Adaptation of Trichinella nativa in hosts

Trichinella nativa is a member of the genus Trichinella, which includes nine different species and three genotypes. Trichinella spp. are spread worldwide and they can cause a disease called trichinellosis in both animals and humans. In this thesis, the epidemiology of T. nativa and other Trichinella species in a boreal environment was investigated. Unusual T. nativa infection in a domestic cat with clinical signs was reported. Host responses induced by T. nativa and Trichinella spiralis were compared in a selective host (rat) to identify the phase of the life cycle in which the selective responses take place. Of the 2483 carnivorous samples collected from Finland, 617 (24.8%) were positive for Trichinella spp. with higher prevalence in the North compared to southern part of the country. Four endemic Trichinella species were identified using multiplex PCR: T. spiralis, T. nativa, Trichinella britovi, and Trichinella pseudospiralis. Trichinella nativa was shown to be the predominant Trichinella species (80.1%) in all investigated wild host species. Red fox and raccoon dog were the most important reservoir animals when population size, estimated prevalence of Trichinella infection, and infection intensity were taken into account. Trichinella infection can cause clinical manifestations; a domestic cat had an ulcer below the eyelid and a skin biopsy revealed one Trichinella sp. larva surrounded by inflammatory reaction and granulation tissue. Enzyme-linked immunosorbent assay and Western blotting showed a seropositive reaction against Trichinella spp. antigens in the cat s serum. The Trichinella sp. larva was identified as T. nativa by multiplex PCR. During the 1-year follow-up, a subcutaneous mass started to cover the previous surgical site. A biopsy sample taken from that area showed inflammatory cells and fibroblasts, with some fibrodysplasia. To identify the phase of the life cycle in which the defense against Trichinella takes place, rats were infected both per orally (p.o.) and intravenously (i.v.) with T. nativa and T. spiralis larvae. After i.v. injection, 1.7% of the T. nativa NBL and 20% of the T. spiralis NBL reached the muscle tissue of the rat (p less than 0.05). These results showed that the defense against Trichinella did not solely localize to the enteral or parenteral phase. The different infectivity of the two Trichinella species can also be partly explained by difference in reproductivity; T. nativa females isolated from a mouse released more NBL than those isolated from a rat. In contrast, T. spiralis females isolated from a mouse produced fewer NBL than those isolated from a rat. Trichinella nativa and T. spiralis induced similar gene expression changes in the intestinal tissue of a selective host studied with whole-genome microarray on day five post infection (p.i)., even though the parasite burden caused by T. spiralis was significantly higher than that caused by T. nativa. When the two Trichinella-infected groups were pooled and compared with control animals, microarray data of the infected animals indicated nonspecific damage and an inflammatory response in the jejunal mucosa. Histopathological changes supported the microarray data. Trichinella spp. is highly prevalent in Finland; it is a risk for domestic animals and humans. Even low infection intensity can cause clinical signs or symptoms.Trichinella nativa on nematodeihin eli sukkulamatojen luokkaan ja Trichinella-sukuun kuuluva loinen. Trikinellalajit ovat maailmanlaajuisesti levinneitä ja voivat aiheuttaa trikinelloosiksi kutsutun sairauden sekä eläimissä että ihmisissä. Tässä väitöskirjassa tutkittiin sekä T. nativa –loisen että muiden trikinellalajien epidemiologiaa villieläimissä Suomessa. Lisäksi kuvattiin epätavallinen, kliinisiä oireita aiheuttava T. nativa –loisinfektio kotikissassa. Kahden eri trikinellalajin (T. nativa ja T. spiralis) aiheuttamaa vastetta isäntäeläimessä vertailtiin nk. valikoivassa isännässä (rotta) pyrkimyksenä selvittää se loisen elämänkierron vaihe, jossa puolustus loista kohtaan tapahtuu. Joka neljäs (24.8%) tutkituista 2483 lihansyöjistä kerätyistä näytteistä osoittautui trikinellapositiivisiksi. Loista esiintyi enemmän Etelä-Suomessa kuin Pohjois-Suomessa Neljä eri trikinellalajia (T. spiralis, T. nativa, T. britovi ja T. pseudospiralis) tunnistettiin käyttäen multiplex-PCR -tekniikkaa. Trichinella nativa oli yleisin (80.1%) Suomessa esiintyvä trikinellalaji. Kettu ja supikoira olivat tärkeimmät reservuaarieläimet, kun eläinlajin populaatiokoko, trikinellainfektion arvioitu prevalenssi ja infektion voimakkuus otettiin huomioon. Trikinellainfektio voi aiheuttaa myös kliinisiä oireita. Kotikissalla todettiin hoitoon vastaamaton haavauma silmäluomen alapuolella, ja haavauma-alueelta otetussa, patologille lähetetyssä kudosnäytteessä havaittiin tulehdus- ja arpikudosreaktion ympäröimä trikinellatoukka. Kissan seerumissa todettiin vasta-aineiden nousu trikinellaloista vastaan ELISA ja Western blotting –menetelmillä. Multiplex-PCR –menetelmän avulla lajiksi varmistettiin T. nativa. Yhden vuoden seuranta-aikana kissan alkuperäiselle haavauma-alueelle kasvoi ihonalainen massa, joka histopatologisessa kudostutkimuksessa osoittautui tulehdusreaktioksi, johon liittyi voimakas arpikudosmuodostus sekä arpikudossolujen koon ja muodon vaihtelua. Suun kautta annettaessa T. spiralis aiheutti rotalla 69 kertaa voimakkaamman infektion lihaksissa kuin T. nativa. Laskimoon annettaessa infektio oli 12 kertaa voimakkaampi. Tulosten perusteella puolustus trikinellaa kohtaan ei tapahdu pelkästään loisen suolistossa tai sen ulkopuolella tapahtuvassa elämänkierrossa. Osa näiden kahden trikinellalajin erilaisesta infektiivisyydestä rotalle voidaan selittää myös trikinellalajien erilaisella lisääntymiskyvyllä; T. nativa –naaraat, joiden hedelmöittyminen oli tapahtunut rotan suolistossa, tuottivat vähemmän poikasia kuin ne T. nativa –naaraat, jotka olivat hedelmöittyneet hiiren suolistossa. Trichinella nativa ja T. spiralis saivat aikaan samanlaisen geeniekspression muutoksen rotan suolistossa 5 päivää infektion jälkeen. Tämä todettiin käyttäen rotan koko genomin sisältävää mikroarray-tekniikkaa. Kun nämä kaksi trikinellainfektoitua rottaryhmää yhdistettiin ja verrattiin kontrolliryhmään, mikroarray-tulokset viittasivat epäspesifiseen vaurioon ja tulehdusreaktioon suoliston limakalvolla. Histopatologiset muutokset tukivat mikroarray-tuloksia, ohutsuolesta otetuissa kudosnäytteissä todettiin tulehdusmuutoksia sekä pintaepiteelin vaurio. Trikinellatartunta on hyvin yleinen suomalaisissa villieläimissä, se on riski sekä kotieläimille että ihmisille. Myös hyvin lievä infektiotaso voi aiheuttaa kliinisiä oireita

Prospective survey of neoplastic and non-neoplastic uterine disorders in 116 domestic rabbits (Oryctolagus cuniculus)

Background: Earlier studies indicate that the risk for uterine tumours in rabbits may be as high as 60-80%. This high occurrence and the need for routine neutering of non-breeding pet rabbits have recently been in the spotlight. Methods: This study aimed to describe and compare macroscopic and histopathological alterations in uteri collected from domestic rabbits of various ages neutered, deceased, or euthanized without a suspected uterine disorder (NoUD; n = 94) and from rabbits with a suspected uterine disorder (UD; n = 22). Results: In the NoUD group, uteri of 41 rabbits (44%) displayed histopathological findings and 12 rabbits (13%) had neoplasms. Samples from thirteen rabbits (14%) evinced histopathological findings with no macroscopic alterations. The most frequent diagnoses were cystic endometrial hyperplasia (26% of the 41 uteri), adenocarcinoma (9%), and polyps (5%). In the UD group, uteri from 21 (95%) out of 22 rabbits exhibited pathological alterations; in 2 (10%) of these, the changes (cystic endometrial hyperplasias) were seen only in histology. The most frequent diagnoses in the uteri of the UD group were cystic endometrial hyperplasia (77%) and adenocarcinoma (54%). Uterine malignant neoplasia affected 40% of all rabbits aged over 3 years, and the odds of a malignant uterine tumour in these rabbits were approximately 19-fold higher than in rabbits aged under 3 years. Conclusions and clinical relevance: Uterine disorders are common in domestic rabbits, even without a suspected uterine disease, and the risk of uterine neoplasia markedly increases after 3 years of age. A macroscopically normal uterus may have pathological changes and ovariohysterectomy should be therefore preferred over ovariectomy at least in older rabbits.Peer reviewe

Sarcocystis calchasi in a captive Patagonian conure (Cyanoliseus patagonus) in Finland

Sarcosystis calchasi is an emerging pathogen causing encephalitis in many avian species and has been documented in North America, Germany and Japan. In November 2019, a captive Patagonian conure (Cyanoliseus patagonus), kept in a zoological aviary in Finland, was euthanized due to acute respiratory distress. At necropsy, histopathological examination revealed numerous parasitic tissue cysts in the skeletal muscles and myocardium, chronic moderate multifocal lymphoplasmacytic and histiocytic meningoencephalitis and acute moderate multifocal purulent pneumonia caused by aspiration of foreign material. By light and transmission electron microscopy, tissue cysts had structures typical of Sarcocystis organisms. The ultrastructure of the cyst wall was compatible with S. calchasi and Sarcocystis columbae. S. calchasi-specific semi-nested polymerase chain reaction testing resulted in amplification of the internal transcribed spacer (ITS) gene, which had 100% identity with S. calchasi ITS sequences. This is the first report of S. calchasi in Fennoscandia and of a naturallyoccurring S. calchasi infection in a captive psittacine bird in Europe. Our finding suggests that captive psittacine birds kept in outdoor facilities may be at risk of S. calchasi infection throughout the Holarctic. (C) 2021 The Author(s). Published by Elsevier Ltd.Peer reviewe

Infection with Possible Novel Parapoxvirus in Horse, Finland, 2013

A horse in Finland exhibited generalized granulomatous inflammation and severe proliferative dermatitis. After euthanization, we detected poxvirus DNA from a skin lesion sample. The virus sequence grouped with parapoxviruses, closely resembling a novel poxvirus detected in humans in the United States after horse contact. Our findings indicate horses may be a reservoir for zoonotic parapoxvirus.Peer reviewe

Infection with possible novel parapoxvirus in horse, Finland, 2013

A horse in Finland exhibited generalized granulomatous inflammation and severe proliferative dermatitis. After euthanization, we detected poxvirus DNA from a skin lesion sample. The virus sequence grouped with parapoxviruses, closely resembling a novel poxvirus detected in humans in the United States after horse contact. Our findings indicate horses may be a reservoir for zoonotic parapoxvirus.</p

A Genome-Wide Association Study of Diabetic Kidney Disease in Subjects With Type 2 Diabetes

dentification of sequence variants robustly associated with predisposition to diabetic kidney disease (DKD) has the potential to provide insights into the pathophysiological mechanisms responsible. We conducted a genome-wide association study (GWAS) of DKD in type 2 diabetes (T2D) using eight complementary dichotomous and quantitative DKD phenotypes: the principal dichotomous analysis involved 5,717 T2D subjects, 3,345 with DKD. Promising association signals were evaluated in up to 26,827 subjects with T2D (12,710 with DKD). A combined T1D+T2D GWAS was performed using complementary data available for subjects with T1D, which, with replication samples, involved up to 40,340 subjects with diabetes (18,582 with DKD). Analysis of specific DKD phenotypes identified a novel signal near GABRR1 (rs9942471, P = 4.5 x 10(-8)) associated with microalbuminuria in European T2D case subjects. However, no replication of this signal was observed in Asian subjects with T2D or in the equivalent T1D analysis. There was only limited support, in this substantially enlarged analysis, for association at previously reported DKD signals, except for those at UMOD and PRKAG2, both associated with estimated glomerular filtration rate. We conclude that, despite challenges in addressing phenotypic heterogeneity, access to increased sample sizes will continue to provide more robust inference regarding risk variant discovery for DKD.Peer reviewe

Ménétrier-like disease in a Pointer with concurrent granulomatous gastritis, helicobacteriosis and leishmaniosis: a case report : a case report

BackgroundMenetrier-like disease is a rare hypertrophic canine gastropathy, reported in only seven dogs. Clinical signs are vomiting, anorexia and weight loss. Macroscopically, giant cerebriform gastric mucosal folds are typically seen in the corpus and fundus of the stomach. Histopathologically, fundic mucous cell hyperplasia and loss of parietal and chief cells are typical.Case presentationA nine-year-old spayed female Pointer had a history of intermittent vomiting, marked weight loss and hypoalbuminaemia. A gastroduodenoscopy was performed three times within three months with macroscopic changes remaining the same. The gastric mucosa of the corpus, fundus and proximal antrum was markedly irregular, with cerebriform mucosal folds. In the first gastric biopsies, histopathology revealed a moderate granulomatous gastritis, with a severe manifestation of Helicobacter-like organisms. Treatment for Helicobacter spp. decreased the vomiting slightly. The dog was diagnosed with concurrent leishmaniosis; the conventional anti-Leishmania treatment decreased the vomiting moderately, the hypoalbuminaemia resolved and the dog gained weight back to a normal body condition. Granulomatous gastritis was not present in the gastric biopsies after these treatments. The dog increased vomiting when palliative treatment (maropitant citrate, ondansetron and esomeprazole) was discontinued, and thus, full-thickness biopsies of the stomach were taken and Menetrier-like disease was diagnosed. The affected area was too large to be surgically removed; thus, palliative treatment was reinstated. The dog remained clinically well 39 months after the first clinical presentation.ConclusionsThis is the first report of Menetrier-like disease in a dog with a simultaneous manifestation of granulomatous gastritis, helicobacteriosis and leishmaniosis. The clinical signs decreased after treatment of helicobacteriosis and leishmaniosis, but vomiting remained probably as a sign of Menetrier-like disease. Treatment options for dogs are surgical removal of the abnormal area or palliative treatment. In humans, promising results for a cure have been shown with cetuximab treatment, a human monoclonal antibody, but no canine antibody is commercially available yet. The dog here was doing well 39 months after first presentation, which is the longest reported survival time for Menetrier-like disease with only palliative treatment in dogs. Full-thickness biopsies are preferred in macroscopic hypertrophic lesions of the stomach for better assessment of Menetrier-like disease.Peer reviewe

Ménétrier-like disease in a Pointer with concurrent granulomatous gastritis, helicobacteriosis and leishmaniosis: a case report : a case report

BackgroundMenetrier-like disease is a rare hypertrophic canine gastropathy, reported in only seven dogs. Clinical signs are vomiting, anorexia and weight loss. Macroscopically, giant cerebriform gastric mucosal folds are typically seen in the corpus and fundus of the stomach. Histopathologically, fundic mucous cell hyperplasia and loss of parietal and chief cells are typical.Case presentationA nine-year-old spayed female Pointer had a history of intermittent vomiting, marked weight loss and hypoalbuminaemia. A gastroduodenoscopy was performed three times within three months with macroscopic changes remaining the same. The gastric mucosa of the corpus, fundus and proximal antrum was markedly irregular, with cerebriform mucosal folds. In the first gastric biopsies, histopathology revealed a moderate granulomatous gastritis, with a severe manifestation of Helicobacter-like organisms. Treatment for Helicobacter spp. decreased the vomiting slightly. The dog was diagnosed with concurrent leishmaniosis; the conventional anti-Leishmania treatment decreased the vomiting moderately, the hypoalbuminaemia resolved and the dog gained weight back to a normal body condition. Granulomatous gastritis was not present in the gastric biopsies after these treatments. The dog increased vomiting when palliative treatment (maropitant citrate, ondansetron and esomeprazole) was discontinued, and thus, full-thickness biopsies of the stomach were taken and Menetrier-like disease was diagnosed. The affected area was too large to be surgically removed; thus, palliative treatment was reinstated. The dog remained clinically well 39 months after the first clinical presentation.ConclusionsThis is the first report of Menetrier-like disease in a dog with a simultaneous manifestation of granulomatous gastritis, helicobacteriosis and leishmaniosis. The clinical signs decreased after treatment of helicobacteriosis and leishmaniosis, but vomiting remained probably as a sign of Menetrier-like disease. Treatment options for dogs are surgical removal of the abnormal area or palliative treatment. In humans, promising results for a cure have been shown with cetuximab treatment, a human monoclonal antibody, but no canine antibody is commercially available yet. The dog here was doing well 39 months after first presentation, which is the longest reported survival time for Menetrier-like disease with only palliative treatment in dogs. Full-thickness biopsies are preferred in macroscopic hypertrophic lesions of the stomach for better assessment of Menetrier-like disease.Peer reviewe