Biomedical subjects

R F Sturrock

Publications and source records attributed to R F Sturrock.

At least 37 records · Page 2Linked to original sources

PubMed1994

A survey of Schistosoma mansoni induced kidney disease in children in an endemic area of Machakos District, Kenya.

The association between Schistosoma mansoni infection and kidney lesions was investigated in school children selected from three primary schools in Machakos District, Kenya, namely Miu (n = 159), Kitengei (n = 160) and Misuuni (n = 99) schools. The children were examined parasitologically for S. mansoni infection, clinically for enlargement of the liver and spleen, and biochemically for proteinuria and serum and urine creatinine. High prevalences of S. mansoni infection, ranging from 84-96%, were seen in all the schools, but the geometric mean intensity of egg excretion varied, being relatively low in Misuuni (31 eggs/g), medium in Miu (182 eggs/g) and high in Kitengei (413 eggs/g). The prevalence of pathological proteinuria (> or = 200 mg/l) in the schools ranged from 10.1% in Miu to 28.8% in Kitengei. No difference in the levels of proteinuria was noted between age or sex groups. No association between intensity of infection and pathological proteinuria was observed in any of the schools, nor was any correlation between organomegaly and proteinuria observed. However, significant correlations between malaria and organomegaly (p < 0.001) and between malaria and proteinuria (p < 0.05) were observed when pooling data from all schools. These findings suggest that S. mansoni induced nephrotic syndromes are not common in children from this highly endemic area of Kenya.

Adolescent↗

PubMed1994

Observations on the effects of different chemotherapy strategies on the transmission of Schistosoma mansoni in Machakos District, Kenya, measured by long-term snail sampling and cercariometry.

Transmission of Schistosoma mansoni was monitored by routine snail sampling for Biomphalaria pfeifferi and by supplementary cercariometric measurements in 4 neighbouring study areas in Machakos District, Kenya. After 1 year, extensive, population-based chemotherapy with a single dose of praziquantel was given in 3 areas, but only minimal treatment in the fourth. In the year preceding treatment, seasonal transmission of S. mansoni and other non-human trematodes occurred in all 4 areas, despite some ecological differences and the effects of earlier treatment campaigns in 1 of the study areas. After treatment of all infected subjects in one area in which there had been earlier chemotherapy campaigns, S. mansoni transmission remained very low. It was reduced for at least 2 years after chemotherapy targeted at either all heavily infected subjects or all infected school children, but it was unaffected in an area where treatment was restricted to those few very heavily infected cases at risk of developing disease. Nowhere was transmission entirely eliminated by chemotherapy and that of non-human trematodes continued unabated. The snail data correspond well with the human, parasitological data. Targeting school children was as effective as more extensive campaigns, but chemotherapy alone never stopped S. mansoni transmission: reinfection was inevitable, at rates determined by ecological factors affecting snail populations.

Animals↗

PubMed1994

Epidemiology, immunology and chemotherapy of Schistosoma mansoni infections in a recently exposed community in Senegal.

Schistosoma mansoni was introduced in the Richard Toll area (Senegal) around 1988, probably due to man-made ecological changes in the Senegal river basin. Since 1991, we investigate the community of Ndombo, close to Richard Toll. Four random population samples of approximately 400 subjects are surveyed, starting at 8 months intervals. Each cohort is examined parasitologically (Kato-Katz), clinically, serologically (circulating antigen and antibody profiles); treated with praziquantel 40 mg/kg; and followed up 6-12 weeks, 1 and 2 years after treatment. Water contact patterns and snail densities are longitudinally surveyed. In the first cohort, prevalence of infection was 91%, with 41% excreting over 1000 eggs per gram (epg); the mean egg count was 646 epg, individual counts up to 24,000 epg. Prevalences remained almost 100%, but egg counts declined strongly in adults, in spite of continued exposure and the supposed lack of acquired immunity. Antigen detection in serum and urine confirmed that the egg counts genuinely reflect variations of worm burdens. Serum circulating anodic antigen (CAA) provided intriguing epidemiological information on worm burdens, while circulating cathodic antigen (CCA) showed promise for non-invasive diagnosis and screening. So far, similar epidemiological results were found in subsequent cohorts, although some variations were observed, possibly due to seasonal transmission fluctuations. IgE levels increased with age, while IgG4 peaked in the age-group 10-19 years. IgE and IgG4-levels against adult worm antigen (AWA) and soluble egg antigen (SEA) increased between cohort 1 and cohort 3 in almost all age-groups. In all 3 cohorts examined so far a strong correlation between IgG4 and pre-treatment egg-load was observed. Further follow-up and analysis, and comparison with chronically infected populations will provide insight in the development of acquired immunity. Abdominal discomfort was reported by 61% and diarrhoea by 33% of the subjects in the first cohort; mild hepatomegaly was found in 16%, splenomegaly in 0.5%. There was no correlation between frequency of symptoms and egg counts. This low morbidity, in spite of intense infections, was confirmed by ultrasound, and may be due to the recent nature of the focus. In the first cohort, 82% of treated subjects still excreted eggs 12 weeks after treatment, though egg counts declined strongly. Antigen detection confirmed these results. Parasitological negativation rates in subsequent cohorts, followed up sooner after treatment, improved but remained remarkably low. The low drug efficacy may be due to very rapid reinfection (though further reinfection after one year was limited), and/or to the lack of immunity in the population. Reduced susceptibility of the local schistosome strain can not be excluded, however. Praziquantel treatment provoked impressive but transient side effects (colics, vomiting, urticaria, oedema), the frequency of which correlated with intensity of infection.

Adolescent↗

PubMed1993

Immunity after treatment of human schistosomiasis: association between cellular responses and resistance to reinfection.

Previous studies have demonstrated the development of an age-dependent resistance to reinfection after chemotherapeutic cure of the helminthic parasite Schistosoma mansoni. Here we report on a longitudinal investigation of cell-mediated responses in infected individuals before and after treatment which was designed to outline those parameters important in mediating a protective response. A well-defined study group of 89 individuals with an age range of 9 to 35 years was selected from an area of high S. mansoni transmission in the Machakos district of Kenya. Peripheral blood mononuclear cell proliferation and cytokine production (interleukin-2 [IL-2], gamma interferon IL-5, IL-4, and tumor necrosis factor) in response to different crude life cycle-stage antigens of S. mansoni were assessed longitudinally in vitro before, 3 months after, and 1 year after treatment. Detailed statistical analyses of the results from this study have indicated a clear negative association between the proliferative responses to adult- and schistosomulum-stage antigens and subsequent reinfection intensity in older individuals (14 to 35 years) which was not present in the younger individuals (9 to 13 years). This association was significant even after the effects of age, sex, and exposure had been accounted for in multiple regression analyses. Cytokines were detected predominantly in response to adult worm and egg antigen extracts. An inverse association between the two cytokines gamma interferon and IL-5 was detected in response to all antigens at the three time points investigated, indicating cross-regulation in the production of these two mediators. Differences in antigen-specific cytokine levels between the two age groups were detected, with significantly higher IL-5 levels detected in the older (more resistant) age group. An inverse correlation between this cytokine and reinfection was detected but could not be dissociated from the effects of age and exposure in multiple regression analysis.

Adolescent↗

PubMed1993

Epidemiology of Schistosoma mansoni infection in a recently exposed community in northern Senegal.

The epidemiology of Schistosoma mansoni infection was investigated in Ndombo, a village in the epicenter of a very recent outbreak of schistosomiasis in northern Senegal. Repeated fecal egg counts and antigen detection in urine and serum were carried out in a random population sample (n = 422). Eggs were found in 91% of the subjects, with 41% excreting > 1,000 eggs per gram of feces (epg) (mean egg load of 646 epg). The prevalence was almost 100% in groups greater than five years of age. In spite of the supposed absence of acquired immunity, intensities of infection decreased strongly in adults. Antigen detection confirmed the high prevalence and intensity of infection and the age-related distribution of worm loads. The emergence of this new focus is probably due to the ecologic impact of newly built dams and the extension of irrigation projects in the Senegal basin.

Adolescent↗

PubMed1992

Immunity after treatment of human schistosomiasis: association between IgE antibodies to adult worm antigens and resistance to reinfection.

Previous studies in school children have demonstrated the slow development with age of resistance to reinfection after chemotherapy of Schistosoma mansoni infections, and have indicated that inappropriate ("blocking") antibody responses prevent the expression of immunity in young children. The present study was designed to investigate further the nature of the protective responses, by serological studies on a group of 151 S. mansoni-infected individuals resident in an endemic area in Machakos District, Kenya. Antibody levels against various antigens in blood samples before treatment were related to intensity of previous infections; antibodies in blood samples taken 6 months after treatment were related to cumulative reinfection rates over the following 30 months. IgE against an adult-worm antigen preparation correlated positively with age and negatively with reinfection. In contrast, IgE antibodies against other life-cycle stages showed either no relationship or the reverse correlation. Furthermore, antibodies of other isotypes against adult-worm antigens showed no correlations with reinfection. The correlation with IgE could be demonstrated for different preparations of adult worms, including a periodate-treated preparation presumptively depleted of carbohydrate epitopes. For both the intact and the periodate-treated preparations, multiple regression analysis of the results for children less than or equal to 16 years old demonstrated an IgE effect after allowing for age, although this effect was not observed in a previously studied group of school children. Western blot analysis of the adult-worm preparation revealed a limited set of antigens recognized by IgE, among which an antigen of 22 kDa was prominent. The qualitative presence of IgE against this antigen could also be shown to be related to a lack of subsequent reinfection.

Adolescent↗

PubMed1992

On the use of age-intensity data to detect immunity to parasitic infections, with special reference to Schistosoma mansoni in Kenya.

We consider two phenomena, related to the host age-intensity profiles of parasitic infections, which have been suggested to be indicative of acquired immunity: (i) a lower age of peak intensity among more intensely infected hosts; and (ii) a decline with age in the dispersion of the distribution of parasites between hosts. We demonstrate that these phenomena occur among Kenyan schoolchildren infected with Schistosoma mansoni, although the magnitude of both is small. We also examine the mathematical models underlying these predictions and conclude that both phenomena are possible in the absence of acquired immunity or, indeed, in the absence of any density-dependent effect. In our opinion, insufficient attention has been focused upon mathematical models, describing the null hypothesis, i.e. density-independent models. In particular, we regard the usual assumptions made for the two stochastic components of these models, describing the heterogeneity between hosts and the probabilistic nature of infection and death of parasites, as too rigid and unrealistic. We demonstrate that deviation from these assumptions undermines the qualitative distinctions between models which describe acquired immunity or density dependence and those which are density-independent.

Adolescent↗

PubMed1992

Harmonization of research and control in schistosomiasis.

I have been employed by several different organizations during over 30 years working on schistosomiasis, the majority spent in endemic areas of the Caribbean, South America, Africa and the Western Pacific. Much of the work is best classified as applied research but sometimes it strayed to the extremes of either public health control programmes or pure research. Over this period, there have been several significant research developments that have altered our whole approach to control. Ideally, research and control should complement each other but, in reality, they sometimes have conflicting objectives. Public health workers understandably wish to provide immediate, short-term protection to the communities in their care, but research workers may, within ethical limits, reasonably want to observe untreated communities for extended periods in order to understand the underlying processes of transmission, disease pathogenesis and immunity to help develop more effective control measures. An example of this situation has occurred recently in Senegal where water development projects seem to have favoured the introduction and spread of Schistosoma mansoni in the Senegal River Basin. I have been asked to be the scientific consultant to the newly formed ESPOIR programme, linking European research organizations and the Senegal Ministry of Health, to reconcile the conflicting aims of public health workers, wishing to use whatever funds can be obtained for an immediate chemotherapy to try to eliminate the focus, at present confined to the vicinity of a relatively small, commercially run sugar irrigation scheme; and research workers who see a rare chance to study the development of immune mechanisms in a adults in a community not previously exposed to the infection.(ABSTRACT TRUNCATED AT 250 WORDS)

Africa↗

PubMed1992

Human IgE responses to Schistosoma mansoni and resistance to reinfection.

Schistosoma mansoni infected Kenyan patients were treated and the intensities of their reinfections were followed over the next two years. In addition, their pre- and six month post-treatment serum levels of IgG1-4, IgM, and IgE, specific for schistosomula, egg and adult worm, were measured in ELISA. No reinfection took place before six months post-treatment. Reinfection intensities varied with age; the younger children becoming reinfected at significantly higher intensities than older individuals. When antibody and reinfection levels were compared, only the six month post-treatment IgE response against adult worm correlated negatively with intensities of reinfection and, therefore, was predictive of resistance or immunity to reinfection. IgE and IgG specific Western Blots were carried out. The adult worm antigens recognized by IgE were restricted compared with the IgG responses of the same patients, although no individual antigen was uniquely recognized by the IgE isotype. A dominant 22 kDa antigen was recognized by most but not all high IgE responders. Patients with IgE responses against this antigen suffered significantly lower subsequent levels of reinfection, compared with non-responders. A monospecific rabbit antiserum against the 22 kDa adult worm antigen showed that this antigen is specifically located in the tegument of the adult worm and of 'lung' and 'liver' stage schistosomula, but is absent from the early 'skin' schistosomula. It is possible that this antigen is a target for human IgE mediated immune effector mechanisms active against the post skin stage schistosomula and that this is boosted by the death of adult worms.

Adult↗

PubMed1992

Identification of schistosome-infected snails by detecting schistosomal antigens and DNA sequences.

Cercarial shedding tests do not provide species identification of the schistosomes concerned and cannot detect prepatent schistosomal infections. We have demonstrated that both immunodetection by ELISA of schistosomal antigens in snail hemolymph, and dot hybridization of snail extracts by a DNA probe representing highly repeated sequences, proved suitable for detecting infected snails during prepatency as well as patency. A group-specific monoclonal antibody was found to be suitable for detecting Schistosoma mansoni infection in Biomphalaria sp., but not for positive identification of S. haematobium in Bulinus sp. Comparative evaluation of the diagnostic qualities, and technical aspects and cost of these tests, point to the superiority of the immunodetection approach for large scale detection of snails prepatently infected with S. mansoni. This approach is potentially useful for providing extended information on schistosome-snail epidemiology that may facilitate rapid evaluation of the danger of post-control reinfection, and help make decisions on the time and place of supplementary control measures. In this context the potential usefulness of the immunodetection or DNA probing approach for facilitating catalytic model representation of schistosome-snail epidemiology warrants further evaluation. Specific identification of S. haematobium in Bulinus by either of these approaches may be possible depending on the development of suitable antibodies or DNA probes.

Animals↗

PubMed1992

Human immunity to Schistosoma mansoni: observations on mechanisms, and implications for control.

This review summarizes the personal experiences of the authors and their colleagues during ten years of field and laboratory studies on human immunity to Schistosoma mansoni infections. There is evidence for the very slow development with age of an acquired resistance to reinfection (demonstrable after chemotherapy of the primary infection) distinguishable from a lack of reinfection due to reduced exposure. The implications of this immunity for the design of chemotherapy programs targeted at infected schoolchildren are discussed. Observational studies on the mechanisms of immunity have demonstrated a marked helminthocidal capacity of eosinophils. Subsequent correlative studies have indicated a role of IgM and IgG2 "blocking" antibodies in maintaining the continued susceptibility of young children, and of IgE antibodies in mediating protection in older individuals. Some problems in studying human immunity, and the implications for vaccine development, are also discussed.

Animals↗

PubMed1991

Comparison of different chemotherapy strategies against Schistosoma mansoni in Machakos District, Kenya: effects on human infection and morbidity.

A comparison was made of the long-term impact of different methods of administration of chemotherapy (oxamniquine, 30 mg/kg in divided doses; or praziquantel, 40 mg/kg) on prevalence and intensity of Schistosoma mansoni infection in four areas in Kangundo Location, Machakos District, Kenya. In Area A, treatment was offered in October 1983 and again in April 1985 to all infected individuals. In Area H, treatment was offered in April 1985 to individuals excreting greater than or equal to 100 eggs per gram (epg) of faeces. In Area S, treatment was offered in April 1985 to all infected school children, within the framework of the primary schools. In the witness area, Area W, treatment was given in April 1985, for ethical reasons, to a small number of individuals excreting greater than or equal to 800 epg. Prevalence and intensities of infection were subsequently monitored at yearly intervals for three complete post-treatment years. In the Area S schools, clinical examination was also carried out at yearly intervals. Treatment of all infected individuals on two occasions (Area A) was the most effective and long-lasting way of reducing prevalence and intensity of infection. In this area, however, some earlier interventions had been carried out and pre-treatment intensities were lower than in the other areas. Treatment only of infected schoolchildren (Area S) also had a marked and prolonged effect, comparable to or better than treatment of individuals with heavy infections (Area H). Treatment of infected schoolchildren also caused a persistent reduction in the prevalence of hepatomegaly, and there was suggestive evidence from intensities of infection in community stool surveys (but not from incidence rates) of an effect on transmission. In all study areas, reinfection was most rapid and most intense among children. These findings are discussed in the light of theoretical considerations and of results from other studies, both on schistosomiasis and on intestinal helminths. We conclude that, in areas of low morbidity such as Kangundo, chemotherapy of schoolchildren only, at intervals of up to 3 years, is a satisfactory way of producing a long-term reduction in both intensity of infection and morbidity.

Adolescent↗

PubMed1991

Immunization of mice and baboons with the recombinant Sm28GST affects both worm viability and fecundity after experimental infection with Schistosoma mansoni.

A member of the glutathione S-transferase family, Sm28GST has previously demonstrated a good ability to protect rodents against experimental infection with Schistosoma mansoni. In order to evaluate its efficacy in a model closer to man, two different protocols of immunization with recombinant Sm28GST were tested on baboons in a large-scale trial. Three injections in the presence of aluminium hydroxide as adjuvant resulted in a significant 38% reduction in the adult worm burden together with a trend for a lower percentage of inflammatory tissue in the liver. Individual levels of protection, ranging from 0 to 80%, underlined the heterogeneity of the immune response to this purified molecule in outbred primates. On the other hand, two injections of Sm28GST in the presence of aluminium hydroxide and Bordetella pertussis reduced female schistosome fecundity by 33%, with a more pronounced effect (66%) on faecal egg output; there was also a trend, in this protocol, for decrease of the mean granuloma surface in the liver. Individual anti-Sm28GST IgG antibodies were apparently unrelated to levels of immunity, but there was partial evidence that cytophilic IgE might play a role in the immune mechanisms affecting worm viability, but not fecundity. In the mouse model, Sm28GST vaccination resulted in a lower hatching ability of tissue eggs recovered from immunized mice whereas passive transfer of specific anti-Sm28GST T-lymphocytes, one day before infection, significantly reduced the number of eggs in the liver of mice. We propose that different protocols of immunization with a recombinant molecule can impede Schistosoma mansoni worm viability and fecundity, but can also affect miracidium physiology, with important consequences for disease transmission and granuloma-derived pathology.

Animals↗

PubMed1989

A comparative evaluation of snail sampling and cercariometry to detect Schistosoma mansoni transmission in a large-scale, longitudinal field-study in Machakos, Kenya.

In an operational Schistosoma mansoni field-study in an area about 20 km 2 (population approximately 8000), transmission detection by simple snail sampling was compared with cercariometry. Between 1985 and 1987, 62 field sites were sampled at fortnightly intervals. Of a total of 2758 field observations, 89.8% gave full snail data; 64.4% full cercarial data; and 61.7% complete data for both methods. The complete data sets showed significant but not strong correlations between Biomphalaria pfeifferi (total and infected with S. mansoni or other trematodes) and cercarial (S. mansoni and non-human) recoveries. Non-human (but not S. mansoni) cercarial recovery decreased with deteriorating cercariometry filter quality. Both snail and cercarial recoveries diminished significantly with increasing water flows at the time of collection. Many samples yielded infected snails or cercariae, but not both, and neither method detected significantly more transmission sites. The method of choice for detecting transmission in a large-scale field-study depends on logistical and financial considerations. Relatively simple snail sampling allows quick, cheap and widespread data collection adequate for most purposes but more complicated cercariometry is still valuable for specific, small-scale studies.

Animals↗

PubMed1989

The control of schistosomiasis: epidemiological aspects of reinfection.

Current strategies for schistosomiasis control rely heavily on drug treatment intended to reduce morbidity and disease to an insignificant level of public health importance. This approach reduces but rarely, if ever, eliminates transmission. Indeed, snail infection rates may be little altered by such chemotherapy. Reinfection is inevitable. The mean human community prevalence usually returns rapidly to precontrol levels but the mean intensity of infection takes much longer, distorting the general relationship between the two. Because of the focality of schistosomiasis transmission, retreatment based on mean population prevalence is often too late to protect people living near active transmission sites. However, if suitable methods can be developed to examine man after treatment, they should simplify the detection of the main transmission sites, allowing the employment of alternative, focal control measures to consolidate the beneficial effects of mass chemotherapy.

Animals↗

PubMed1989

Pathology resulting from the administration of a live attenuated anti-Schistosoma haematobium vaccine in baboons.

Baboons (Papio anubis) were injected in the leg muscle with 18,000 20 Krad irradiated schistosomula of Schistosoma haematobium. Four protocols were followed: single, primary injection; single injection into animals primed by patent S. haematobium infection; secondary vaccine injection following an earlier injection; and single injection following praziquantel treatment of infected animals. Injection of the putative vaccine elicited localized mixed inflammatory infiltration at the site of injection which was both intense and prolonged. Three grades of tissue reaction were seen: the relatively mild primary response; the response in infected animals which had enhanced tissue eosinophilia; and the response in animals primed by prior injection and drug-treated prior infection. The latter 2 showed intensification of eosinophilia, stellate abscesses in the lesion centers, and perischistosomular Hoeppli precipitates. Intramuscular lesions peaked at 14 days for the primary response and at 7 days for all secondary responses. Traces of the milder lesions persisted beyond 4 weeks; more severe reactions healed more rapidly. Some schistosomula survived for 14 days in the milder reactions. A few larvae were deposited in the skin by backflushing of the injectate which produced local inflammation. Compared to mice, live schistosome vaccines injected into baboons elicited greater local inflammation; however, while evidence suggested that sporadic vaccine schistosomula did reach the lymphatic nodes draining the injection sites, no systemic lesions were found and the injection sites healed in approximately 5-6 weeks without permanent damage.

Animals↗

PubMed1989

Identification of snails infected with schistosomes by ELISA employing monoclonal antibodies: Schistosoma mansoni in laboratory snails (Biomphalaria glabrata) and in field snails (Biomphalaria pfeifferi) from Kenya.

An enzyme-linked immunosorbent assay (ELISA) employing monoclonal antibodies was used for detecting Schistosoma mansoni antigens in hemolymph of laboratory snails (Biomphalaria glabrata) in Kenya. Infected laboratory snails shedding cercariae were differentially identified by ELISA from uninfected snails with 100% sensitivity and specificity. Prepatent infections were detected by ELISA from 2 weeks after exposure to miracidia. Thus, ELISA revealed infection 3 weeks before maximal patency was reached (5-6 weeks post-exposure). Infected field snails (B. pfeifferi) shedding cercariae were differentially identified by ELISA, with 100% sensitivity and specificity, from uninfected field snails and from snails naturally infected with other trematodes (echinostomes and strigeids). Prepatent infections with S. mansoni were readily identified by ELISA in field snails. A case is demonstrated where infection rate, as determined by shedding test alone, was 9.8%, whereas the combined figure of prepatent and patent infection rates was 22.9%

Animals↗

PubMed1989

Effects of borehole wells on water utilization in Schistosoma haematobium endemic communities in Coast Province, Kenya.

To determine the impact of the introduction of borehole wells on water use patterns and the consequent risk of transmission of Schistosoma haematobium in 3 endemic villages in Kenya, we performed a survey (a 1:6 sample of affected households) to identify sources of water and types of water utilization before and after well introduction. Water usage was also determined in 2 unaffected neighboring villages not given borehole wells, but having continuous access to piped water from communal taps. Prior to borehole well construction, significantly more high-risk water use occurred in the borehole villages vs. comparison villages in terms of water gathered for cooking, drinking, dish washing, and bathing; residents of both types of villages preferred high-risk sources (marshes and ponds) for clothes washing. Following well introduction, there were significant declines in the use of high-risk water for drinking, cooking, and dish washing, but not for bathing or clothes washing. A higher proportion of individuals from the 3 borehole villages reported some type of continued contact with high-risk water sources. Despite well introduction and a 3 year chemotherapy program among school-aged children, a 21-28% incidence of infection persisted among children in the villages, suggesting minimal impact on transmission. Regular monitoring for S. haematobium infected snail sites showed no decline in the number or proportion of infected snails. Borehole well introduction can significantly alter some forms of water usage, but social and water quality factors may limit the ability of communal wells to reduce S. haematobium transmission.

Adult↗