The BALB/C mouse infected with Brugia pahangi has been evaluated as a model for the selection of filaricidal compounds with activity against immature worms. Mice were infected by the intraperitoneal inoculation of 50 infective larvae and candidate compounds were administered by the intraperitoneal (i.p.), subcutaneous or oral route once daily from day 4 to day 8 post infection. Animals were examined on days 29 to 32 post infection. Variation in the larval recoveries from undrugged mice within and between experimental groups limited the value of drug assessments based upon percentage worm recoveries. The infection rate of undrugged mice was 85% over-all, range 60 to 100%. Using the infection rate of drugged v. undrugged animals as the criterion of activity the test has been evaluated with a series of standard nematicidal compounds.. Lcvamisolc and the benzimidazole carbamatcs, mebendazole, flubendazole and fenbendazole given i.p. at lOmg/kg daily were active in this screen whilst DEC, DEC-N-oxidc, ivcrmcctin, amoscanatc, mctrifonatc and suramin were inactive at the dosages tested. No retardation of growth or morphological abnormalities were observed in worms from the drugged mice.

Oxidative deamination of various biogcnic monoamines by Ascaridia galli monoaminc oxidase (MAO) was blocked by different mammalian MAO inhibitors, namely, iproniazid, trans-PcP, nialamide and pargyline and the blockade was observed to be time as well as concentration dependent. The binding of inhibitors with chick ascarid MAO was of the irreversible type and the nature of the inhibition was competitive. Pargyline showed lowest I50 (8µM) and K1 (12µM) values. Chlorgyline and deprenyl at 100µM concentration inhibited MAO by about 60 and 40% respectively, indicating the presence of both type A and type B MAO in A. galli.

Mastomys natalensis wcrc infected percutancously with 250 cercariae of Schistosoma mansoni and treated effectively with 5 x 50 mg amoscanatc/kg body-weight 12–16 (1), 28–32 (10,56–60 (111) and 101–105 days p.1. (IV) respectively. Levels of reaginic antibodies (RAb) and homocytotropic IgG antibodies (GAb) were assessed by passive cutaneous anaphylaxis tests (PCA) and compared with those in infected, untreated animals. In untreated animals RAb were first detected in the 6th week p.i. Maximum titres around 1:80 were reached after 100 days. High levels persisted until the end of the experiment 185 days p.i. RAb did not develop after treatment I. After treatmcnt 11 only low PCA titres occurred. After treatment 111 the time course was similar to the controls but levels were reduced. Treatment IV did not interfere with the occurrence of specific RAb.

In the case of GAb, independent of any treatment, after a first peak of PCA titres in the 5th week either a negative pattern or only very low titres were found in week 7. In untreated infected Mastomys GAb levels increased thereafter to maximum titres of about 1:80 at day 70. Later than 100 days p.i. relatively constant titres were observed. The second rise of antibody levels did not occur after early treatment. After treatment 11 only low transient titres developed. Animals treated in the early patcncy (III) showed reduced PCA titres and were negative at the end of the observation period. Treatment given 101 to 105 days pi. rather enhanced the development of GAb.

Laboratory investigations were designed to study the influence of temperature, pH and oxygen tension on the growth of Arthrobotrys oligospora, a nematode-trapping microfungus. Experiments were performed to evaluate the potential role of A. oligospora in destroying third-stage larvae of Cooperia spp. on agar plates and in cattle faeces. The fungus had a growth rate optimum at 23°ree;C and pII 6. Anaerobic cultivation for 23 hours at 23°ree;C and 39°ree;C inhibited fungal growth, but it did not destroy the fungus, which regained growth upon a subsequent shift to aerobic conditions at 23°ree;C. Under experimental conditions in petri-dishes containing agar, the nematode-trapping efficiency of the fungus was striking in that 100% of a population of third-stage larvae of Cooperia spp. was captured within three days of the experiment. The trapping efficiency in faeces was shown to depend upon the inoculation level. At a concentration of approximately 2500 conidia per g faeces, 99% of the larvae were destroyed. The possibilities of using nematode-trapping fungi in controlling animal-parasitic nematodes arc discussed.

From May 1982 until September 1983 samples of soil and herbage were collected from a paddock grazed from May to October 1982, and for two short periods between May and July 1983, by sheep infected with gastro-intestinal nematodes. Few infective larvae were recovered from the soil although appreciable numbers of larvae were recovered from the herbage. Infective larvae of Trichostrongylus vitrinus in faeces buried in the soil of grass plots, at a depth of 10cm, each month from April 1982 until March 1983, migrated on to the herbage at all times of the year, few remaining in the soil. The significance of the soil as a reservoir of infective larvae is discussed.

The fourth-stage larvae and adults of Ascaris suum were studied as they developed in the pig intestine from 11 to 22 days after infection. This is a period of rapid growth, in which both sexes increase approximately ten-fold in body length. Further examination of females showed the length increase to be positively allometric with respect to body diameter. The genital primordium in early fourth stage is at the same relative position along the length of the body as it is in the newly hatched larva. During development from fourth stage to adulthood the greater growth of the posterior part of the worm causes the relative position of the developing vulva to shift anteriad.

The response of hamsters to Ancylostoma ceylanicum was studied between days 13 and 200 after infection. The infected hamsters showed signs of anaemia, particularly between the 13th and 60th days. A significant loss in body-weight in the infected animals was also observed during this period. Serological studies with agar gel-diffusion, counterimmunoclectrophoresis and indirect hacmagglutination tests revealed positive reac tions between the 20th and 60th days followed by a negative response in the latent period between the 60th and 200th days of infection, counterimmunoclectrophoresis test remained positive for a period of 150 days in this experimental model.

Toxocara canis larvae were cultured in vitro in medium containing [35S-]methionine for six days. The medium and the larval tissues were analysed for biosynthetically labelled polypcptides by sodium dodecyl sulphate polyacrylamide gel electrophoresis and autoradiography. Immunoprecipitates with positive and negative human antiserum were similarly analysed, using Staphylococcus aureus to absorb immunocom plexes. The larvae secrete biosynthctically labelled polypeptides into the medium, with three major polypcptides of molecular weights between 99 and 110 x 103 the major constituents. Both of these react strongly with human IgG in human positive scra. Many polypeptidcs become labelled in the larval tissue, but only one polypeptidc with similar molecular weight to the ES antigens, strongly reacted with human IgG.

Snails, provisionally identified as Bulinus tropicus, on the basis of chromosome number, egg protein profile, AcP and 118DH enzymes of the digestive gland, and radular morphology, from Lochinvar National Park, Zambia have been demonstrated to transmit Schistosoma margrebowiei naturally. The identification of the unpaired male schistosomcs was confirmed by PGM and AcP analyses. The observations confirm earlier epidemiological predictions, and add another species of mollusc to the two, B. forskalii and B. scalaris, known to be natural intermediate hosts of S. margrebowiei.

Test mice have been selectively reared for high (H) or low (L) immune responses to Nematospiroides dubius. After secondary infection with N. dubius, the L mice voided ten times as many eggs in their faeces as the II mice, and at necropsy, 71% versus 20% of the inoculum of N. dubius were recovered as adult worms from the L and II mice respectively. Furthermore, N. dubius were more fecund in the L than in H mice. High or low immune responsiveness was not restricted to N. dubius infection in these mice but was also observed during Toxocara canis infection. The migration of T canis larvae from gut via the liver to skeletal muscle and CNS was inhibited in H versus L mice. Many more larvae were recovered from the livers of II compared with L mice which was indicative of greater immunity in the H mice. The protective immune response in H compared with L mice to both N. dubius and T canis included pronounced cosinophilia and elevated antiparasite antibody titres.

Gross changes in the size of the secondary lymphoid organs were studied during infection with the nematode parasite Nematospiroides dubius. In the strong responder NIH strain, the wet weight of the mesenteric lymph nodes (MLN) increased rapidly following infection with 400 larvae to peak on day 28 at approximately three times the resting weight. Enlargement of the spleens was also marked but regression to normal size took place when the MLN had achieved maximum size. In contrast in C57BL/10 mice, a slow responder strain, the enlargement of the MLN following infection was relatively slow, and there was no evidence of the regression of the spleen, once maximum enlargement had been achieved.

When adult worms were removed by anthclmintic, the enlarged MLN and spleens returned rapidly to normal size. I lowever, in mice infected with irradiated larvae (25 krad) the MLN stayed enlarged, despite the absence of adult worms but the spleens of these mice returned to normal size fairly rapidly. It was suggested that irradiated worms survive, perhaps as arrested larvae in the intestinal tissue, for a fairly long time, thereby providing a continual stimulus for the MLN.

Attempts were made to manipulate specific responses of baboons to protect them from infection with Schistosoma mansoni. In Experiment 1, cosinophilia was induced in naive baboons with Trichinella spiralis larvae given intravenously before intraperitoneal injection of globulin fractions from S. mansoni-infected baboon sera and subsequent percutancous exposure to S. mansoni cercariac. In Experiment 2, baboons with 8- or 32-week-old primary S. mansoni infections received T spiralis i.v. before an S. mansoni challenge. In experiments 3 to 5 respectively, naive baboons received intramuscularly before challenge: formalin-fixed S. mansoni schistosomula, with Bordetella pertussis as an adjuvant; a preparation of S. mansoni adult worm teguments; and a preparation of NE-immune complexes obtained from S. mansoni-infected rat sera, with Freunds Complete Adjuvant. Minor, but statistically insignificant, protection was obtained in Experiments 2 (32-week infections) and 3, but was far less than that given by intact, irradiated living vaccines. There are signs on the horizon of non-living vaccines protecting rodents against S. mansoni infection and it would be prudent, as with drugs, to test these in primates before proceeding to man. The results of our experiments, though essentially negative, should help the design of any future vaccine trials in primates.