Hepatitis A virus subtype IB outbreak among MSM in Hungary with a link to a frozen berry source.

Men who have sex with men (MSM) are at high risk of acquiring hepatitis A virus (HAV) and in recent years several HAV outbreaks mostly affecting MSM have been described. These outbreaks were caused by subtype IA strains circulating in this high-risk population. After years of low incidence, an outbreak among MSM in Hungary caused a significant increase in reported HAV infections in 2022. Samples from 224 HAV IgM-positive patients diagnosed in 2022 were tested for HAV RNA and positive samples were genotyped by sequencing. In 171 patients a unique subtype IB virus was detected with 99.8-100% sequence identity in the VP1/P2A junction. It was distinct from previously published strains, but most closely related to an Egyptian isolate. Sequence analysis revealed one dominant and three minor variants based on VP1/P2A. Whole genome sequencing revealed limited variation among these variants, suggesting a recent common origin. Epidemiological data indicated that sexual transmission was driving the outbreak for most of the year, suggested by the high male to female ratio and the large number of coinfections with HIV and other sexually transmitted infections among the patients. The outbreak was also associated with a restaurant cluster, in which one of the variants was detected and frozen berries were implicated as the source of infections. The outbreak strain was also detected in other countries around Europe and remained frequently detectable in Hungary in 2023. This study provides insights into the molecular and epidemiological characteristics of the described HAV outbreak. The results show that sequencing is not only useful in connecting cases to an outbreak, but also helps to clarify the relatedness of detected variants. Prevention strategies focusing on vulnerable communities may reduce the burden of HAV infections in the future.

Prevalence and genotypes of human papillomavirus in saliva and tumor samples of head and neck cancer patients in Hungary.

In addition to traditional risk factors such as smoking, alcohol consumption and betel nut use, human papillomavirus (HPV) infection also plays a role in the development of head and neck squamous cell carcinomas (HNSCCs). Although among European countries the highest incidence and mortality rates of head and neck cancer types were recorded in Hungary, data regarding HPV prevalence in HNSCCs is scarce. We collected biopsy and saliva samples from patients diagnosed with HNSCC or oral potentially malignant disorders (OPMDs) and tested them for the presence of HPV using the PCR consensus primer set MY09/11 and the GP5+/6+ primer pair. HPV genotypes were assessed by sequencing of the amplified PCR fragments. Oral mucosa and saliva samples from tumor- and OPMD-free individuals were also analysed. HPV was detected in 11 out of 60 HNSCC samples (18%). All of the HPV positive tumors carried HPV type 16. 5 out of the 57 saliva samples collected from HNSCC patients was HPV positive (8.8%); among them, in addition to HPV16, HPV13 was also detected. Tumors located to the oropharynx had the highest HPV positivity rate with 50% (7 out of 14), which was significantly higher than the HPV prevalence in oral mucosa samples collected from controls (0 out of 20; p > 0.001) or in OPMD biopsies (0 out of 21, p > 0.001). 2 out of 57 control saliva samples (3.5%, subtype HPV13 and 11) and 3 out of 39 saliva samples from OPMD patients (7.7%, subtype HPV18, 81 and 10) were HPV positive. Our data suggested that HPV16 infection may contribute, in concert with cigarette smoking, to the development of a subset of head and neck cancers in Hungary. HPV16 infection per se does not account, however, for the high HNSCC incidence rate recorded in this country.

Phylogenetic analysis of a transfusion-transmitted hepatitis A outbreak.

A transfusion-associated hepatitis A outbreak was found in the first time in Hungary. The outbreak involved five cases. Parenteral transmission of hepatitis A is rare, but may occur during viraemia. Direct sequencing of nested PCR products was performed, and all the examined samples were identical in the VP1/2A region of the hepatitis A virus genome. HAV sequences found in recent years were compared and phylogenetic analysis showed that the strain which caused these cases is the same as that had spread in Hungary recently causing several hepatitis A outbreaks throughout the country.

Detection and Phylogenetic Analysis of Torque Teno Virus in Salivary and Tumor Biopsy Samples from Head and Neck Carcinoma Patients.

OBJECTIVES: Because torque teno virus (TTV) has been implicated in tumorigenesis as a cocarcinogen, we studied TTV prevalence in saliva and biopsy samples from head and neck cancer (HNCC) patients, patients with premalignant lesions of oral cancer, and controls. We also wished to determine the TTV genotypes in HNCC patients. METHODS: A seminested polymerase chain reaction (PCR) amplifying the N22 region of the TTV genome, as well as direct sequencing of PCR fragments, was used. RESULTS: TTV prevalence was higher in HNCC patients (saliva: 27/71, 38%; tumor biopsy: 22/74, 30%) than in controls (saliva: 8/56, 14%; oral mucosa: 1/19, 5%). TTV prevalence was also high in patients with premalignant lesions of oral carcinoma (saliva: 9/18, 50%; biopsy: 5/21, 24%). By phylogenetic analysis, TTV belonging mostly to genotypes 1 and 2 was found in HNCC patients. In most of the cases, identical TTV strains were present in the biopsy and salivary sample of the same HNCC patient. In addition, the same TTV strain was detected in 2 laryngeal carcinoma biopsies obtained from 2 independent patients. CONCLUSIONS: Our data are compatible with the idea that TTV might act as a cocarcinogen in certain cases of HNCC. Alternatively, HNCC may facilitate either TTV replication or TTV entry into the saliva.

An archived serum sample as a clue for identifying the primary source of a nosocomial hepatitis C virus outbreak in a haemodialysis unit.

Due to an unexpected technical error, patients at a dialysis unit who were seronegative for hepatitis C virus (HCV) were temporarily transferred to another dialysis unit next to a ward reserved for HCV-seropositive patients. In the following 7 months, 17 patients were diagnosed as anti-HCV positive. The aim of the study was to reveal the cause of this nosocomial infection. Anti-HCV-positive sera were further tested by molecular methods. Data collection and on-site epidemiologic inspections were carried out. The source of the nosocomial infection proved to be a seropositive patient treated at the unit, who died before the outbreak was recognized. The exact date of the infection was determined.

Prevalence and correlates of HCV, HVB, and HIV infection among prison inmates and staff, Hungary.

The aim of this national, multicenter, cross-sectional study was to assess the prevalence of hepatitis B (HBV), hepatitis C (HCV), and human immunodeficiency viruses (HIV) among prisoners, and to identify related risk behaviors including injection drug use. Overall, 4,894 inmates from 20 prisons were enrolled. To have a comparison group, prison staff were also asked to take part. Altogether, 1,553 of the 4,894 inmates from seven prisons completed a questionnaire on risk behaviors. According to the survey, 1.5%, 4.9%, and 0.04% of the prisoners were tested positive for HBsAg, anti-HCV and anti-HIV, respectively. These prevalence data are among the lowest reported from prisons worldwide, although comparable to the Central European data. The prevalence of HBV, HCV, and HIV in the Hungarian prison staff was low (0.38%, 0.47%, and 0%, respectively). The rate of HCV infection was significantly higher among inmates who have ever injected drugs (22.5%) than among inmates who reported they had never injected drugs (1.1%). This first prevalence study of illegal drug injection-related viral infections among Hungarian prisoners points out that ever injecting drugs is the main reason for HCV infection among inmates. The opportunity to reach drug users infected with HCV for treatment underlines the importance of screening programs for blood-borne viruses in prisons.

Phylogenetic analysis of a nosocomial transmission of hepatitis B virus at a paediatric haematology ward.

A nosocomial Hepatitis B virus (HBV) outbreak at a paediatric onco-haematology unit was investigated using molecular biological methods to determine the origin of the infections. The National Reference Laboratory of Hepatitis Viruses received seven HBsAg positive sera from patients and one from the brother of a patient. A fragment of the preS1/preS2/S genes from all samples was amplified, the PCR products were sequenced and a rooted phylogenetic tree was constructed. All nucleotide sequences from the different patients were very similar and 6 of the 8 sequences were identical, suggesting a common origin of the infections. These sequences were closely related to those amplified from a nosocomial HBV epidemic in another hospital in Hungary. The on-scene investigation revealed several malpractices. The two hospital departments had close connections and some of the patients were treated in both institutions. Present report underlines the importance of developing screening protocols for hepatitis viruses and that of the introduction of regular training programs for health care professionals in the field of hospital hygiene.

Phylogenetic investigation of nosocomial transmission of hepatitis C virus in an oncology ward.

Nosocomial hepatitis C virus (HCV) infections have been reported from different health-care settings worldwide. Twenty patients, treated at the same oncology department, with no previous record of hepatitis C infection, tested positive for anti-HCV antibodies between November 2007 and June 2008. Twelve of the newly infected patients were found to be HCV RNA positive. The common origin of the infections was assumed. To investigate the relatedness of the detected viral strains phylogenetic analyses were performed using sequences from the NS5B and E1/E2 genome regions. A patient carrying HCV for years was also involved in the study. She was treated at the same oncology department and was considered a possible infectious source. The previous HCV carrier harbored subtype 1b, while all other patients were infected with subtype 1a. Sequences from the 12 newly infected patients formed two groups. The viral sequences within the groups were very closely related. A greater evolutionary distance was observed between the two groups; however, their relatedness could be demonstrated by sequences from both regions with high statistical support. The results indicated that nosocomial transmission occurred. The phylogenetic analyses suggested that the viruses originated from a common source, possibly a patient carrying highly divergent variants. This presumed infectious source could not be identified in the course of this study. The genotype distribution of Hungarian control sequences included in the analysis confirmed this conclusion, since HCV genotype 1a was found to be relatively uncommon.

Mutation spectra of the surface-protein-coding region of the HBV genome in HBV-vaccinated and non-vaccinated individuals in Hungary.

Hepatitis B virus (HBV) infection has a major effect on health care systems, with about one-third of the world's population currently infected with the virus. There is an effective vaccine against HBV, which contains a recombinant "surface antigen" produced in an expression vector. Vaccination has proved to be successful in Hungary: the number of acute HBV cases has decreased in the past 10 years. Although an increasing number of publications report on "vaccine-escape" HBV variants which can infect HBV-vaccinated individuals, such mutant HBV strains have not yet been detected in Hungary. We therefore surveyed two risk groups for vaccine-escape or immunoglobulin-escape HBV mutations in Hungary: 28 actively and/or passively HBV-immunized children of HBV carrier mothers who proved to be HBsAg and/or anti-HBc positive and 40 symptomless HBV carrier pregnant women (presumably carrying genotype B or C). We focused on the coding sequences of the "a" immundominant region of the surface protein. We could not detect the G145R amino acid substitution associated with vaccine escape mutant virus. However, we could map other mutations potentially affecting the immunodominant "a" region of the HBV surface protein.

First description of swine Torque teno virus (TTV) and detection of a new genogroup in Hungary: short communication.

Torque teno virus (TTV) belongs to the floating genus of Anellovirus. It was discovered in a human patient, and later it was also found in animals including pigs. The aim of this study was to investigate the presence and estimate the prevalence of swine TTV in Hungarian pig herds for the first time, and to characterise the viruses found. Serum samples of 82 adult swine from 13 piggeries and 44 weaned pigs from one large herd were tested by PCR for the presence of TTV DNA. Viral DNA was found in 30% of the adult swine and 73% of the weaned pigs tested. Liver and intestine of weaned pigs were also tested and found to be infected at a lower rate. The TTV sequences found in sera and intestines were similar and could be clustered as swine genogroup 1. However, the sequences derived from one liver were remarkably different from all other known genogroups and seemed to represent a new genogroup.

Prevalence and genotypes of hepatitis G virus/GB virus C in a multirisk group in Hungary.

HGV/GBV-C is a mainly parenterally transmitted Flavivirus that causes a persistent infection. So far no disease has been associated with HGV/GBV-C infection, but its beneficial role in co-infection with the human immunodeficiency virus has been shown in many recent studies. The aim of our study was to determine the frequency of ongoing HGV/GBV-C infections among a sociologically unique group of the Hungarian population, who are at great risk for parenterally transmitted diseases. Viral RNA was detected in 75 serum samples by an RT-PCR method specific for the NS5 region. Nine (12%) samples were positive for HGV/GBV-C RNA. All nine PCR products were sequenced and a phylogenetic analysis was performed to identify the genotypes and subtypes of the detected viruses. All nine isolates proved to be genotype 2, eight of them were classified as subtype 2a, and one as subtype 2b.

[Newly discovered hepatitis viruses--do they cause hepatitis indeed?]. / Ujonnan felfedezett hepatitisvírusok: de okoznak-e májgyulladást?

The paper reviews the available information on the newly discovered viruses originally supposed to cause post-transfusion hepatitis. GBV-C/Hepatitis G virus belongs to the Flaviviridae family, and can be transmitted parenterally like Hepatitis C virus. Its role in causing hepatitis or other diseases has not been proved yet. The other newly discovered viruses contain single-stranded circular DNA, with a wide range of sequence divergence. These viruses can be transmitted not only with blood and blood products but via fecal-oral route as well. They are unique among enterally transmitted viruses in the sense that the virus persists for years in the human body, therefore their genomes may be detected in the blood of the healthy population in high percentage. One of the genotypes of TTV is suspected to cause hepatitis. High TT virus load was found as an independent factor associated with the occurrence of hepatocellular carcinoma among patients with hepatitis C virus-related chronic liver disease. It is not clear yet, whether TTV-like minivirus and SEN virus cause any illnesses.

Prevalence of GB virus C/hepatitis G virus in Hungary.

In 1995 a new flavivirus, GB virus C/hepatitis G virus (GBV-C/HGV), was discovered. The aim of this study was to determine the prevalence of the virus in healthy persons and hepatitis patients in Hungary. The sera of 408 healthy persons older than 60 years were tested for the presence of GBV-C/HGV antibodies, and 113 were positive (28%). Eight of the 71 healthy persons younger than 60 years and twenty of the 51 sera (39%) taken from patients suffering from hepatitis of unknown origin proved to be positive for GBV-C/HGV antibodies. Ten of the 124 sera (8%) of healthy persons and 36 of the 247 sera (14.6%) of hepatitis patients proved to be positive for GBV-C/HGV RNA. Eleven PCR products were sequenced, and the sequences were found to be different from each other and from the previously published ones. However, three sequences taken from the same patient at different times were identical. These results show that GBV-C/HGV is present in Hungary and cannot be considered rare.