlanta, GA 30333, USA. JForbi@cdc.gov
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Forbi
authors.forename: Yousr
authors.initials: Y
authors.lastname: Ben-Ayed
authors.forename: Guo-liang
authors.initials: GL
authors.lastname: Xia
authors.forename: Gilberto
authors.initials: G
authors.lastname: Vaughan
authors.forename: Jan
authors.initials: J
authors.lastname: Drobeniuc
authors.forename: William M
authors.initials: WM
authors.lastname: Switzer
authors.forename: Yury E
authors.initials: YE
authors.lastname: Khudyakov
mesh_terms: D017954:Africa South of the Sahara / Q000453:epidemiology; D016000:Cluster Analysis; D004279:DNA, Viral / Q000737:chemistry / Q000235:genetics; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006509:Hepatitis B / Q000453:epidemiology* / Q000821:virology*; D006514:Hepatitis B Surface Antigens / Q000235:genetics; D006515:Hepatitis B virus / Q000145:classification* / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D008297:Male; D017720:Molecular Epidemiology; D008969:Molecular Sequence Data; D058974:Phylogeography; D011247:Pregnancy; D015995:Prevalence; D017422:Sequence Analysis, DNA
chemical_list: D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens
keywords: Genotypes; Hepatitis B virus; Phylogenetic analysis; Sub-Saharan Africa; Subgenotypes