Genotypes of hepatitis a virus in Turkey: first report and clinical profile of children infected with sub-genotypes IA and IIIA

Abstract

BackgroundHepatitis A virus (HAV) is a food and water-borne virus causing clinical (mainly hepatitis) and subclinical disease in humans. It is important to characterize circulating strains of HAV in order to prevent HAV infections using efficacious vaccines. The aim of this study was the detection and characterization of the circulating strains of HAV in Turkey by performing serology, RT-PCR, sequencing and phylogenetic analysis.MethodsIn this study, 355 HAV suspected cases were analysed by ELISA for the presence of antibodies to HAV. RNA was extracted from 54 HAV IgM positive human sera. None of the suspect cases were vaccinated against HAV and they never received blood transfusions. Samples found positive by RT-PCR using primers targeting the VP1/VP2A junction and VP1/VP3 capsid region of HAV, were subjected to sequencing and phylogenetic analyses.ResultsIgM type antibodies to HAV were detected in 54 patients. Twenty one of them were students. The age of IgM positive cases was between 3 and 60 years. IgM positivity differed in age groups and was higher in the age group 3 to 10 years. Phylogenetic analysis showed that the majority of HAV strains detected in this study belong to the “HAV 1B” cluster. In addition, the HAV sub-genotypes IA (KT874461.1) and IIIA (KT222963.1) were found in 2 children. These sub-genotypes were not previously reported in Turkey. The child who carried sub-genotype IIIA travelled to Afghanistan and presented with abdominal pain, icterus and vomitus. He was positive for anti-HAV IgM and IgG but negative for hepatitis B and C. Liver enzymes like aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, gamma-glutamyl transferase and lactate dehydrogenase were severely elevated. Bilirubin levels were also increased. White blood cells, neutrophils and hemoglobin were decreased while lymphocytes and monocytes were increased. Similar clinical signs and laboratory findings were reported for the child infected with sub-genotype IA but aspartate aminotransferase and alanine aminotransferase were not severely elevated.ConclusionsThe results indicate that molecular studies determining the HAV genotype variation in Turkey are timely and warranted. The majority of IgM positive cases in 3–10 year old patients indicate that childhood vaccination is important. Sub-genotype IB is the most prevalant genotype in Turkey. Surprisingly, sub-genotype IA and IIIA are also present in Turkey; future diagnostic efforts need to include diagnostic methods which can identify this emerging HAV genotypes. Our results also show that one important risk factor for contracting hepatitis A virus is international travel since genotype IIIA was detected in a child who had travelled to Afghanistan.

Biochemical Features of an Acute Viral Hepatitis A Outbreak

“…In Bulgaria, during a period of 3 years (2012-2014), almost in the same period with our Romanian South Eastern outbreak, subtype IA was found as dominant (74%) versus subtype IB (26%) [20]. In a study performed by Yilmaz in children from Turkey, the predominant subtype was IB and, in addition, two children were diagnosed with subtype IA and IIIA and the child with HAV subtype IIIA travelled from Turkey to Afghanistan and had a severe evolution [21]. Although many studies suggest that subtype IA of HAV is predominant in Europe, further studies in order to evidence the exactly subtype of HAV circulating in Romania are required [19,20].…”

Insights into Gastrointestinal Virome: Etiology and Public Exposure

“…Despite the high conservation of HAV, a degree of genomic sequence divergence exists defining the various HAV genotypes and the identity of sub-genogroups [192,193]. Consequently, HAV genotyping is dependent on different regions of its genome used to recognize HAV variants, including the VP1 entire region, notably the VP1 amino terminus, the 168 bp VP1-2A junction, the VP1-2B region, the VP3-2B region, the VP3 carboxy-terminus, and the 5 untranslated region [194,195]. Based on VP1-2A junction region variability (of ~15%), seven genotypes of HAV were primarily defined.…”

Hepatitis A Virus Genotype IB Outbreak among Internally Displaced Persons, Syria

“…We performed collections during May-August by flagging vegetation or using CO 2 traps (5). We completed identification by using established keys (6).…”