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Biomedical subjects

G S Nelson

Publications and source records attributed to G S Nelson.

At least 55 records · Page 3Linked to original sources
PubMed1979

Further observations on immunization of sheep against Schistosoma mansoni and S. bovis using irradiation-attenuated schistosomula of homologous and heterologous species.

This paper describes further characteristics of the immunization of sheep against schistosomes using live, irradiation schistosomula. Sheep immunized with a non-virulent strain of Schistosoma mattheei were protected against a more virulent strain of the same species for over a year. As there was no evidence that the irradiated parasites were able to persist this long, it was concluded that the vaccine had induced a sterile resistance. Heterologous vaccination, using irradiated S. mattheei schistosomula to immunize against S. bovis or irradiated S. mansoni schistosomula to immunize against S. mattheei, failed to induce any protection.

Animals↗
PubMed1979

Immunization of mice with gamma-irradiated intramuscularly injected schistosomula of Schistosoma mansoni.

The parameters involved in the induction of resistance against Schistosoma mansoni by injection of irradiated, artificially transformed schistosomula were studied in mice. Single intramuscular injections of 500 schistosomula exposed to radiation doses in the range 2.3 to 160 krad. resulted in significant protection (in the range 20 to 50% as assessed by reduced worm burdens) against a challenge infection administered at intervals from 3 to 24 weeks post-vaccination. However, schistosomula irradiated with 20 krad. consistently resulted in better protection than those exposed to either higher or lower radiation doses despite the persistence of stunted adults from the infections irradiated with 2.3 krad. Vaccination with 40 krad. schistosomula resulted in significant protection in terms of reduced worm and tissue egg burdens and increased survival following lethal challenge. Varying the number of irradiated schistosomula, the frequency and route of their administration, the site of challenge and the strain of host all failed to enhance the level of resistance. However, percutaneously applied, irradiated cercariae were found to be more effective in stimulating resistance (60%) than intramuscularly injected, irradiated schistosomula (40%).

Animals↗
PubMed1979

Successful vaccination of cats against Brugia pahangi with larvae attenuated by irradiation with 10 krad cobalt 60.

Cats were vaccinated by the inoculation on 10 occasions of approximately 300 larvae of Brugia pahangi which had been irradiated with 10 krad cobalt 60. They were challenged on 3 occasions with normal larvae of either B. pahangior B. patei. The vaccinated cats were resistant to challenge as demonstrated by either longer pre-patent periods or failure to become microfilaraemic and by having fewer third, fourth or adult worms than normal controls. Although the vaccination procedure was unpractically heavy these results lend encouragement to the possibility of developing vaccines against filarial infections.

Animals↗
PubMed1978

Studies with Brugia pahangi. 20. An investigation of 23 anthelmintics using different screening techniques.

23 anthelmintics were tested against Brugia pahangi microfilariae and infective larvae in vitro and in Aedes aegypti infected with B. pahagi and jirds (Meriones unguiculatus) infected with a B. pahangi/patei hybrid. There was little correlation between the results obtained in vitro and in infected insects and the results obtained in these tests gave no indication of the activity in jirds. Three of the compounds were macrofilaricidal in jirds and these were tested in cats infected with B. pahangi. One of these--5-benzamido-2(4-thiazolyl)-benzimidazole--was macrofilaricidal in cats and it is suggest that it should be tested in other filarial systems. It is concluded that the insect and in vitro tests are not good primary screens for filaricidal activity.

Aedes↗
PubMed1978

Studies with Brugia pahangi. 15. Cobalt 60 irradiation of the worm.

Infective larvae of Brugia pahangi were irradiated at 10, 25 or 45 krads by means of a Cobalt 60 source. In cats, 10 krads caused the worms to be stunted and sterile but allowed them to become 5th stage, migrate posteriorly into the afferent lymphatic, and produce pathology. 25 krads prevented the worms from developing beyond the early fourth stage and from migrating away from the popliteal lymph node. No gross pathological reacions were evident. 45 krads produced the same effects as 25 krads but the longevity of the worms was much reduced.

Animals↗
PubMed1978

Hybridization between Brugia patei, B. pahangi and sub-periodic B. malayi.

Virgin females of Brugia malayi, B. pahangi and B. patei were mated with males of species other than their own to determine whether they would hybridize. Microfilariae were produced in all but one cross (that between B. pahangi males and B. malayi females). Hybrid infective larvae, produced in mosquitoes and inoculated intraperitoneally into jirds, grew to adults but these were unable to produce microfilariae because hybrid males did not produce spermatozoa. Hybrid females were fertile and produced microfilariae when crossed with males of their parental species.

Animals↗
PubMed1977

Modification of the pathogenicity of Schistosoma mattheei for sheep by passage of the parasite in hamsters.

Border Leicester X Suffolk sheep infected with a strain of S. mattheei maintained in hamsters do not develop the same pathological changes as Romney Marsh sheep infected with the same strain of parasite before hamster passage. To determine the cause of this reduced pathogenicity, five Romney Marsh sheep were each infected with 10 000 cercariae of the hamster-passaged parasite and five with 10 000 cercariae of a S. mattheei strain from Onderstepoort, South Africa, passaged exclusively through sheep. Striking pathological and parasitological differences were found between the two strains. Infection with the "sheep" strain was lethal, whereas infection with the "hamster" strain produced little evidence of clinical disease. By 13 weeks post-infection the mean body weight of the sheep infected with the sheep strain had declined by 15% compared with both the uninfected controls and the sheep infected with the hamster strain, and the mean PCV was lowered to 20% in the sheep strain infected animals. Egg production began at seven weeks with the sheep strain, faecal counts rising to more than 300 e.p.g., whereas only two of the sheep infected with the hamster strain passed eggs in the faeces (at nine weeks) and the maximum egg count was 50 e.p.g. Twice as many adult worms of the sheep strain were recovered, and, although the number of eggs found in the tissues "per worm pair" was not significantly different, overall egg production was higher for the sheep strain; also more of the sheep strain eggs were deposited in the intestines. Similar parasite differences were seen in a supplementary study in mice and it seemed that "attenuation" of the parasite had occurred, presumably due to its maintenance in hamsters. Histopathological observations and faecal egg counts both indicated an inability of hamster strain eggs to penetrate the intestinal lumen; this was probably important in reducing the pathogenicity of the hamster strain.

Animals↗
PubMed1977

Immunization of sheep against a virulent strain of Schistosoma mattheei using a strain of S. mattheei attenuated by hamster passage.

We have previously described the characteristics of a relatively non-pathogenic laboratory strain of S. mattheei, attenuation of which was apparently caused by passage in hamsters. We now show that chronic infection with this avirulent strain largely protects sheep from the manifestations of acute schistosomiasis when challenged with a virulent strain of S. mattheei. Four sheep were each infected with 10 000 cercariae of the avirulent strain and, together with four wormfree sheep, challenged 63 weeks later with 10 000 S. mattheei cercariae of a pathogenic strain. Four more sheep acted as uninfected controls. Following challenge, the animals were weighed and bled weekly for PCV and serum protein determinations, and egg counts were carried out fortnightly on faeces taken from the rectum. Red cell and albumin turnover were monitored for two weeks immediately before challenge and for a similar period before necropsy, when the adult worms were recovered by perfusion and tissues sampled for histopathology and egg counting. The unvaccinated sheep developed severe disease 6-12 weeks after exposure characterised by marked anaemia, hypoalbuminaemia and hyper-gamma globulinaemia coinciding with the passage of blood-stained faeces and progressive inappetence. In the vaccinated sheep, there was an even earlier rise in gamma globulins, but the other clinico-pathological changes were generally slower to devleop and much milder in severity. The parasitological data showed that although this was partly due to a reduction in the establishment of the challenge worm population the main factor was probably a reduction in the fecundity of these worms.

Animals↗
PubMed1976

Immunisation of baboons against Schistosoma mansoni using irradiated S. mansoni cercariae and schistosomula and non-irradiated S. rodhaini cercariae.

In an attempt to develop a non-pathogenic procedure for immunising baboons against S. mansoni, groups of five baboons were exposed to three doses of 5000 6 Kr-irradiated S. mansoni cercariae or to similar numbers of normal S. rodhaini cercariae and challenged at week 15 with 500 normal S. mansoni cercariae. Faecal egg counts, worm and tissue egg counts, and histopathological examination, showed that neither of the immunising schedules had produced significant protection. In the second experiment baboons were injected by the intramuscular route with 31000 schistosomula of S. mansoni in three doses and the irradiation dose was reduced to near the minimum required for worm sterilisation (2-1--2-4 Kr). Challenge with 3500 normal cercariae of S. mansoni 21 weeks after the first immunising dose again showed no significant protection, although reductions of 20--30% were found in egg and worm counts resulting from the challenge. These results indicate that it may be difficult to develop an effective live vaccine for S. mansoni unless the antigenicity of the immunising larvae can be greatly increased.

Animals↗
PubMed1976

Immunisation of sheep against Schistosoma mattheei using either irradiated cercariae or irradiated schistosomula.

Irradiated cercariae, irradiated schistosomula, or heterologous infections were used to vaccinate sheep against Schistosoma mattheei infection. In the first experiment four doses of 10(4) S. mattheei cercariae irradiated at 6Kr were administered to sheep by percutaneous infection at 4 week intervals. This induced a 74% reduction in a challenge infection compared to control sheep while only 13% protection was achieved in a third group of sheep immunised with normal cercariae of the heterologous parasite S. mansoni. No significant differences were seen in histopathology of the liver of any of the sheep but the pathological changes were more severe in the large and small intestines of sheep vaccinated with the heterologous parasite. In the second experiment with irradiated cercariae only one or two immunising exposures were used. The degree of protection in the adult worm load (9-11%) was not significant and no significant differences were noticed in the pathology of the vaccinated and control animals. In the third experiment four doses of irradiated organisms were used to vaccinate five groups of sheep: 3Kr or 6Kr cercariae were administered by percutaneous infection; 6Kr skin-transformed schistosomula were administered by intra muscular injection; the same 6Kr skin-transformed schistosomula were given by intravenous injection and 6Kr syringe transformed schistosomula were administered by intramuscular injection. The degree of protection (determined as the reduction in worm burden) achieved by these different procedures was respectively 72%, 61%, 77%, 56% and 78%. These results indicate the possibility of making a live vaccine against ovine schistosomiasis and show that effective immunisation is not dependent on the presence of a mature worm infection or on cercarial penetration of the skin by the immunising infection.

Animals↗
PubMed1976

Acquired resistance to Schistosoma haematobium in the baboon (Papio anubis) after cercarial exposure and adult worm transplantation.

Observations were made on the development of acquired resistance to Schistosoma haematobium in the baboon following immunization with cercariae by the percutaneous route and by the transplantation of adult worms into the mesenteric veins. In the first experiment six baboons were immunized with 1000 S. haematobium cercariae given percutaneously. They were challenged with 10 000 cercariae given 73 weeks later and the results were compared with a similar infection in non-immunized animals. The results showed that the baboon can develop a strong resistance to reinfection with S. haematobium. The manifestations of the immunity were (i) the absence of any increase in egg output after challenge (ii) the substantially lower level of adult worms and eggs in the tissues of the immunized baboons compared with the challenge control animals (iii) a reduction in the egg laying capacity of the residual worms and (iv) the virtual absence of gross pathology and the mild lesions seen in the tissue sections of all the immunized animals. The depression in egg laying of the worms was confirmed by transplanting them into non-immune baboons. This experiment indicated that the non-egg-laying worms in the immune baboons were not irreversibly damaged since they survived, some even migrating to the vesical and ureteric vessels, and egg-laying was rapidly resumed after transplantation. A further experiment was designed to see if a similar degree of immunity could be produced by an adult worm infection without previous exposure to cercariae or schistosomula. The immunization dose consisted of 50-100 S. haematobium worm pairs which were transplanted into the mesenteric veins of each of six baboons and the animals were challenged percutaneously with 7000 cercariae 35-55 weeks later. There was little difference in the worm burdens of the immunized and control animals but the worms in the immunized baboons produced fewer eggs and the pathology seen in these animals was much milder than in the challenge control animals suggesting that some degree of resistance to reinfection was produced by the transplanted worms.

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