Tick-borne encephalitis virus (TBEV) infection has become a major health problem in Europe and is currently a common cause of viral brain infection in many countries. Encephalitis in transplant recipients, althrough rare, is becoming a recognized complication. Our study provides the first description of transmission of TBEV through transplantation of solid organs. Three patients who received solid organ transplants from a single donor (2 received kidney, and 1 received liver) developed encephalitis 17–49 days after transplantation and subsequently died. Blood and autopsy tissue samples were tested by next-generation sequencing (NGS) and reverse transcription polymerase chain reaction (RT-PCR). All 3 recipients were first analyzed in autopsy brain tissue samples and/or cerebrospinal fluid by NGS, which yielded 24–52 million sequences per sample and 9–988 matched TBEV sequences in each patient. The presence of TBEV was confirmed by RT-PCR in all recipients and in the donor, and direct sequencing of amplification products corroborated the presence of the same viral strain. We demonstrated transmission of TBEV by transplantation of solid organs. In such a setting, TBEV infection may be fatal, probably due to pharmacological immunosuppression. Organ donors should be screened for TBEV when coming from or visiting endemic areas.
Encephalitis is a severe neurological syndrome usually caused by viruses. Despite significant progress in diagnostic techniques, the causative agent remains unidentified in the majority of cases. The aim of the present study was to test an alternative approach for the detection of putative pathogens in encephalitis using next-generation sequencing (NGS). RNA was extracted from cerebrospinal fluid (CSF) from a 60-year-old male patient with encephalitis and subjected to isothermal linear nucleic acid amplification (Ribo-SPIA, NuGen) followed by next-generation sequencing using MiSeq (Illumina) system and metagenomics data analysis. The sequencing run yielded 1,578,856 reads overall and 2579 reads matched human herpesvirus I (HHV-1) genome; the presence of this pathogen in CSF was confirmed by specific PCR. In subsequent experiments we found that the DNAse I treatment, while lowering the background of host-derived sequences, lowered the number of detectable HHV-1 sequences by a factor of 4. Furthermore, we found that the routine extraction of total RNA by the Chomczynski method could be used for identification of both DNA and RNA pathogens in typical clinical settings, as it results in retention of a significant amount of DNA. In summary, it seems that NGS preceded by nucleic acid amplification could supplement currently used diagnostic methods in encephalitis.
Although hepatitis C virus (HCV) is primarily hepatotropic, markers of HCV replication were detected in peripheral blood mononuclear cells (PBMC) as well as in ex vivo collected tissues and organs. Specific strains of HCV were found to be capable to infect cells of the immune system: T and B cells and monocytes/macrophages as well as cell lines in vitro. The direct invasion of cells of the immune system by the virus may be responsible for extrahepatic consequences of HCV infection: cryoglobulinemia and non-Hodgkin’s lymphoma.
Encephalitis is a severe neurological syndrome associated with high morbidity and mortality as well as long-term neurological sequelae. Despite being an important public health problem, very few extensive population-based studies were conducted so far in the world and none in Central Europe. Altogether 114 consecutive patients meeting the initial criteria for encephalitis were enrolled at the Warsaw Hospital for Infectious Diseases between June 2012 and July 2015. Eighteen patients were secondarily excluded from the analysis due to incomplete data or noinfectious cause. Potential pathogen sequences were searched for by molecular methods in the cerebrospinal fluid (CSF) and specific antibodies were detected in CSF and sera. An infectious agent was identified in 41 patients (42.7%). The most frequently diagnosed infections were Human herpesvirus 1 (HHV-1) (22 cases, 24%) followed by Enterovirus (6 cases, 6.3%), Varicella zoster virus (VZV) (5 cases, 5.2%), Tick-borne encephalitis virus (TBEV) (6 cases, 6.3%) and Cytomegalovirus (CMV) (2 cases, 2.1%). There were no cases of human adenovirus, Human herpesvirus 6 (HHV-6) or West Nile virus (WNV) infection identified. In 55 cases (57.3%) the cause of encephalitis remained unknown. Compared to patients in whom the diagnosis was determined the latter group contained more women, was less likely to manifest fever and had lower CSF pleocytosis (p < 0.05) In summary, we identified HHV-1 followed by Enterovirus, VZV and TBEV as the most common causes of encephalitis among adult patients in Poland. In a large proportion of patients the cause of encephalitis remained unknown.
3 February 2022 in Archivum Immunologiae et Therapiae Experimentalis
Disturbances in gastrointestinal (GI) microbiota could play a significant role in the development of GI cancers, but the underlying mechanisms remain largely unclear. While some bacteria seem to facilitate carcinogenesis, others appear to be protective. So far only one bacterium (Helicobacter pylori) has been classified by the International Agency for Cancer Research as carcinogenic in humans but many other are the subject of intense research. Most studies on the role of microbiota in GI tract oncogenesis focus on pancreatic and colorectal cancers with the following three species: Helicobacter pylori, Escherichia coli, and Porphyromonas gingivalis as likely causative factors. This review summarizes the role of bacteria in GI tract oncogenesis.