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Biomedical subjects

F W Jennings

Publications and source records attributed to F W Jennings.

At least 55 records · Page 3Linked to original sources
PubMed1983

Relapsed parasitaemia following chemotherapy of chronic T. brucei infections in mice and its relation to cerebral trypanosomes.

Mice infected with Trypanosoma brucei can be easily cured using the available trypanocidal drugs, provided treatment is given soon after the infection; however, if infection is allowed to continue for some time then it is extremely difficult to obtain a permanent cure, and after an aparasitaemic period the infection eventually relapses. It has been shown that a relatively small number of infective trypanosomes in the brain have escaped the action of the drug and these are able to replicate and eventually they re-establish a circulating parasitaemia. The number of infective trypanosomes remaining after chemotherapy varied according to the stabilate of T. brucei, but using the stabilate T. brucei GVR 35 there were up to, 5,000 infective trypanosomes 2 days after treatment, and this rapidly increased up to 50,000 trypanosomes at 7 days. Infected mice on histological examination exhibited a mild meningitis and this was exacerbated by Berenil therapy and 7 days posttreatment the mice had an acute meningoencephalitis. It would appear that if the infective trypanosomes are completely eliminated from the brain this exacerbated reaction does not occur. It has been found that combined treatment of chronic T. brucei infections with either diminazene aceturate or suramin followed by 5-substituted nitroimidazoles at appropriate dose levels will completely eliminate the infective trypanosomes from the brain and the mice are permanently cured.

Animals↗
PubMed1982

The possible use of Trypanosoma musculi infection in mice as a screening test for potential Trypanosoma cruzi-active drugs.

The ability of a range of trypanocidal drugs, including a number known to be active in Trypanosoma cruzi infections were tested against Trypanosoma musculi infections in the mouse. The ability of these drugs, particularly in their ability to eliminate the "cryptic phase" of T. musculi infections remaining in the kidneys, was investigated and their activity against this phase of T. musculi largely paralleled their known activity against T. cruzi infections. It is suggested that this could be used as a preliminary screening test for potential T. cruzi-active drugs.

Animals↗
PubMed1982

Relapse of monomorphic and pleomorphic Trypanosoma brucei infections in the mouse after chemotherapy.

Infections in mice were initiated with trypomastigotes from two lines of Trypanosoma brucei derived from the same primary isolated. Infections with one line were initiated by inoculation of metacyclic trypomastigotes from infected tsetse flies and the resulting infections were pleomorphic. The other line had been passaged 32 times in rodents and inoculation of bloodstream trypomastigotes gave rise to monomorphic infections. In both infections there were high levels of parasitaemia until death up to 4 weeks later if the infection was untreated. It was shown that after chemotherapy with 40 mg/kg diminazene aceturate (Berenil) relapses occurred in both types of infection after an aparasitaemic period of 2--3 weeks. Further, it was shown that 3 days after chemotherapy, brain tissue but neither spleen, liver nor blood was capable of transferring infection to normal recipient mice. There were two major differences in the response of the two infections to chemotherapy. First, treatment of the pleomorphic infection as soon as day 6 after infection resulted in a subsequent relapse while the monomorphic infection had to be at least 12 days old at the time of treatment before occurred. Second, following treatment of the pleomorphic, but not of the monomorphic infection there was an early transient recrudescence of low numbers of trypanosomes which were found to be non-infective to recipient mice. The early transient relapse was followed by a further aparasitaemic period and then the late continuous relapse characterised by large numbers of infective trypanosomes.

Amidines↗
PubMed1982

The use of Erlangen diamidine 98/202 in relapsing Trypanosoma brucei infections in mice.

Mice infected with T. brucei GVR 23/1 or T. brucei GVR 35/1 for 21 days were treated with the Erlangen diamidine 98/202 (6-amidino-2-[4' amidino-phenyl] thionaphthene-dilacate) at either 5 mg/kg or 35 mg/kg. At both these dose levels the parasites were initially cleared from the circulation although the infections eventually relapsed due to reinvasion from the central nervous system. If the 98/202 therapy is followed by treatment with 5-nitroimidazole only a small number of mice are permanently cured. Adverse reactions, especially at the 35 mg/kg dose level, were noted in one experiment. The Erlangen diamidine given to infected mice three days after infection was able to permanently cure both Trypanosoma brucei stabilates.

Amidines↗
PubMed1982

Observations on the infectivity and pathogenicity of three isolates of Ostertagia spp sensu lato in calves.

After experimental infection of three groups of calves with three different defined isolates of Ostertagia spp sensu lato a marked variation in the infectivity and degree of pathological change was noted. The most highly infective and pathogenic isolate contained approximately 30 per cent O leptospicularis in addition to O ostertagi (70 per cent) and a negligible number of Skrjabinagia lyrata. The other two isolates consisted solely of O ostertagi (approximately 90 per cent) and S lyrata (approximately 10 per cent) and showed comparable infectivity and pathogenicity to that commonly recorded. The greater pathogenicity of the isolate containing O leptospicularis was attributed to the higher infectivity and the greater damage caused to the gastric mucosa by individual parasites when compared with O ostertagi.

Abomasum↗
PubMed1982

Field study on the epidemiology and pathogenicity of different isolates of bovine Ostertagia spp.

The epidemiological features of three different isolates of bovine Ostertagia spp under similar initial levels of larval challenge were compared in the field. Two of the isolates, consisting mainly of Ostertagia ostertagi, and a low proportion of Skrjabinagia lyrata conformed in epidemiological behaviour with those investigated by previous workers, though the worm burdens which established did not give rise to the expected clinical signs. The third isolate behaved in a different way, yielding very high faecal egg counts which were followed by high pasture larval counts, heavy worm burdens and severe clinical disease. This isolate, while consisting mainly of O ostertagi and a few S lyrata, also contained a proportion of O leptospicularis, and it is suggested that this species may influence the dynamics of the host-parasite relationship in bovine ostertagiasis.

Animals↗
PubMed1981

Immunological clearance of 75Se-labelled Trypanosoma brucei in mice. III. Studies in animals with acute infections.

Using trypanosomes labelled with [75Se]-methionine a series of experiments was conducted to investigate antibody production in mice with acute fulminating T. brucei infections. As measured by the hepatic uptake of radiolabelled parasites, we were unable to demonstrate any evidence of antibody-mediated uptake by the liver in such mice. It was concluded that this was not due to impaired macrophage function but was caused by the inability of antibody production to cope with the massive parasitaemias produced by rapidly-replicating infections so that effective opsonization of the parasites did not occur. In contrast, a train of trypanosome which causes a more chronic infection, although initially having a similar replication, although initially having a similar replication rate, subsequently switched t a slower one and thereby allowed antibody to reach levels which permitted effective opsonization. There was no evidence that the parasite caused any significant suppression of antibody responses in these acute infections since inoculation with trypanosomes of one stock at the same time as vaccination with irradiated organisms of a second stock did not prevent the development of antibody to the latter, as measured by the hepatic uptake of radiolabelled parasites.

Acute Disease↗
PubMed1980

Genetic resistance to Trypanosoma congolense infections in mice.

The mechanisms of genetic resistance or "trypanotolerance" to infection with Trypanosoma congolense were investigated in two strains of mice. One strain C57BL, is outstandingly resistant to most stabilates of T. congolense and can survive for over 80 days, whereas CFLP, in common with most other strains, generally succumbs in less than 20 days. Evaluation of several pathophysiological and immunological parameters showed that after infection both strains initially developed similar levels of parasitemia, anemia, biochemical derangement, and immunosuppression. The most outstanding difference was after day 8 postinfection, when the susceptible strain (CFLP) sustained high levels of parasitemia (10(9) trypanosomes per ml) until death 2 to 4 days later, whereas the resistant strain (C57BL) showed a marked decrease to less than 10(6) trypanosomes per ml by day 10 postinfection. Clear evidence that this was associated with the presence of trypanocidal antibody in the resistant mice was provided by the results of an infectivity neutralization test on serum collected from each strain at 10 days postinfection. Chronically infected C57BL mice showed declining waves of parasitemia and a slow restoration of most hematological and biochemical indexes to near normal levels by 80 days postinfection, although at this stage they remained immunosuppressed.

Anemia↗
PubMed1980

Immunological clearance of 75Se-labelled Trypanosoma brucei in mice. II. Mechanisms in immune animals.

Using trypanosomes labelled with [75Se]-methionine a series of experiments was conducted to investigate the respective roles of antibody, macrophage activtion and complement in the removal of trypanosomes from the circulation of immune mice. It was found that clearance in such animals is largely accomplished by antibody-mediated hepatic phagocytosis, which, at least in passively immunized animals, is dependent on opsonization involving C3. No evidence was found to suggest that intravascular lysis or activated macrophages are involved in immune clearance.

Animals↗
PubMed1979

Observations on ostertagiasis in young cattle over two grazing seasons with special reference to plasma pepsinogen levels.

The epidemiology of ostertagiasis in south west Scotland was studied in groups of cattle grazed through two successive grazing seasons separated by a period of winter housing. Towards the end of the first grazing season (September) the numbers of infective larvae (L3) on the pasture had increased to high levels (up to 24,000 L3 per kg) which resulted in high faecal egg counts, worm burdens, plasma pepsinogen levels and the occurrence of clinical ostertagiasis in the calves. By late spring (May) at the onset of the second grazing season, there was an almost complete mortality of the overwintered L3 on the pasture followed by the appearance of moderately high numbers of a new population of L3 in September (up to 9000 L3 per kg). The latter increase in the numbers of L3 was reflected by negligible faecal egg counts, low worm burdens and a moderate elevation of plasma pepsinogens in the second year animals. It therefore seems that although young cattle acquire a good immunity to Ostertagia ostertagi after one season at grass the small infections established in the early part of the second season are capable of contaminating the pasture to levels which could be dangerous for susceptible stock. An allergic reaction in the abomasal mucosa could be the basis of the elevated pepsinogens present in the second year animals.

Animals↗
PubMed1979

Immunosuppression in bovine trypanosomiasis: studies with louping-ill vaccine.

The antibody response to louping-ill virus vaccine was examined in mice infected with Trypanosoma brucei and T congolense, and in Ethiopian cattle experimentally infected with T brucei, T congolense and T vivax. In mice the antibody response was completely suppressed, while in cattle infected with T congolense and T vivax the antibody response to the vaccine was only 10 per cent that of uninfected animals. In contrast, the response of cattle infected with T brucei was not significantly reduced, and this was attributed to their relatively light and transient parasitaemias. Trypanocidal chemotherapy (diminazine aceturate) administered on the same day as vaccination largely restored the competence of the immune response of both mice and cattle infected with T congolense. The use of such drugs should be considered when cattle are vaccinated in trypanosome endemic areas.

Animals↗
PubMed1979

Immunological clearance of 75Se-labelled Trypanosoma brucei in mice. I. Aspects of the radiolabelling technique.

A reliable and simple technique for the in vivo labelling of Trypanosoma brucei with [75Se]-methionine was developed. Between 97 and 99% of the radioactivity was protein bound in the trypanosomes and spontaneous elution in vitro was less than 10% over 4 h. The fate of the labelled trypanosomes after i.v. injection into normal and immune mice was studied. Whilst the vast majority of parasites remained in the circulation of normal animals they rapidly disappeared from the blood of immune animals. In the latter the liver was found to be the principal site of phagocytosis removing over 50% of the radiolabelled parasites within 15 min of injection.

Animals↗
PubMed1978

Attempted protection of zebu cattle against trypanosomiasis using a multi-stabilate vaccine.

The protective value of double vaccination with 11 recently isolated stabilates of Trypanosoma congolense given either as live or dead organisms, followed by trypanocidal therapy, was assessed in zebu cattle subsequently challenged by nine of the original stabilates. Both vaccination regimens failed to prevent the animals becoming parasitaemic and eventually succumbing to the infection, although the mean survival times and prepatent periods of the calves which received the live vaccine were longer than those of both the groups which had received the dead vaccine and the challenge controls.

Animals↗