Acute Appendicitis Associated with Hantaan Virus Infection.

Hantaviruses are Bunyaviridae viruses that cause hemorrhagic fever with renal syndrome. Appendicitis caused by Hantaan virus has not been reported previously. An 81-year-old man who underwent laparoscopic appendectomy for suspected appendicitis based on abdominal pain, fever, hypotension, and computed tomography findings. Based on a suspicion of hemorrhagic fever with renal syndrome, the patient's plasma was simultaneously analyzed using an indirect immunofluorescent antibody assay and nested reverse transcription-polymerase chain reaction (RT-PCR). The appendix tissue was also analyzed using nested RT-PCR and immunohistochemical (IHC) staining to identify the presence of Hantaan virus. Nested RT-PCR detected the presence of Hantaan virus, and indirect immunofluorescent antibody assay results revealed the presence of elevated antibody levels. Furthermore, IHC staining of the appendix tissue confirmed Hantaan virus antigens in the peripheral nerve bundle. Based on these findings, we confirmed the nerve tropism of the Hantaan virus. Hantaan virus in plasma and appendix tissue samples was confirmed using PCR and phylogenetic tree analysis. Moreover, we detected hypertrophy of the submucosa and periappendiceal adipose tissue nerve bundle along with Hantaan virus antigens in peripheral nerve bundles using IHC staining. Hence, we report that Hantaan virus infection may be accompanied by appendicitis.

Sonographic distinction between acute suppurative appendicitis and viral appendiceal lymphoid hyperplasia ("pink appendix") with pathological correlation.

The viral etiology of mesenteric lymphadenitis may also affect the lymphoid tissue of the appendix in children giving rise to symptomatic appendiceal lymphoid hyperplasia, the so-called "pink appendix." The present study used ultrasound (US) to determine if certain sonographic features correlated with appendiceal pathological findings. Our results indicate that a fluid-filled appendix always correlates with a suppurative or mixed pathological appearance that likely merits surgery. A lymphoid predominant pathological appearance occurred only in cases where appendiceal wall thickening alone was seen on US. This pilot project therefore shows that US has the potential to stratify acute appendix patients into different treatment regimens, given that lymphoid hyperplasia could be treated conservatively. Further studies correlating other clinicoradiological parameters with this sonographic appearance are warranted.

Ovine herpesvirus 2 structural proteins in epithelial cells and M-cells of the appendix in rabbits with malignant catarrhal fever.

Sheep-associated malignant catarrhal fever (MCF), caused by Ovine herpesvirus 2 (OvHV-2), is a usually fatal disease of various ruminants and swine. A system for propagation of OvHV-2 in vitro has not yet been identified, although persistently infected cells have been derived from diseased animals and used to establish an animal model in rabbits. OvHV-2 structural proteins have not been detected in diseased animals and the pathogenesis of OvHV-2 infection is poorly understood. Recently, the genomic sequence of OvHV-2 has been determined, which allowed to predict the amino acid sequences of putative OvHV-2 structural proteins. Based on those predictions, we have generated antisera against two putative structural proteins (ORF43 and ORF63) of OvHV-2 in order to detect sites of active virus replication in experimentally OvHV-2-infected rabbits with signs of MCF. Although histological lesions typical of MCF were detected in multiple tissues, those sera detected viral capsid and tegument antigens exclusively in the appendix but not in other tissues of rabbits with MCF. More specifically, those viral proteins were detected in epithelial cells as well as in M-cells. However, in situ hybridization revealed that ORF63 mRNA was present in epithelial cells of infected rabbits but not in M-cells. Our data suggest that active OvHV-2 replication takes place in certain tissues of animals with MCF and that M-cells may play a role in the pathogenesis of MCF.

Variant Creutzfeldt-Jakob disease: prion protein genotype analysis of positive appendix tissue samples from a retrospective prevalence study.

OBJECTIVE: To perform prion protein gene (PRNP) codon 129 analysis in DNA extracted from appendix tissue samples that had tested positive for disease associated prion protein. DESIGN: Reanalysis of positive cases identified in a retrospective anonymised unlinked prevalence study of variant Creutzfeldt-Jakob disease (vCJD) in the United Kingdom. STUDY SAMPLES: Three positive appendix tissue samples out of 12,674 samples of appendix and tonsil tested for disease associated prion protein. The patients from whom these samples were obtained were aged 20-29 years at the time of surgery, which took place in 1996-9. SETTING: Pathology departments in two tertiary centres in England and Scotland. RESULTS: Adequate DNA was available for analysis in two of the three specimens, both of which were homozygous for valine at codon 129 in the PRNP. CONCLUSIONS: This is the first indication that the valine homozygous subgroup at codon 129 in the PRNP is susceptible to vCJD infection. All tested clinical cases of vCJD have so far occurred in the methionine homozygous subgroup, and a single case of probable iatrogenic vCJD infection has been identified in one patient who was a methionine/valine heterozygote at this genetic locus. People infected with vCJD with a valine homozygous codon 129 PRNP genotype may have a prolonged incubation period, during which horizontal spread of the infection could occur either from blood donations or from contaminated surgical instruments used on these individuals during the asymptomatic phase of the illness.

Detection of HGV RNA in digestive organs.

The organ where the GB virus (GBV)-C/hepatitis G virus (HGV) localizes and proliferates is not known. We examined the digestive organs for HGV RNA to determine the localization of the HGV. Two cases of patients with serum-positive HGV RNA were investigated. We embedded surgically excised materials and digestive secretion materials from cases 1 and 2 in paraffin blocks. The tissue specimens investigated included lymph nodes No. 201 and 202, ascending colon (nontumor and tumor area), ileocecum, appendix, liver (nontumor and tumor area) and gall bladder. We made cDNA after extraction of total RNA from thin tissue sections and detected HGV RNA with a reverse transcription polymerase chain reaction method. No HGV RNA was detected in liver, colon and gall bladder tissues. HGV RNA was only detected in the appendix tissue. Comparison of nucleotide sequences of PCR products from serum and appendix was almost the same. Homology between US type (PNF2161) and the serum and appendix PCR products was 92.6 and 93.6%, respectively. These results suggest that HGV proliferates in the appendix and is carried by the portal blood flow to the liver, and may cause a hepatitis reaction in the liver.

Immunizing effect of vaccinia virus expressing the nucleoprotein of rinderpest virus on systemic rinderpest virus infection in rabbits.

A recombinant vaccinia virus (RVV) expressing the nucleoprotein (NP) of rinderpest virus (RPV) was examined in rabbits for the involvement of the NP protein in protection from the RPV infection. Despite their production of anti-NP antibody, the RVV-immunized rabbits succumbed to the RPV challenge, although there was a slight delay in the onset of disease after the low-dose challenge. On the other hand, the animals immunized with RVV expressing the hemagglutinin (H) protein of the RPV were completely protected. These results indicate that the NP protein might be not so effective as the H protein for the protection against viremic and systemic infection with RPV.

Down-regulation of CD95 (Fas/Apo-1) in the epithelia of adenovirus-infected appendices.

AIMS: Adenoviral inclusions are commonly seen in appendices from infants with intussusception. They are associated with focal epithelial budding and less frequently with epithelial shedding. These morphological changes could depend on the opposing effects of adenoviral gene products on CD95-mediated apoptosis. METHODS AND RESULTS: Appendices from intussusceptions with viral inclusions (n = 4) and normal appendices (n = 10) were studied by immunochemistry with anti-adenovirus, anti-CD95 and anti-HLA-DR antibodies. Apoptosis was studied by the TUNEL method. The mucosa of normal appendices contained no adenoviral protein. CD95 was present in all epithelial cells except Paneth cells. HLA-DR was absent in epithelial cells and apoptosis was seen only in germinal centres and in a few surface epithelial cells. The epithelium of appendices from intussusceptions contained nuclear inclusions labelled with anti-adenovirus antibody, always found in the epithelial buds. The epithelial CD95 pattern was drastically altered in adenovirus-infected appendices. CD95 was absent from the budding foci. In these foci, HLA-DR was overexpressed. There was also increased epithelial apoptosis in areas remote from those lacking CD95 antigen. CONCLUSIONS: The appearance of epithelial budding or shedding in appendices from intussusception could be due to focal in situ differences in the expression of adenoviral genes.

[Adenovirus and intranuclear inclusions in the appendix in children with acute intussusception]. / Adénovirus et inclusions intranucléaires dans les appendices au cours des invaginations intestinales aiguës de l'enfant.

One hundred and five appendices removed at the time of surgical reduction of intussusception in children were studied by light microscopy after routine procedures to search for aetiological factors involved in intussusception. Normal pediatric appendix specimens served as controls (n = 30). Light microscopic examination showed viral inclusions in epithelial cells in 48 of 105 appendices (45%) from the cases of intussusception. No viral inclusion was observed in controls. Immunohistochemistry performed on 21 appendices from intussusception with a monoclonal antibody against adenovirus showed intranuclear positivity in all appendices with viral inclusions. Viral inclusions seen in epithelial cells of appendices from cases of intussusception are caused by virus and in particularly by adenovirus. The etiological factors involved in intussusception without viral inclusion in appendix remain unknown.