Early prognosticators of later TSPO-PET-measurable microglial activation in multiple sclerosis.

BACKGROUND: Factors driving increased innate immune cell activation in multiple sclerosis (MS) brain are not well understood. As higher prevalence of microglial/macrophage activation in association with chronic lesions and diffusely in the normal appearing white matter predict more rapid accumulation of clinical disability, it is of high importance to understand processes behind this. Objective of the study was to explore demographic, clinical and paraclinical variables associating with later positron emission tomography (PET)-measurable innate immune cell activation. METHODS: PET-imaging using a TSPO-binding [11C]PK11195 was performed to evaluate microglial activation in patients with relapsing-remitting MS aged 40-55 years with a minimum disease duration of five years (n = 37). Medical records and diagnostic MR images were reviewed for relevant early MS disease-related clinical and paraclinical parameters. RESULTS: More prominent microglial activation was associated with higher number of T2 lesions in the diagnostic MRI, a higher immunoglobulin G (IgG) index in the diagnostic CSF and Expanded Disability Status Scale (EDSS) ≥ 2.0 five years after diagnosis. CONCLUSION: The number of T2 lesions in MRI, and CSF immunoglobulin content measured by IgG index at the time of MS diagnosis associated with later TSPO-PET-measurable innate immune cell activation. This suggests that both focal and diffuse early inflammatory phenomena impact the development of later progression-related pathology.

Outbreak of parasitic peritonitis in reindeer in Finland.

In 2003, there was an outbreak of peritonitis in reindeer in the southern and middle part of the Finnish reindeer herding area caused by the filarioid nematode Setaria species. In the province of Oulu, the proportion of reindeer viscera condemned owing to parasitic lesions increased from 4.9 per cent in 2001 to 40.1 per cent in 2003. In 2004, the focus of the outbreak moved approximately 100 km north. A total of 260 adult and pre-adult Setaria species nematodes were collected for morphological and molecular studies. The parasite was indistinguishable in terms of morphology and molecular biology from Setaria tundra. Samples of parasites were also collected from wild cervids. In elk, only a few cases of pre-adult encapsulated S tundra nematodes were detected on the surface of the liver but there was no peritonitis. Two roe deer had S tundra nematodes in their abdomen but no peritonitis. Of 34 wild forest reindeer, 21 had changes associated with S tundra. At meat inspection of the affected reindeer carcases, the changes observed included ascites, green fibrinous deposits, adhesions, and live and dead S tundra nematodes. There were histological lesions of granulomatous peritonitis with lymphoplasmacytic and eosinophilic infiltration. No specific bacterial growth was found. The parasitic infection had no significant effects on the pH or the organoleptic quality of the meat. There was a significant positive correlation between the worm count and the degree of peritonitis (P<0.001) and a negative correlation between the degree of peritonitis and the thickness of the back fat layer (P=0.015).

The efficacy of flubendazole against different developmental stages of the poultry roundworm Ascaridia galli in laying hens.

Infection with the poultry roundworm Ascaridia galli has increased in European countries due to the ban on battery cages. This study was conducted in two commercial laying hen flocks (F1 & F2) on different farms in central Sweden. The aims were to (1) investigate the efficacy of flubendazole (FLBZ, 1.43 mg/kg administered in drinking water for 7 days) against adult and larval stages including histotrophic larvae of A. galli, and (2) determine how long it took before the flocks were reinfected after deworming. Accordingly, 180 randomly selected hens were sacrificed before drug administration (bd), on day 3 and 7 during drug administration (dd), and on a weekly basis for up to five weeks post drug administration (pd). Intestinal contents and cloacal materials of each hen plus pooled faecal samples from manure belts were investigated to assess the worm burden and the parasite egg per gram faeces (epg). Additionally, drinking water, and serum and gastrointestinal digesta content samples obtained from ten treated animals were analyzed by HPLC to measure FLBZ and its reduced (R-FLBZ) and hydrolyzed (H-FLBZ) metabolites. No parasite eggs were observed in cloacal samples on day 21 and 28 pd on F1 and on day 21 pd on F2. The epg in manure decreased by 65% and 88% on day 3 dd and by 99% and 97% on day 35 pd on F1 and F2 respectively. Mean FLBZ concentrations quantified in duodenal contents ranged between 0.50 and 0.79 µg/g. Although, no histotrophic larvae were found dd, they reappeared one week pd (7 ± 7 F1, 0.5 ± 0.5 F2). Adult worms were found in both flocks before drug administration (44 ± 20 F1, 35 ± 25 F2), on day 3 dd (4 ± 3 F1, 2 ± 2 F2), and then not until day 35 (0.2 ± 0.6) on F1 and day 28 (0.4 ± 0.9) pd on F2. Thus, the only period in which no A. galli were found was on day 7 dd. Although FLBZ was highly efficient our results indicate that the birds were reinfected already within one week pd.

Redescription of Besnoitia tarandi (Protozoa: Apicomplexa) from the reindeer (Rangifer tarandus).

Besnoitia tarandi tissue cysts were found in naturally-infected reindeer (Rangifer tarandus) from Finland. Infectivity of its tissue cysts, bradyzoites, and tachyzoites to animals and cell culture was studied. The bradyzoites and tissue cysts were not infectious to out-bred mice, rabbits or gerbils. When fed tissue cysts, neither cats nor dogs excreted oocysts. However, the parasite was lethal to interferon-gamma gene knock out mice irrespective of the route of inoculation. The parasite was grown successfully in African Green Monkey cells from tissues of two reindeer for the first time. Non-dividing, uninucleate tachyzoites from smears from cell cultures were 5.6 x 1.4 microm (4.5-7.4 x 1.0-1.9, n=50) in size. Longitudinally-cut bradyzoites in tissue sections measured 7.4 x 1.3 microm (6.5-7.8 x 1.0-1.6, n=30). Ultrastructurally, tachyzoites and bradyzoites were similar to those in other Besnoitia species, and in particular to parasites described from cattle (Besnoitia besnoiti) and equids (Besnoitia bennetti) in that their bradyzoites lacked enigmatic bodies. Based on comparative analysis of three portions of nuclear ribosomal DNA (the small and large subunits and the first internal transcribed spacer) B. tarandi was found to be more closely related to the other congeners described from ungulates. The parasite was formally redescribed and specimens deposited in the US National Parasite Collection.