Setaria digitata in advancing our knowledge of human lymphatic filariasis.

Setaria digitata is a filarial parasite that causes fatal cerebrospinal nematodiasis in goats, sheep and horses, resulting in substantial economic losses in animal husbandry in the tropics. Due to its close resemblance to Wuchereria bancrofti, this nematode is also frequently used as a model organism to study human lymphatic filariasis. This review highlights numerous insights into the morphological, histological, biochemical, immunological and genetic aspects of S. digitata that have broadened our understanding towards the control and eradication of filarial diseases.

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).

Immune response of electroeluted detergent soluble 29 kDa antigen from Setaria digitata (Von Linstow).

Filariasis is one of the typical parasitic infections which cause immune suppression during the course of infection in both humans and experimental animals. A 29 kDa protein isolated from detergent soluble antigen of S. digitata showed maximum inhibition of cell mediated immune response. The heat inactivated 29 kDa protein was found to be devoid of property of suppression of immune response in the host. Histological study of spleen of BALB/C mice immunized with 29 kDa protein showed changes in regions of spleen such as follicle, trabeculae, capsule, reticuloendothelial cells and eosinophils. The 29 kDa protein, the most reactive of the detergent soluble proteins produced partial suppression of immune response, thereby contributing to the factors responsible for the survival of filarial parasites in hosts.

Necrosis of lung epithelial cells by filarial parasitic protein via an early induction of c-H-ras and TNF alpha expression.

The direct interaction of filarial proteins with lung epithelial cells was examined to determine the possible mechanism of inducing cell death, an event that is observed in patients with tropical pulmonary eosinophilia. Exposure of lung epithelial cells to filarial parasitic proteins, Brugia malayi (BmA), Setaria digitata (Sd), and recombinant filarial protein (pGT 7) in vitro for more than 2 days, causes the appearance of DNA fragments both in the cytoplasm and culture supernatants, while no fragmentation was observed in the untreated controls. The release of DNA fragments both in the cytoplasm and the culture supernatants simultaneously, indicates that cell death is induced by a necrotic event rather than apoptosis. Fluorescent-labelled studies also indicate the fragmentation of DNA increasing in a time-dependent manner. Normal cellular function is controlled through several oncogenes. The modulation of specific proto-oncogenes like myc, ras and TNF alpha during exposure to filarial parasitic proteins reveal elevated levels of expression of ras and TNF alpha as early as 2 hours, implicating their involvement prior to DNA fragmentation leading to pathogenesis.

Setaria digitata microfilaraemia in Mastomys coucha: an animal model for chemotherapeutic and immunobiological studies.

Intraperitoneal implantation of adult gravid females of the bovine filarial parasite, Setaria digitata in Mastomys coucha was found to induce microfilaraemia lasting for about 125 days. The microfilariae (mf) could be detected as early as 4 days post-implantation (p.i.) and peak levels of about 30 mf in 20 microliters of blood were observed by 21 days. A significant positive correlation was found between mf density and the body weight of recipients pre-implantation. The implanted adult worms were generally viable only for less than 1 week. Implantation resulted in a significant decrease in total leucocytes and erythrocytes, induction of eosinophilia, splenomegaly and anti-erythrocyte autoantibodies. The microfilariae in circulation developed into 3rd-stage infective larvae (L3) when fed onto Aedes aegypti (refm, Liverpool strain). The mf in circulation were found to be eliminated by oral administration of diethylcarbamazine citrate, indicating the usefulness of this model for screening potential anti-microfilarial drugs. During the microfilaraemic phase, priming with tetanus toxoid (TT) resulted in significantly decreased production of anti-toxin levels indicating a state of generalized immunosuppression. Induction of antibodies to various fractionated antigenic components of adult parasites could be demonstrated by enzyme immunoassay (EIA) in M. coucha implanted with live or cold-stunned adult worms. The S. digitata-M. coucha model thus is found amenable to perform chemotherapeutic and immunobiological investigations in experimental filariasis.

Periorchitis after tetramisole treatment in bulls implanted with Setaria labiatopapillos.

Thirteen mixed-breed beef bulls, 1 to 4 years old, were used to determine the effect of live and dead filarial nematodes, Setaria labiatopapillosa, placed in the vaginal cavity of the testes. When dead worms were used, granulomatous lesions developed on the tunica vaginalis parietalis in 7 of 8 testes. The lesions were similar to those seen in some clinical cases of periorchitis. Similar lesions developed in 5 of 6 testes after live worms were implanted in the vaginal cavity of the testes and tetramisole (8 mg/kg) was injected subcutaneously 6 days after implantation. When live worms were implanted and tetramisole was not given, lesions developed in 3 of 6 testes. It was concluded that the granulomatous reaction was a local response to dead or killed S labiatopapillosa.