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Biomedical subjects

R F Sturrock

Publications and source records attributed to R F Sturrock.

At least 73 records · Page 4Linked to original sources
PubMed1982

Schistosoma haematobium in the baboon (Papio anubis): effect of vaccination with irradiated larvae on the subsequent infection with percutaneously applied cercariae.

Groups of five baboons were vaccinated three times at approximately six-weekly intervals at a rate of 1,000 organisms per kg of gamma-irradiated Schistosoma haematobium larvae. Five vaccines were tested: 3 and 20 Krad cercariae applied percutaneously; fresh 3 and 20 Krad mechanically transformed schistosomula injected intramuscularly; and cryopreserved 20 Krad schistosomula injected intramuscularly. These five groups and an unvaccinated control group were challenged percutaneously with 7,500 S. haematobium cercariae three months after the last vaccination. The efficacy of the vaccines was judged by faecal egg excretion, and by adult worm and tissue egg recoveries at necropsy 4.5 months after challenge. Significant protection, with 64 to 89% reductions in worm burden and parallel reductions in egg production, was achieved by all but the cryopreserved vaccine, although egg production was not significantly reduced in those female worms which did mature. Cercariae tended to give more protection than schistosomula and 20 Krad more protection than 3 Krad. No significant pathology could be detected in an additional baboon vaccinated with 20 Krad schistosomula but not challenged with cercariae. This is an encouraging result for the development of a live vaccine against S. haematobium.

Animals↗
PubMed1982

Non-specific cell mediated immunity in patients infected with Schistosoma mansoni in Kenya.

Parameters of in vitro cell-mediated immunity (CMI) have been measured in the local Kenyan population infected with Schistosoma mansoni. Lymphocyte responses to the non-specific T cell mitogens Concanavalin A (Con A) and Phytohaemagglutinin (PHA) were reduced in about 60% of schistosomiasis patients. Lymphocytes from control uninfected, and S. mansoni-infected donors formed equal numbers of spontaneous rosettes with sheep red blood cells, indicating that there was no over-all reduction in the percentage numbers of T cells in the schistosomiasis patients.

Adolescent↗
PubMed1981

Heat-labile and heat-stable anti-schistosomular antibodies in Kenyan schoolchildren infected with Schistosoma mansoni.

Two in vitro cytotoxicity assays using 51Cr-labelled Schistosoma mansoni schistosomula were performed on serum samples collected from 91 schoolchildren infected with S. mansoni from Machakos District, Kenya. One assay, which is believed to detect IgE/antigen complexes, uses unheated serum and human monocytes; the other, believed to detect IgG antibodies, uses heat-inactivated serum and unpurified peripheral blood leucocytes. Analysis of the data was complicated because the children were drawn from two separate studies and the data was extremely variable, probably because of the manner in which infections are acquired under natural conditions. There was a strong, positive regression of intensity of infection on age of the children, and evidence that IgG, but not IgE, activity was related to intensity of infection. There was no clear-cut relationship of IgE and IgG activities with the age of the children, and little evidence of any correlation between IgE and IgG activities within individual children. The implications of this latter dissociation and the possibility of either mechanism acting as the effector mechanism for concomitant immunity in man are discussed in the light of these results.

Adolescent↗
PubMed1981

The effect of praziquantel on Schistosoma haematobium, S. japonicum and S. mansoni in primates.

Baboons infected with S. haematobium and vervet monkeys infected with S. japonicum were treated orally with different dosage regimens of 2-cyclohexylcarbonyl-1,2,3,6,7,11b-hexahydro-4H-pyrazino[2,1-a]isoquinolin-4-on e(praziquantel, EMBAY 8440, Biltricide) and were autopsied and perfused 3--4 months after treatment. The results suggest that a single oral dose of 75--100 mg/kg body weight is likely to be effective against S. haematobium in the baboon. Female worms of S. haematobium are apparently more susceptible to the compound than male worms. The classic hepatic shift of adult schistosomes was observed in all the primates, but histopathological studies showed that numerous worms also died in situ, only a few being found in the lungs. The results obtained with praziquantel against S. japonicum in the vervet monkey show that a complete cure was obtained in the animal given 50 mg/kg on five consecutive days. A predominant characteristic in the pathology of the animals given a curative dose of praziquantel was the total resolution of cellular reaction and fibrosis in the tissues containing known numbers of dead residual eggs. In the baboons infected with S. haematobium, the ureters and bladders had recovered their functional integrity and in the vervet monkeys infected with S. japonicum, a similar resolution of pathology in the liver and bowel was apparent.

Animals↗
PubMed1980

An immunosuppressive factor in the serum of baboons (Papio anubis) infected with Schistosoma mansoni.

Serum taken from baboons infected with Schistosoma mansoni was able to suppress in vitro reactivity of normal baboon lymphocytes. The concanavalin A response was significantly suppressed by such serum, whereas the specific suppression of the phytohaemagglutinin response was minimal. Serum from S. mansoni infected donors also depressed the mixed lymphocyte reactions to xenogeneic targets, but did not affect the specific transformation of lymphocytes stimulated with a parasite Ag. Significant suppressive activity occurred in the baboon serum from 4 to 11 weeks after the initial infection. Serum from animals with a chronic infection of 6-42 months, did not suppress in vitro cell-mediated immunity. The suppressive factor was heat-stable, non-dialysable and, following ultracentrifugation of the suppressive serum, was found to be present in the high mol. wt fraction. From these studies, it is suggested that the immunosuppressive factors are immune complexes, which appear in the serum of the baboons following their infection with this blood parasite.

Animals↗
PubMed1980

Functional studies on purified eosinophils and neutrophils from patients with Schistosoma mansoni infections.

Unpurified peripheral blood leucocytes or purified eosinophils and neutrophils from patients with schistosomiasis and from normal individuals were compared for their ability to interact with antibody coated schistosomula of Schistosoma mansoni. There was no difference in the ability of buffy coat cells or neutrophils from patients and from normal individuals to mediate antibody-dependent 51Cr release from labelled schistosomula. However, eosinophils from patients were significantly better than those from normal individuals in causing antibody-dependent 51Cr release. This enhanced activity of eosinophils from patients with schistosomiasis was found to correlate with the intensity of their infection as judged by faecal egg counts. Eosinophils from patients also contained a higher proportion of cells with detectable Fc receptors than those from normal individuals. It is suggested that the difference in the behaviour of eosinophils from patients and from normals may reflect an 'activated' state of these cells in the infected individuals.

Adolescent↗
PubMed1979

Schistosome infection rates in field snails: Schistosoma mansoni in Biomphalaria pfeifferi from Kenya.

Six collections of Biomphalaria pfeifferi were made in the Nairobi and Machakos areas of Kenya. Individual cercarial shedding (Method A) showed that 6.9% (65/938) of the snails had mature 'patent' Schistosoma mansoni infections (range 3.1--34% in the six collections). Crushing (Method B) about one-third of the remaining snails detected no additional mature infections but yielded 1.4% (four snails from one collection) with secondary sporocysts from immature 'prepatent' infections. Weekly shedding observations for five weeks (Method C) on the remainder of the snails showed that 6.9% (40 snails from four collections--range 1.5--30%) shed cercariae maturing from infections immature at the time of collection. As Method B detected no cercariae, Method A apparently detected all 'patent' infections reliably, despite the stress suffered by the snails before examination. Method C was simpler and more efficient than Method B in the detection of infections which were immature at the time of collection. Judging from the rate at which infections matured in Method C, field snails in heavily endemic areas are subjected to pulses of infection rather than to a continuous flow of miracidia. The 'patent' infection rate was not correlated to the 'prepatent' infection rate. Some of the implications of these findings to mathematical models of schistosome transmission are discussed.

Animals↗
PubMed1978

Schistosoma mansoni in the Kenyan baboon (Papio anubis): the development and predictability of resistance to homologous challenge.

Groups of baboons were exposed to primary infections of either 500 or 2,000 Schistosoma mansoni cercariae per baboon (c.p.b.). Five from each infection level and five uninfected baboons were challenged with 2,500 c.p.b. at one of four intervals of time after primary infection and killed ten weeks later, together with unchallenged appropriate primary infection controls. Primary faecal egg excretion was related to the cercarial dose, showing some systematic fluctuations during the 78 weeks of the experiment. Challenge infections increased faecal egg excretion in certain cases only. Faecal and tissue egg production were usually suppressed in the challenge worms. In contrast to less heavily infected, challenge-control baboons bearing primary infections, the challenged baboons had minimal gross pathology and there were no deaths due to acute schistosomiasis from the challenge infection. Over-all resistance to reinfection was low and unrelated to the age or intensity of the primary infections. However, seven baboons yielded less than 50% of the expected challenge worms. An in vitro assay, measuring anti-schistosomula antibody and peripheral leucocyte cytotoxic activity, successfully identified the in vivo immune status at thetime of challenge of 14/18 baboons tested. The in vivo significance of the immunological mechanism upon which the test is based is discussed in relation to possible future baboon and human studies.

Animals↗
PubMed1978

The mechansim of antibody-dependent, eosinophil-mediated damage to schistosomula of Schistosoma mansoni in vitro: a study by phase-contrast and electron microscopy.

A characteristic sequence of events has been identified by phase-contrast and electron microscopy during antibody-dependent, eosinophil-mediated damage to schistosomula of Schistosoma mansoni in vitro. Human eosinophils initially adhere to the intact schistosomulum and then, in the presence of antibody, flatten and spread very intimately over the parasite's surface. Subsequently, dense material similar to the contents of the lysosomal granules of the eosinophils appears in the extracellular space between the eosinophil and the schistosomulum, probably following fusion of the granules with the plasma membrane of the cell. Eventually all the eosinophils adhering to the parasite are completely degranulated and large amounts of the dense material are observed on the surface of the schistosomulum. This release of granular material from the eosinophils is followed by structural changes in the schistosomulum, starting with vacuolation of the inner layer of the tegument, followed by removal of the tegument, often in the form of large sheets. Subsequently the tegument disintegrates and the fragments are phagocytosed by other eosinophils which have not degranulated. Eosinophils then attach to the exposed muscle layers of the schistosomula and participate in the further degradation of the parasites by phagocytosing fragments of muscle fibres and other cellular components. This sequence of events is compared with published observations of the damage induced by various combinations of antibody, complement and effector cells in vitro, and of cell-mediated damage to schistosomula in vivo, and it is concluded that the observations described in the present paper may reflect a process of destruction of schistosomula in the immune host.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1978

Cytotoxicity of human and baboon mononuclear phagocytes against schistosomula in vitro: induction by immune complexes containing IgE and Schistosoma mansoni antigens.

Normal human blood monocytes, pre-incubated at 37 degrees C with sera from patients infected with Schistosoma mansoni, strongly adhered to S. mansoni schistosomula in vitro, whereas no significant adherence was induced by sera from uninfected individuals. Comparable adherence occurred with normal baboon blood monocytes or peritoneal macrophages when these cells were incubated with sera from S. mansoni-infected baboons. Adherence of macrophages to schistosomula was associated with damage to the larvae, as estimated by a 51Cr release technique. Neither adherence nor cytotoxicity was induced by pre-incubation of the schistosomula, instead of the monocytes, with immune serum. The relevant factor in immune serum was heat-labile, but was not a complement component. Absorption and ultracentrifugation experiments showed that immune complexes, containing S. mansoni-specific IgE antibody and soluble parasite antigens, produced monocyte or macrophage adherence and cytotoxicity. Similar observations have been reported previously in the rat model. Since the production of large amounts of IgE is a predominant feature of schistosome infections in man and experimental animals, it is possible that this new mode of mononuclear phagocyte activation could act as an immune effector mechanism against S. mansoni.

Animals↗
PubMed1977

Antibody-dependent eosinophil-mediated damage to 51Cr-labeled schistosomula of Schistosoma mansoni: damage by purieid eosinophils.

After earlier observations that antibody-dependent, cell-mediated damage to 51Cr-labeled schistosomula can be ablated by pretreatment of a mixed preparation of human peripheral blood leukocytes with an anti-eosinophil serum and complement, we investigated the cytotoxic effects of eosinophil-enriched cell preparations. Preparations containing up to 98.5% eosinophils and devoid of neutrophils were effective in mediating antibody-dependent damage to schistosomula. Preparations enriched in mononuclear cells or in neutrophils, and devoid of eosinophils, were inactive. Eosinophils from some patients with eosinophilia induced by schistosomiasis were less active on a cell-to-cell basis than cells from normal individuals. The possibility that such cells were initially blocked by immune complexes was considered, and it was found that reasonable cytotoxicity by purified eosinophils from patients with eosinophilia could be generated by overnight cultures. A possible requirement for cooperation between eosinophils and other cell types was also studied. Lymphocytes, neutrophils and monocytes failed to enhance eosinophil-mediated cytotoxicity. These results provide further evidence that the eosinophil is the only cell in man responsible for antibody-dependent, complement-independent damage to schistosomula in vitro. Eosinophils from individuals, however, differ in their cytotoxic potential by a mechanism yet to be elucidated. The possible relationship of these findings to immunity in vivo is discussed.

Animals↗