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Biomedical subjects

R F Sturrock

Publications and source records attributed to R F Sturrock.

At least 55 records · Page 3Linked to original sources
PubMed1988

Longitudinal studies on human schistosomiasis.

A major difficulty in understanding the epidemiology of human schistosomiasis has been to distinguish between acquired immunity and reduced exposure as possible reasons for an observed decline, in older individuals, of levels of superinfection or of reinfection after chemotherapy. A series of studies of Schistosoma mansoni infections in Kenya has been undertaken to approach this problem, by investigation of intensities of reinfection after treatment of individuals whose levels of contact with contaminated water is subsequently observed. Intensities of reinfection are highest among younger children, thereafter declining sharply. This decline can be attributed only in part to age-related changes in the duration and nature of exposure; there is also evidence for the development of an acquired resistance to reinfection that is dependent both on age and on previous experience of infection, and that may be immunologically mediated. Evidence has been obtained that the slow development of this acquired immunity with age may be associated with the early development and subsequent slow decline of inappropriate immune responses that 'block' the effect of potentially protective responses. Implications of these findings for immunological intervention through vaccination are discussed.

Adult↗
PubMed1988

Human antibody responses to Schistosoma mansoni: the influence of epitopes shared between different life-cycle stages on the response to the schistosomulum.

Sera from 120 Kenyan schoolchildren who were infected with S. mansoni were individually examined, using an enzyme-linked immunoabsorbent assay (ELISA), for the presence of IgG and IgM antibodies reactive with antigens derived from adult worms, the outer membrane of the schistosomulum or from the parasite egg. In addition, antibodies against more purified egg antigens, an egg stage-specific glycoprotein preparation and a polysaccharide egg antigen known to share epitopes with the schistosomular surface were measured in ELISA, as were antibodies reactive with trichloroacetic acid-soluble and periodate-insensitive antigens derived from the outer membrane of schistosomulum and antigens shed when schistosomula were cultured in vitro. IgG subclass responses to the unfractionated egg antigen were also measured. The results from each of these assays were compared with the results of each other assay and with the number of parasite eggs excreted by each child, using Spearmans rank correlations. These comparisons revealed a number of statistically significant positive correlations. IgG4 anti-egg antibodies correlated better with intensity of infection than did other IgG subclasses. Total IgG responses against polysaccharide antigens did not correlate with intensity of infection as well as IgG responses against other antigens; epitopes shared between the schistosomulum surface and the adult worm were different to those shared with the parasite egg; and, there was antigen-directed restriction of IgG subclass responses to some egg and adult worm antigens which carried these shared epitopes. It is argued that this might have a qualitative effect on the nature of the antibodies directed against the schistosomulum by infected individuals and therefore have important consequences for the outcome of a subsequent exposure to infection with the same parasite.

Adolescent↗
PubMed1988

Predisposition of humans to infection with Schistosoma mansoni: evidence from the reinfection of individuals following chemotherapy.

In a study of faecal egg counts of Schistosoma mansoni from 359 people of all ages from a rural Kenyan community, a positive association was demonstrated between infection intensity in individuals before treatment and reinfection intensity in the same individuals 9 months after treatment in certain age groups of the sampled population. Consequences and possible causes of these observations are discussed in terms of the epidemiology and control of schistosomiasis.

Adolescent↗
PubMed1988

Observations on the implications of pathology induced by experimental schistosomiasis in baboons in evaluating the development of resistance to challenge infection.

Liver samples from 10 Schistosoma mansoni-infected baboons all yielded eggs but neither their egg counts nor duration of infection (less than 226 weeks) correlated with the slightly elevated liver collagen levels or minimal histological fibrosis observed. Approximately 10% of inert 9 and 15 micron diameter microspheres injected into the mesenteric veins of 2 baboons with acute, challenge S. mansoni infection reached their lungs (mainly 9 micron microspheres). Lung egg recoveries over 1000 were significantly less common among 175 baboons exposed once to S. mansoni infections than among 56 baboons exposed more than once. Among 221 S. mansoni-and S. haematobium-infected baboons, female worm, total tissue egg and lung egg recoveries were significantly correlated with each other but not with liver or (where available) spleen weights. Liver and spleen weights were strongly correlated with total body weight. Baboons did not develop significant liver fibrosis, even after prolonged schistosome infections. However, some liver 'leakiness' developed during acute primary and challenge infections, allowing small inert particles and eggs to pass to the lungs, but this 'leakiness' was not associated with resistance to challenge. In contrast to mice, such resistance in baboons cannot, therefore, be explained simply in terms of pathological changes due to previous infections.

Animals↗
PubMed1987

Immunity after treatment of human schistosomiasis mansoni quantitative and qualitative antibody responses to tegumental membrane antigens prepared from adult worms.

Quantitative antibody responses of individual Kenyan children to a tegument membrane preparation from adult schistosomes have been studied by enzyme-linked immunosorbent assay. Qualitative differences between patients were examined by electrophoretic fractionation of the membrane preparation followed by Western blotting analysis. All individuals had antibodies to the preparation, the level increasing twofold shortly after chemotherapy and declining to pre-treatment levels by 6 months. Susceptible children had significantly higher levels of antibody than resistant individuals at 12 and 18 months after chemotherapy. Antibody levels were positively associated with patient age (particularly over the range 8-12 years at the first bleed after chemotherapy) and the logarithm of pre-treatment egg excretion. The strongest association was observed between initial antibody level and subsequent levels. A total of 47 distinct antigens was detected in the membrane preparation. The major antigens were detected equally strongly by sera from both susceptible and resistant groups of children. At the outset the resistant group responded more strongly to 35%, and more weakly to 15%, of the antigens than the susceptible group. At the end of the study the figures were reversed, being 21% and 38% respectively, probably reflecting the reflecting the reinfection of the susceptible group. 3 antigens of molecular mass 100, 50 and 27 kDa were exceptions to the trend, being detected more strongly by the resistant than the susceptible group at one or more later times. It was concluded that the differences in total antibody level to the tegument membrane preparation were insufficient to account for the resistant or susceptible status of the children.

Animals↗
PubMed1987

A histological study of skin reactions of baboons to Schistosoma mansoni schistosomula.

A histological study was undertaken of the cellular reaction in the skin of baboons challenged with cercariae of Schistosoma mansoni. Control animals with no previous schistosome infection were compared with baboons that had infections of varying duration. In animals infected for 10 weeks no striking inflammatory reaction was seen, the histological picture being very similar to that of the control animals. After 8 months of infection the hosts developed a strong cellular response to the invading schistosomula. The predominant cells in these reactions were eosinophil leucocytes which sometimes closely adhered to degenerating schistosomula. However, some unaffected schistosomula were found close to these intense cellular reactions, suggesting that schistosomula possess varying ability to resist the host's immunological attack.

Animals↗
PubMed1987

Parasitological evaluation of curative and subcurative doses of 9-acridanone-hydrazone drugs against Schistosoma mansoni in baboons, and observations on changes in serum levels of anti-egg antibodies detected by ELISA.

Derivatives in the class of 9-acridanone-hydrazones were found to be highly active against Schistosoma mansoni in baboons. Single doses of 25 mg/kg were fully effective. Data are presented showing changes detected by ELISA in antibody levels against schistosome eggs which correlated positively with the effect of chemotherapy. This approach may help to evaluate the effects of treatment of human schistosomiasis where the detection of low egg counts is problematic.

Acridines↗
PubMed1987

Immunity after treatment of human schistosomiasis mansoni. III. Long-term effects of treatment and retreatment.

Group mean Schistosoma mansoni reinfection patterns are presented for 2 years after treatment with oxamniquine in 1981 of over 100 9- to 16-year-old Kenyan schoolchildren, and for one year after retreatment in 1983 with either oxamniquine or praziquantel when most (nearly 700) infected people in the whole community were treated. Quality control confirmed comparable Kato egg counts throughout the study. Continuing transmission after 1981 raised prevalence to nearly its original level within 6 months, but intensity remained suppressed throughout the 2 year follow-up and very few children reacquired heavy infections (greater than 400 eggs/g). Age and sex had significant effects: reinfection diminished with age, especially among boys--a pattern not apparently attributable to differential water contact. Children with heavy pretreatment infections tended to develop heavy reinfections but this trend was not statistically significant on a group basis, nor were similar trends during the period of less pronounced transmission following the 1983 community treatment. Oxamniquine was equally effective in children receiving it in both 1981 and 1983, and the efficacy of praziquantel resembled that of oxamniquine. In this area of Kenya, repeated chemotherapy will be needed to contain transmission, probably annually or biennially, unless supplemented with other, effective control measures. These findings confirm the beneficial effects of treating even a limited segment of a community at intervals of a year or more without necessarily stopping transmission. They are also compatible with recent findings on potential immune mechanisms in man.

Adolescent↗
PubMed1987

Evidence for predisposition of individual patients to reinfection with Schistosoma mansoni after treatment.

Statistical analysis of the relationship between intensities of infection before treatment and during reinfection after treatment in a sample of 119 Kenyan schoolchildren demonstrated a positive association, indicating that the individuals differed consistently in their tendency to become infected. This association was stronger in young children but the trend was detectable in older individuals. Possible reasons for this variation and for its apparently greater influence in younger age groups are discussed.

Adolescent↗
PubMed1986

A review of the use of primates in studying human schistosomiasis.

Rodents, useful models for studies of human schistosomiasis not ethically possible in man, are not satisfactory in every respect. Primates, in many ways better models than rodents, though too expensive for general use, remain invaluable for testing the relevance of rodent findings to man. Higher primates such as chimpanzees are ideal models but, as endangered species, should only be used for critical studies for which lower, nonhuman primates are unsuitable.

Animal Diseases↗
PubMed1985

A note on the efficacy of a new class of compounds, 9-acridanone-hydrazones, against Schistosoma mansoni in a primate--the baboon.

Five 9-acridanone-hydrazone compounds were tested against moderately heavy Schistosoma mansoni infections in baboons. They were administered as a single oral dose at a rate of 50 mg/kg body-weight. Compared with results from an untreated control baboon, four of the compounds showed high levels of activity judged by the reduction or elimination of faecal egg production, adult worms and tissue eggs.

Animals↗
PubMed1985

Attempts to manipulate specific responses to induce resistance to Schistosoma mansoni in Kenyan baboons (Papio anubis).

Attempts were made to manipulate specific responses of baboons to protect them from infection with Schistosoma mansoni. In Experiment 1, eosinophilia 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 percutaneous exposure to S. mansoni cercariae. 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 IgE-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.

Animals↗
PubMed1985

Attempts to induce resistance to Schistosoma mansoni and S. haematobium in Kenyan baboons (Papio anubis) using non-specific immunostimulants.

Non-specific immunostimulants were used in an attempt to protect baboons from infection by schistosomes. Subcutaneous vaccination with cord factor (4.50 mg) and muramyl dipeptide (4.56 mg) 6 days before percutaneous exposure to 3000 Schistosoma haematobium cercariae/baboon (c.p.b.) failed to protect naive baboons: baboons with a 7-month-old, 5000 c.p.b. S. haematobium primary infection had developed too strong a natural immunity to detect any protection attributable to vaccination. Subcutaneous vaccination with 0.4 ml of Bacillus Calmette-Guerin (BCG, 1-8 X 10(8) colony forming units/ml) 4 days before exposure to 1000 c.p.b. S. mansoni gave a significant (38%) reduction in worm load compared with controls. However, vaccination with 0.8 (intramuscular) and 0.2 (intradermal) ml of BCG 11 days before exposure to S. mansoni 800 c.p.b. did not protect naive baboons, nor did it significantly reduce challenge worm recovery from baboons with a 13-week-old, 500 c.p.b. S. mansoni primary infection. Obvious pathology was seen at the site of vaccination in the first but not the second BCG experiment. These results partly support the findings in mice that non-specific macrophage and monocyte activators give partial protection against schistosome infections but they also illustrate that rodents and primates do not necessarily react identically. Hence, findings from rodent models should be extrapolated to man with some caution.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1984

Immunity after treatment of human schistosomiasis mansoni. I. Study design, pretreatment observations and the results of treatment.

This paper describes the design of a study on immunity to reinfection after treatment of children with Schistosoma mansoni infections, the initial observations on transmission that led to the selection of the study population, the effects of treatment, and the results of immunological tests carried out before and at five weeks after treatment. Iietune village in Machakos District, Kenya, was selected on the basis of high prevalence and intensities of infection in a small preliminary survey, a stable population living in a small area amenable to detailed study, and a lack of previous intervention in the area. Subsequent observations over a pretreatment period of one year confirmed that prevalence and intensities of infection among children attending the local primary school were high. This was associated with extensive contact of members of the community with water-bodies shown to contain large numbers of infected snails. Analysis of pretreatment intensities of infection and water contact patterns in the schoolchildren allowed the selection of 129 children showing a broad scatter between: (a) high intensity, low water contact, and predicted to be non-immune, and (b) low intensity, high water contact, and predicted to be immune. These children were treated with oxamniquine, 30 mg/kg in divided doses. Five weeks after treatment, 70% of children showed apparent complete cure, and the over-all reduction in geometric mean egg output was 98.9%. Since these children represented only a small proportion of the whole community, there was no obvious reduction in transmission, as reflected by snail infection rates, during the following five-month period. Thus, we are in a position to determine whether successfully treated children do or do not become reinfected in a high transmission environment in which it will be possible to make direct estimates of exposure. Immunological tests carried out immediately before treatment were consistent with a pattern of high exposure leading to the early expression of immune responses in most infected children. Eosinophil levels were elevated in 61% of the children, all of whom showed detectable levels of antibodies against adult worm and egg antigens, as measured by ELISA. In addition, all patients showed antibodies capable of mediating eosinophil-dependent killing of schistosomula. At five weeks after treatment, eosinophil counts and anti-adult worm antibody levels had risen, whereas anti-egg antibodies remained grossly unchanged. The wide variation in the levels of responses shown by different individuals will allow us to test whether such responses are associated with resistance to reinfection during the follow-up period.

Adolescent↗
PubMed1984

Experimental Schistosoma mansoni infection in vervet monkeys (Cercopithecus aethiops) in Kenya: I. Susceptibility to a primary infection.

Groups of five 3-kg Kenyan monkeys, Cercopithecus aethiops, were exposed individually to 150,600 or 1500 Schistosoma mansoni cercariae per monkey. Three monkeys died soon after the infections became patent and the survivors were autopsied 4 months after exposure. Mortality and most haematological, parasitological and pathological sequelae of infection were dose-related, but not the white cell response or changes in the levels of serum proteins or fibrinogen. No gross liver fibrosis was seen. Comparison of this study with earlier ones on related cercopithecine monkeys suggests that the vervet closely resembles the baboon in its response to S. mansoni infections. Difficulties in managing and maintaining vervets can be overcome by using colony-bred or properly adapted feral animals. Thus, the vervet provides a cheaper, more readily available primate model for experimental S. mansoni studies. A prolonged infection, sufficiently heavy to permit reliable parasitological monitoring without undue mortality, should be provided by 150 S. mansoni cercariae per kg body-weight, using the Kenyan strains of vervet and parasite.

Animals↗
PubMed1984

Observations on the ability of repeated, light exposures to Schistosoma mansoni cercariae to induce resistance to reinfection in Kenyan baboons (Papio anubis).

Using groups of 4 baboons (Papio anubis), 21.0% of a trickle exposure of 480 Schistosoma mansoni cercariae/baboon (10/week for 48 weeks) were recovered as adult worms (Group A) compared with 72.6% from a single massive exposure of 2500 cercariae/baboon (Group C). Group B, exposed first to the trickle and then to the massive exposure simultaneously with Groups A and C, yielded a worm recovery of 54% which was slightly but significantly less than Group C. The trickle infection apparently induced a substantial resistance to light re-exposure but only a partial, although significant, resistance to a massive re-exposure. In Group B, however, there was a marked reduction in the degree of gross pathology, despite high tissue egg production by the mature challenge worms. The parasitological results, in terms of resistance to reinfection by and development of pathology to a trickle infection, are not materially different from those obtained in studies using conventional heavy primary and challenge exposures with S. mansoni. The significance of these findings is discussed in relation to the epidemiology of human schistosomiasis mansoni in which heavy exposures are believed to be the exception rather than the rule.

Animals↗
PubMed1983

Observations on possible immunity to reinfection among Kenyan schoolchildren after treatment for Schistosoma mansoni.

In February 1977, 306 out of 409 six- to 16-year-old Kenyan schoolchildren were found to be infected with Schistosoma mansoni. Prevalence and intensity were directly related to age and indirectly to the distance between the child's home and the transmission site, but were not related to the child's sex. Most children were treated with hycanthone in July 1977. Pretreatment blood samples were taken from 100 study children for eosinophil counts and measurements of cytotoxic anti-schistosomular antibody levels. Blood and faecal samples were re-examined five times between November 1977 and July 1979. Whole school resurveys in July 1978 and 1979 confirmed the continuation of transmission after chemotherapy. 'Reinfection' rates in the study children, incorporating both failed treatment and true reinfections, were significantly reduced in children, with both detectable antibody and eosinophil counts above 400/mm3, compared with children with neither. Children with either detectable antibodies or high eosinophil counts (mainly the latter) had intermediate reinfection rates. Neither sex, age nor pretreatment intensities influenced reinfection rates, but location of dwelling did: children from distant homes had lower rates. However, the effects of residence and 'protection' were not directly linked. The implication of these results, namely that infection can confer immune protection to reinfection after treatment, is being explored in further studies.

Adolescent↗