[Molecular detection and sequence analysis of hepatitis A virus (HAV) in two outbreaks in 2004 in North East Hungary]. / Hepatitis A-vírusok molekuláris biológiai kimutatása es elemzése két 2004 evi eszakkelet-magyarországi járványból.

INTRODUCTION: Hepatitis A virus (HAV) is the most important cause of acute infectious hepatitis worldwide. In Hungary, the reported number of HAV infections decreasing in the last decades, however, in every year approximately 500-800 new cases occur. In Hungary, particularly in North East region not only sporadic cases but also outbreaks of HAV are happen from time to time. Serology is routinely used laboratory method for diagnosis of HAV infections, although, there was no direct molecular detection and sequence analysis for the circulating HAV strains in Hungary. AIMS: Author's aims were to detection and genetic characterization of hepatitis A virus in outbreaks of hepatitis by molecular methods for reason of molecular epidemiology in Hungary. MATERIALS AND METHODS: Sera samples from symptomatic patients were tested from two acute hepatitis outbreaks in two settlements (Hajdúböszörmény and Kázsmárk) in North East Hungary in 2004 by enzim-immunoassay (EIA) and reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Sera in 58 (100%) and 4 (28.6%) symptomatic patients were positive in outbreaks of Hajdúböszörmény and Kázsmárk by HAV IgM EIA, however, 4 (57.1%) and 2 (66.6%) HAV IgM positive samples were positive by RT-PCR. By sequence analysis, outbreaks caused by the same hepatitis A virus which belongs to genotype I, subtype IA. These viruses had 98.4% nucleotide identity to IT-SCH-00 virus detected in year 2000 in Italy the closest match in GenBank. CONCLUSIONS: Methods of molecular biology give new opportunity for surveillance of infectious diseases in public health. Firstly characterized hepatitis A viruses in Hungary show that the subtype IA have an important epidemiological role in outbreaks. It is also suggested that genotype IA HAV play a part in sporadic HAV cases in endemic region in Hungary, too.

Gluten intake interferes with the humoral immune response to recombinant hepatitis B vaccine in patients with celiac disease.

OBJECTIVE: Patients with celiac disease, who often carry human leukocyte antigen-DR3;DQ2, are prone to inadequate response to hepatitis B immunization. We evaluated vaccine response in relation to disease activity and whether previous treatment with a gluten-free diet influences the achievement of protective antibody titers. PATIENTS AND METHODS: We studied 128 children and adolescents with celiac disease and 113 age-matched control subjects. Twenty-two patients with celiac disease were prospectively immunized after diagnosis during dietary treatment (group 1). A total of 106 (group 2) and the control subjects received vaccination by mass immunization in schools at 14 years of age regardless of diet status and when celiac disease was still undiagnosed in 27 of these children. Diet compliance and celiac disease activity were monitored by measurement of antibodies against transglutaminase and endomysium. Vaccine response was determined by measuring antihepatitis B antibodies from serum. RESULTS: The seroconversion after hepatitis B vaccination was 95.5% in group 1. All of these patients carried human leukocyte antigen DQ2. The response rate in group 2 was 50.9% and correlated with gluten intake (untreated patients: 25.9%, non-strict diet: 44.4%, strict diet: 61.4%). Treated and compliant patients did not significantly differ from control subjects (75.2%). Thirty-seven antihepatitis B-negative patients with celiac disease received a booster during a controlled gluten-free diet, and 36 (97.3%) seroconverted, irrespective of the presence of human leukocyte antigen DQ2. CONCLUSIONS: Nonresponse to recombinant hepatitis B surface antigen may be a sign of undiagnosed celiac disease. However, there is a good vaccine response in adequately treated patients. Human leukocyte antigen DQ alleles do not seem to have a primary role. Revaccination is recommended during a controlled gluten-free diet.

Co-circulation of genotype IA and new variant IB hepatitis A virus in outbreaks of acute hepatitis in Hungary--2003/2004.

Hepatitis A virus (HAV) is one of the most important causes of acute infectious hepatitis worldwide. In Hungary, the reported number of HAV infections has been decreasing in the last four decades, nevertheless, still, each year 500-800 new cases and multiple outbreaks occur, particularly in the northeast region of Hungary. In Hungary, serology is used routinely to establish the diagnosis of HAV infection without genetic analysis of HAV strains for molecular epidemiology. In this study, serum samples collected from symptomatic patients were tested by enzyme-immunoassay (anti-HAV-IgM ELISA) to establish the cause of three acute hepatitis A outbreaks (outbreak 1--from low prevalence region in Southwest Hungary in 2003 and outbreaks 2 and 3 from the endemic region in Northeast Hungary in 2004). Outbreak strains were characterized by reverse transcription-polymerase chain reaction (RT-PCR) amplification of a 360 bp viral VP1/2A region, amplicon sequencing and phylogenetic analysis. Four, seven, and three sera from outbreaks 1, 2, and 3, respectively, were investigated by RT-PCR for HAV genome and HAV RNA was detected in 4 (100%), 4 (57%), and 2 (67%) samples. All strains belonged to genotype I HAV. Outbreak 1 was caused by the new variant subtype IB and outbreaks 2 and 3 caused by genetically identical subtype IA strains. The Hungarian IA and IB hepatitis A viruses had the highest nucleotide identity, 98.4% and 99.0%, to IT-SCH-00 and IT-MAR-02 strains, respectively, detected in year 2000 and 2002 in Italy. Endemic subtype IA and probably imported new variant subtype IB HAV viruses was detected in outbreaks of hepatitis in Hungary that are closely related genetically to HAV strains in Italy.