Protective immunity induced by irradiated third-stage larvae of the filaria Acanthocheilonema viteae is directed against challenge third-stage larvae before molting.

Jirds (Meriones unguiculatus) were vaccinated with irradiated L3 third-stage larvae (L3) of Acanthocheilonema viteae, and the time required for killing of the challenge L3 was determined. The number of parasites recovered from vaccinated jirds was reduced to about 10% of the control values on the second day after challenge infection and later on. Histological studies revealed an eosinophil-rich infiltrate containing macrophages, neutrophils, and mast cells in the vicinity of the L3 on day 2 after challenge and destruction of the worms by day 4 after challenge. Ultrastructural studies confirmed these data and showed that eosinophils, macrophages, and mast cells were close to the L3 on day 2 after challenge. Flattening of the eosinophils onto the surface of the worms, degranulation of electron-dense material, and rupture of the L3 surface was observed on day 4 after challenge, followed by invasion of the inner of the worms by phagocytic cells. These data show that immune attack against the challenge L3 in vaccinated jirds is initiated between the first and the second day after challenge and that killing occurs around the fourth day after challenge, before the worms undergo their first molt.

Acanthocheilonema viteae: vaccination with irradiated L3 induces resistance in three species of rodents (Meriones unguiculatus, Mastomys coucha, Mesocricetus auratus).

Three species of rodents were immunized with 50 irradiated (35 krad) stage-3 larvae (L3) of the filaria Acanthocheilonema viteae and challenged with an infection of normal L3. The immunization induced a significant reduction of the worm burden developing from the challenge infection in all host species, the jird (Meriones unguiculatus), the multimammate rat (Mastomys coucha) and the golden hamster (Mesocricetus auratus). The induced resistance was highest in jirds (92.5 +/- 9.7) followed by golden hamsters (59.4 +/- 26.6) and multimammate rats (55.1 +/- 40.4). The time course of antibody response against antigens of L3, adult worms and microfilariae, as studied by ELISA, showed quantitative and qualitative differences between the species. The antibody response against L3 antigens in immunoblots was similar in all species. Only one of the golden hamsters developed an antibody response against the surface of vector derived L3, while sera of jirds and multimammate rats did not react with L3 surface.

A 41-kDa antigen of the rodent filaria Acanthocheilonema viteae with homologies to tropomyosin induces host-protective immune responses.

A purified 41-kDa protein of the rodent filaria Acanthocheilonema viteae was shown to protect jirds against a challenge infection. Subcutaneous immunization with the protein reduced the number of adult worms by up to 65% and the number of circulating microfilariae declined by up to 93% in these animals. The protein is located in the muscle tissues of adult worms and was identified as tropomyosin by N-terminal sequencing of the purified protein.

Acanthocheilonema viteae: vaccination of jirds with irradiation-attenuated stage-3 larvae and with exported larval antigens.

Jirds (Meriones unguiculatus) were immunized with irradiated (35 krad) stage-3 larvae (L3) of Acanthocheilonema viteae. The induced resistance against homologous challenge infection and the antibody response of the animals were studied. Immunization with 3, 2, or 1 dose of 50 irradiated L3 induced approximately 90% resistance. Immunization with a single dose of only 5 irradiated L3 resulted in 60.8% protection while immunization with a single dose of 25 L3 induced 94.1% protection. The protection induced with 3 doses of 50 irradiated L3 did not decrease significantly during a period of 6 months. Sera of a proportion, but not all resistant jirds, contained antibodies against the surface of vector derived L3 as defined by IFAT. No surface antigens of microfilariae or adult worms were recognized by the sera. Vaccinated animals had antibody responses against antigens in the inner organs of L3 and in the cuticle and reproductive organs of adult worms as shown by IFAT. Immunoblotting with SDS-PAGE-separated L3 antigens and L3-CSN revealed that all sera contained antibodies against two exported antigens of 205 and 68 kDa, and against a nonexported antigen of 18 kDa. The 205-kDa antigen easily degraded into fragments of 165, 140, 125, and 105 kDa which were recognized by resistant jird sera. Various antigens of adult worms, but relatively few antigens of microfilariae, were also recognized. To test the relevance of exported antigens of L3 to resistance, jirds were immunized with L3-CSN together with a mild adjuvant. This immunization induced 67.7% resistance against challenge infection and sera of the immunized animals recognized the 205- and 68-kDa antigens of L3.

Filariasis in Amerindians of Western Guyana with observations on transmission of Mansonella ozzardi by a Similium species of the amazonicum group

In order to conduct experimental infection studies on Mansonella ozzardi in local haematophagos Diptera, volunteers infected with this parasite were identified during a microfilaria survey of four Amerindian villages in the Pakaraima Mountains of Western Guyana, near the Brazilian border. M. ozzardi microfilariae were detected in blood smears from 8-21 percent of persons examined. They were also found in skin snips from 8/73 persons all of whom were positive by blood smear examination. No Onchocerca volvulus microfilariae were detected. Dipetalonema perstans infections were found in three of four villages but prevalence rates were only 1-8 percent. Man-baited catches of haematophagous Diptera made at the onset of the dry season in one of the villages yielded only three Simulium species. After the flies were engorged on infected volunteers, M. ozzardi larvae developed to the infective stage in 6-7 days in the most abundant species, a member of the Simulium amazonicum group. Man-biting rates of up to 156 per 15-minute period were recorded for this species in midday collections along riverbanks near one of the villages. Developing filariae, including infective larvae of M. ozzardi, were also found in wild-caught flies. It was concluded that this Simulium species is a vector of M. ozzardi in the study area (Summary)

Implant chemotherapy of experimental filariasis.

The in vitro diffusion of the organophosphate famphur from polydimethylsiloxane (PDS) capsules into plasma and their effects on Litomosoides carinii and Dipetalonema witei in jirds was studied. The in vitro rate of diffusion per 24 hours was constant and was directly proportional to the capsule lumen surface area and inversely proportional to the capsule wall thickness. One capsule implanted subcutaneously into each jird almost completely eliminated the microfilaremia of L. carinii while in situ (5 weeks) but had no effect on the levels of microfilaremia of D. witei. The adults of both species were unaffected. The capsules were well tolerated by the jirds and little tissue response to them was noted. The possibilities of using PDS-incapsulated drugs for prophylactic chemotherapy of canine and human filariasis is discussed.