RESUMEN
Hepatitis A virus isolates from anti-HAV IgM positive sera of 70 hepatitis cases in two outbreaks and 216 other cases in Central America, 136 sporadic cases and 53 cases from an hyper-endemic region in Costa Rica, were compared by phylogenetic analyses within the VP1 region. The outbreaks in all 531 cases, in 1992 and 1999, respectively, were presumed water borne. In the first outbreak, HAV RNA could be detected in 70% of the cases sampled during 6 weeks after onset of jaundice. In the hyper-endemic region of San Ramón in Costa Rica, 1,932 cases were registered between 1972 and 1985. All isolates belonged to subtype 1A. Background isolates from Costa Rica and El Salvador tended to form separate subclusters in the phylogenetic tree construction and were mostly unrelated to subtype 1A strains from other parts of the world. Based on their amino acid sequences, four HAV strains, all related to CR326 sampled in Costa Rica in 1960, were found to have circulated in the area during the last three decades. However, on the basis of nucleotide variability the isolates from the outbreaks could be distinguished from the strains from sporadic cases and sequence analysis could confirm the epidemiological homogeneity of both outbreaks. In the hyper-endemic region, 16 different sequences were encountered forming one single subcluster. Thus, limited sequencing within the VP1 region proved useful to identify outbreaks of hepatitis A in a highly endemic area, where most strains were local and only one subtype was prevalent.
Asunto(s)
Brotes de Enfermedades , Enfermedades Endémicas , Virus de la Hepatitis A/clasificación , Virus de la Hepatitis A/genética , Hepatitis A/epidemiología , Adolescente , Adulto , Niño , Preescolar , Costa Rica/epidemiología , El Salvador/epidemiología , Genotipo , Hepatitis A/virología , Anticuerpos de Hepatitis A , Virus de la Hepatitis A/aislamiento & purificación , Anticuerpos Antihepatitis/sangre , Humanos , Epidemiología Molecular , Datos de Secuencia Molecular , Filogenia , Reacción en Cadena de la Polimerasa , Análisis de Secuencia de ADN , Proteínas Estructurales Virales/genéticaRESUMEN
The S genes of 31 Central American hepatitis B virus (HBV) strains belonging to genotypes A, C, D, and F (4, 1, 4, and 22 strains, respectively) were compared with 104 published S genes. According to the deduced S gene product, 21 genotype F strains encoded adw4, while 1 encoded ayw4. Three clusters were revealed within genotype F, which correlated with substitutions at residue 45. In a cluster of 18 Central American and 1 Alaskan strain, all had Thr45. One cluster included 2 Central American strains and 6 strains from South America and Europe, which had Leu45. Two Nicaraguan strains differed by five substitutions, including a Pro45 in the S gene product from other F strains. In conclusion, the dominating HBV genotype was F, which might be the reason for a low prevalence of HBV in the area, despite high prevalence of hepatitis A. These infections otherwise vary in parallel and are considered to reflect socioeconomic conditions.
Asunto(s)
Antígenos de Superficie de la Hepatitis B/genética , Virus de la Hepatitis B/clasificación , Hepatitis B/epidemiología , Hepatitis B/genética , Epidemiología Molecular , Secuencia de Aminoácidos , América Central/epidemiología , ADN Viral/análisis , ADN Viral/genética , Genes Virales , Anticuerpos contra la Hepatitis B/análisis , Anticuerpos contra la Hepatitis B/inmunología , Antígenos de la Hepatitis B/análisis , Antígenos de la Hepatitis B/genética , Antígenos de Superficie de la Hepatitis B/inmunología , Antígenos e de la Hepatitis B/inmunología , Virus de la Hepatitis B/genética , Virus de la Hepatitis B/inmunología , Humanos , Leucina/genética , Datos de Secuencia Molecular , Filogenia , Mutación Puntual , Reacción en Cadena de la Polimerasa , Prolina/genética , Alineación de Secuencia , Análisis de Secuencia de ADN , Homología de Secuencia de Aminoácido , Treonina/genéticaRESUMEN
The distribution of HBV genotypes and the presence of the precore stop mutation were investigated in HBV strains from Central America. 333 HBsAg positive sera from chronic HBsAg carriers and acute hepatitis B cases from five different countries (Costa Rica, Nicaragua, Honduras, EI Salvador and Guatemala) were tested for HBV DNA by nested PCR. Genotyping by limited sequencing within the S gene was performed on 90 strains, 66 from sera with a high level of HBV DNA, and another 24 from sera positive for HBV DNA only after nested PCR. 23 of the samples were anti-HBe positive. Genotype F was found in 71 (79%), A in 13 (14%), D in 5 (6%) and C in one of the 90 sera. 18 patients with genotype F infection had anti-HBe and HBV DNA in serum. Since the three published precore sequences of genotype F strains have a C1858, which is known to prevent the precore stop mutation from G to A at position 1896, the precore and part of the core genes were sequenced from 19 anti-HBe positive sera with HBV DNA, 17 with genotype F and 2 with genotype A. The A1896 mutation was found in 11 of the 17 genotype F strains. All these had a T1858, which was also present in 5 of the 6 genotype F strains with G1896. The precore region was therefore sequenced from genotype F strains from 5 HBeAg positive sera from the five different Central American countries. These also had a T1858, which thus is the wild type substitution in genotype F in Central America. A number of mutations were recorded between residues 57 and 68 in the core protein corresponding to a unique clustering region of the genotype F strains. The predominance of genotype F in Central American populations of Hispanic origin was not anticipated since this genotype is regarded as indigenous to the Amerindian populations of the New World.