Phylogenetic Analysis of Hepatitis B Virus Genotypes Circulating in Different Risk Groups of Panama, Evidence of the Introduction of Genotype A2 in the Country

Abstract

The Hepatitis B Virus (HBV) can cause acute or chronic infection it is also associated with the development of liver cancer, thousands of new infections occur on a yearly basis, and many of these cases are located in certain areas of the Caribbean and Latin America. In these areas, the HBV prevalence is still high which makes this virus a serious public health concern to the entire region. Studies performed in Panama suggest a complex pattern in the distribution of HBV among the country’s different risk groups. We use phylogenetic analysis in order to determine which HBV genotypes were circulating in these specific groups; for this we used a fragment of the PreS2/2 region of the HBV genome. Subsequently whole HBV genome sequences were used for Bayesian analysis of phylodynamics and phylogeography. Two main genotypes were found: genotype A (54.5%) and genotype F (45.5%). There was a difference in the distribution of genotypes according to risk groups: 72.9% of high risk groups were associated to genotype A, and 55.0% of samples of genotype F were associated to the low risk group (p<0.002). The Bayesian analysis of phylogeny-traits association revealed a statistically significant geographical association (p<0.0001) with both genotypes and different regions of the country. The Bayesian time of most recent common ancestor analysis (tMRCA) revealed a recent tMRCA for genotype A2 circulating in Panama (1997, 95% HPD: 1986—2005), when it is compared with Panamanian genotype F1c sequences (1930, 95% HPD: 1810 – 2005). These results suggest a possible change in the distribution of HBV genotypes in Panama and Latin America as a whole. They also serve to encourage the implementation of vaccination programs in high-risk groups, in order to prevent an increase in the number of new HBV cases in Latin America and worldwide.

Temporal and geographic spreading of hepatitis B virus genotype A (HBV‐A) in Brazil and the Americas

“…8 The phylogenetic analysis of HBV-A2 demonstrated clades of Eastern European origin that branch out to Southern Europe, North America, South America, Central America, Africa and Asia, reinforcing previous findings. 11,19 HBV-A2 seems to be disseminated from Eastern Europe to other continents and countries possibly spreading from Poland to Southern Europe, America and Asia between the 18th and 20th centuries.…”

“…10 It is the most frequently detected genotype (>50% in the population) in East and South Africa, Latin America and East Europe. 9,11,12 In Latin America, HBV-A is the main genotype in Brazil (58.7%), Cuba (92.5%), Haiti (71.0%) and Panama (54.6%). [11][12][13][14] Also, this genotype has a high whole-genome genetic diversity, being classified into seven different subgenotypes (A1 to A7).…”

“…9,11,12 In Latin America, HBV-A is the main genotype in Brazil (58.7%), Cuba (92.5%), Haiti (71.0%) and Panama (54.6%). [11][12][13][14] Also, this genotype has a high whole-genome genetic diversity, being classified into seven different subgenotypes (A1 to A7). Most of these subgenotypes are rare and restricted to very specific geographic regions, but HBV-A1 and HBV-A2 are more widespread and frequently detected in different countries.…”

“…8,9 Further, HBV-A1 and HBV-A2 are usually the only subgenotypes detected in most countries. 11,[13][14][15][16][17] HBV-A has a long evolutionary history with a common ancestor of more than one thousand years ago. 18 The two main subgenotypes (HBV-A1 and HBV-A2) seem to have emerged in two different continents: Africa and Europe.…”

Genetic Diversity of the Hepatitis B Virus Subgenotypes in Brazil

“…Latin America is the most plausible origin of HBV/F, where it circulates since the pre-Columbian times [49]. HBV/F subgenotypes are highly dispersed in South, Central America and in the native population of Alaska, being rarely found in other parts of the globe [33,50,51,52,53,54].…”