Biomedical subjects

R F Sturrock

Publications and source records attributed to R F Sturrock.

At least 19 recordsLinked to original sources

PubMed2003

The detection of antibodies against Schistosoma mansoni soluble egg antigens (SEA) and CEF6 in ELISA, before and after chemotherapy.

Circulating IgG antibody reactivity and excreted egg counts were investigated in 489 Kenyans given chemotherapy for schistosomiasis mansoni. Antibody reactivity was measured in ELISA, using either unfractionated aqueous soluble constituents of Schistosoma mansoni eggs (SEA) or CEF6 (a soluble fraction of S. mansoni eggs containing two cationic antigens) as the antigen source. Antibody reactivity for each antigen source was strongly associated with egg counts, both pre- and post-treatment. Approximately 6 months after chemotherapy, egg counts were zero in 84% of the subjects. The mean optical densities (OD) measured in the post-treatment ELISA were 60% (CEF6) or 45% (SEA) lower than the pre-treatment values, the reduction in the OD with CEF6 as antigen source being significantly greater than that observed with SEA (P <0.001). The usefulness of an assay for antibody reactivity in monitoring the effects of the treatment of schistosomiasis is discussed.

Adolescent↗

PubMed2001

Seasonality in the transmission of schistosomiasis and in populations of its snail intermediate hosts in and around a sugar irrigation scheme at Richard Toll, Senegal.

Irrigation for intensive sugar cultivation started in the early 1980s at Richard Toll, some 100 km from the mouth of the Senegal River. Infections with Schistosoma mansoni were first seen in late 1988. This study records quantitative snail surveys for over 3 years from 1992 at sites representing different habitats in and around the irrigation scheme. Populations of both Biomphalaria pfeifferi (the intermediate host of S. mansoni) and Bulinus spp. (mainly B. truncatus, the local host of S. boris) peaked in late 'spring' or early 'summer', depending on the habitat, and then remained low until the following spring', B. pfeifferi favoured smaller, man-made habitats with most transmission between May and August each year. The less abundant Bulinus spp. favoured larger natural and man-made habitats with most S. bovis transmission between April and July. S. mansoni infections were more, but S. bovis infections were less abundant than other trematodes in their respective snail hosts. Ecological changes in the early 1980s due to sugar irrigation pre-dated similar, more widespread changes in the late 1980s when the completion of dams across the Senegal River prevented seasonal rain fed floods and sea water intrusion. S. mansoni has since spread rapidly around Richard Toll. The incompatibility of the local S. haematobium strains with the dominant bulinid snails has so far prevented an epidemic of urinary schistosomiasis at Richard Toll, but the invasion of similar downstream habitats by susceptible B. globosus is worrying. The principal control measure, chemotherapy, given in the 'winter' would minimise the rate of reinfection. It could be reinforced by judicious mollusciciding within the sugar irrigation scheme but not elsewhere.

Animals↗

PubMed2001

Schistosomiasis epidemiology and control: how did we get here and where should we go?

Although a disease of great antiquity, scientific studies of schistosomiasis began only 150 years ago. The complete life-cycle was not described until just before the First World War, making it possible at last to plan proper community control programmes. Inadequate tools prevented their effective implementation until well after the Second World War when new tools became available, thanks to the newly formed World Health Organization. Molluscicides spearheaded control programmes until the late 1970s but were then replaced by the newly developed, safe drugs still used today. Whatever the method used, the initial goal of eradication was, in the light of experience and cost, gradually replaced by less ambitious targets; first to stop transmission and then to reduce morbidity. The most successful programmes combined several methods to minimise reinfection after chemotherapy. Comparisons between different programmes are difficult without using appropriate, standardised diagnostic techniques and the correct epidemiological measurements. Some examples will be presented, mainly from our studies on Schistosoma mansoni in Kenya. Drug resistance on a scale comparable with malaria has not occurred in schistosomiasis but the likely withdrawal of all drugs except praziquantel leaves its control extremely vulnerable to this potential problem. An effective, affordable vaccine for use in endemic countries is unlikely to be ready for at least 5 years, and developing strategies for its use could take a further decade or more, judging from experience with drugs and molluscicides. In the interim, by analogy with malaria, the most cost-effective approach would the use of drugs combined with other methods to stop transmission, including molluscicides. The cost of molluscicides needs to be reduced and fears allayed about their supposedly adverse ecological effects.

Adolescent↗

PubMed1999

Cellular immune responses of a Senegalese community recently exposed to Schistosoma mansoni: correlations of infection level with age and inflammatory cytokine production by soluble egg antigen-specific cells.

A recently reported epidemic of Schistosoma mansoni infection in Senegal provided an opportunity to study the dynamics of the development of immunity to human schistosomiasis. We report here on the cell-mediated immune response in a population of 99 females and 95 males, with particular emphasis on the relationship between intensity of infection and age. We found that the intensity of infection correlated negatively with age in females but not in males. In men and women, both Th1- and Th2-type cytokines were detected upon in vitro stimulation of PBMCs with soluble egg antigen (SEA) or soluble adult worm antigens (SWAP). In the female group, SEA-induced PBMC proliferation was associated with the production of IFN-gamma, IL-2 and IL-5, all of which correlated negatively with intensity of infection. Most cytokine production correlated positively with age. Spontaneous production of TNF-alpha, IL-6 and IL-10 was higher in the infected population than in an uninfected control group. Our results suggest that immunity to infection could be more pronounced in the female population and associated with a Th0/1 + 2 pattern of cytokine secretion mediated by soluble egg antigen (SEA).

Adolescent↗

PubMed1998

The development of schistosomiasis mansoni in an immunologically naive immigrant population in Masongaleni, Kenya.

The relocation of several thousand members of the Kamba tribe from the Kyulu Hills to the Thange valley near Masongaleni in Kenya provides an excellent opportunity to study the development of the immune response to schistosomiasis mansoni in a population with little or no previous experience of the infection. An adjacent, well-established Kamba community with similar patterns of water contact provides a suitable endemic control population. The immigrants were, uniquely, examined shortly after their arrival in the endemic area, while the prevalence of infection was still low. At this time faecal egg counts peaked atypically around 30 years of age. Over the next 12-18 months infection increased rapidly, especially among teenagers, producing a pattern of infection more typical of endemic communities. This substantially narrows estimates of the time required to develop the important determinants of the age-intensity profile, supporting the notion that changes related to age per se, rather than duration of infection, dominate. Age-dependent factors might include behaviour or physiology, including immune response. This paper provides the background for continuing longitudinal studies on the development of immunological responses to this parasite.

Adolescent↗

PubMed1997

Schistosoma mansoni: maturation rate and drug susceptibility of different geographic isolates.

The fecundities and drug susceptibilities of Schistosoma mansoni isolates from Senegal, Puerto Rico, and Kenya have been examined in mice. The Senegal parasite, obtained from the field in 1993, was shown to have a longer prepatent period (eggs first recovered in the faeces on Day 46 after infection) than those of two isolates, from Puerto Rico and Kenya, that had been maintained for a long period in the laboratory (faecal eggs recovered on Days 38 and 36 after infection, respectively). A Kenyan isolate, also collected from the field in 1994, was shown to mature more slowly than the laboratory-maintained Kenyan isolate. Tissue egg counts confirmed that early in infection the fecundity of the recently collected isolates from Senegal and Kenya was significantly lower than that of the long-term laboratory-maintained Kenyan isolate. Praziquantel and oxamniquine treatment of 8-week-old infections caused a significant (P < 0.001) reduction in worm burden in all isolates tested. However, the reduction in worm burden after praziquantel treatment of infections of the Senegal isolate (50% reduction) was significantly lower than the > 90% reductions in worm burdens after praziquantel treatment of mice infected with either of the Kenyan isolates (P < 0.001). The study confirms that despite being tolerant to praziquantel, the Senegal isolate is fully susceptible to oxamniquine. The praziquantel tolerance of the Senegal parasite is not solely attributed to the state of maturation of the parasite at the time of drug administration.

Animals↗

PubMed1997

Spatial patterns of human water contact and Schistosoma mansoni transmission and infection in four rural areas in Machakos District, Kenya.

This paper presents the results of microgeographical studies of human water contact behavior and Schistosoma mansoni transmission levels and intensity of infection in four rural areas in Machakos District, Kenya. The relationship between intensity of infection (geometric mean egg counts) in 3502 persons aggregated in 120 household clusters and eight independent variables was investigated using straight and stepwise linear regression and mapping techniques. Results indicate that the two water contact variables, mean frequency per person and mean duration per person, as well as mean number of sites used per person, a transmission index and mean distance to the most frequently used site were the strongest predictors of geometric mean egg counts. All three distance variables were usually negatively associated with infection although intensity of infection and water contact declined relatively slowly with distance from the streams. This pattern appears to be owing to a combination of the relatively short distances, a general lack of safe alternative water sources and the use of more distant water contact sites both inside and outside the study area during periods of drought. The study of snail-to-man transmission identified number of infected snails as the major transmission variable and number of contacts as the major predictor variable. Mapping of total egg counts at the household cluster level and total number of infected snails revealed spatial association with transmission sites. All results varied considerably between study areas, owing to differences in exposure levels, transmission patterns and environmental factors. Findings are discussed in relation to the epidemiology and control of schistosomiasis and suggestions are made for further spatial studies.

Adolescent↗

PubMed1997

The isolation of a 22 kDa band after SDS-PAGE of Schistosoma mansoni adult worms and its use to demonstrate that IgE responses against the antigen(s) it contains are associated with human resistance to reinfection.

In schistosomiasis endemic areas, intensities of reinfection after treatment are greater amongst young children than amongst adults, and high levels of parasite-specific IgE are associated with resistance to reinfection in an age-dependent manner. Previously we have reported that, in Western blots, a 22 kDa band was recognized by human IgE and that the incidence and intensity of S. mansoni reinfection were significantly lower amongst individuals who had IgE against this band, compared with those who did not (Dunne et al. 1992). Here we report the isolation of a 22 kDa SDS-PAGE band, its incorporation into ELISA and the demonstration that levels of human anti-22 kDa IgE had a significant negative correlation with intensities of subsequent reinfection. Rabbit anti-22 kDa band serum recognized the outer tegument, gut tegument, and the collecting ducts and flame cells of adult worms. The 22 kDa band antigen(s) was also present in "lung'- and "post-lung' schistosomula stages of S. mansoni, and in S. haematobium, S. bovis and S. japonicum adult worms. Metabolic labelling of schistosomula and worms demonstrated the in vitro synthesis and release of 22 kDa antigens.

Animals↗

PubMed1997

Quality control of Kato slide counts for Schistosoma mansoni: a review of 12 years' experience in Kenya.

A total of 19 annual or biannual audits were performed over a 12-year period by an independent microscopist on randomized subsamples of Kato slides examined for Schistosoma mansoni eggs by Kenyan microscopists from the Division of Vector-borne Diseases (DVBD). The recounts were invariably lower than the originals owing to some deterioration of the preparations between counts, but the two were strongly correlated: significant regressions of recounts on counts taking up 80-90% of the observed variance. Observer bias differed significantly between microscopists but remained stable over time, whereas repeatability of recounts on counts dropped slightly in periods of maximum work load but did not vary systematically with time. Approximately 7% of the counts and recounts disagreed on the presence or absence of eggs, but less than a third of these were negatives that were found positive on recount. False negatives dropped to 1.3% if duplicate counts were considered. The performance of the Kenyan microscopists was remarkably high and consistent throughout the 12-year period. This form of quality control is suitable for projects where limited funds preclude full-time supervisors using more sophisticated systems.

Animals↗

PubMed1996

Water contact observations in Kenyan communities endemic for schistosomiasis: methodology and patterns of behaviour.

A descriptive analysis of observed water contact activities in seven Kenyan (Akamba) communities is presented. The patterns of contact with time of day, month of year, type of activity, degree of immersion, use of soap, use of 'kithima' and day of week are all considered, with particular attention given to how these vary with age and sex. It is noted that (a) patterns of contact vary dramatically between these culturally rather similar communities, (b) contact usually peaks in the second decade of life, (c) generally females, especially young women, spend more time at the water than males and (d) simple (unweighted) total observed duration of contact gives a relatively inflated estimate of exposure in adults, especially young women. The methodology of observation and data handling is described in some detail.

Adolescent↗

PubMed1996

Human immunoglobulin E responses to a recombinant 22.6-kilodalton antigen from Schistosoma mansoni adult worms are associated with low intensities of reinfection after treatment.

Schistosoma mansoni-infected individuals who have low intensities of reinfection following treatment produce immunoglobulin E (IgE) antibodies against a range of S. mansoni adult-worm antigens. One of the targets of the IgE response is an adult-worm sodium dodecyl sulfate-polyacrylamide gel electrophoresis band of 22 kDa (Sm22), which contains an antigen(s) located within the tegument and gut lining of adult worms and relatively late schistosomula life cycle stages only. A significant negative correlation between the level of anti-Sm22 IgE and the intensity of reinfection following treatment suggests that IgE responses against this antigen(s) are characteristic of individuals who are resistant to reinfection. To identify the antigen(s) in the Sm22 band that are associated with these IgE responses, we have cloned and characterized a recombinant 22-kDa protein (rSm22) that cross-reacts immunologically with Sm22. There was a high correlation between native and recombinant Sm22 isotype responses, indicating that the correct antigen had been cloned and that responses against rSm22 made up the majority of the responses against Sm22. By analyzing human isotype responses to rSm22 with human sera from a longitudinal treatment and reinfection study and correlating the anti-rSm22 isotype responses, retrospectively, with the intensity of reinfection following treatment for each individual, we observed a negative correlation between the IgE response to rSm22 and the intensity of reinfection. This relationship remained significant after allowing for age and other isotype responses to rSm22, in particular IgG4.

Adolescent↗

PubMed1996

Immunity and morbidity in Schistosoma mansoni infection: quantitative aspects.

Immunity to Schistosoma mansoni infection in humans can be studied most easily by monitoring serially the intensity of reinfection that occurs among individuals who have undergone chemotherapeutic cure, and whose levels of exposure to contaminated water is subsequently observed. Parallel studies can then be made of those immune responses that are correlated with an observed resistance to reinfection. This paper describes some of the difficulties associated with this approach, with particular reference to the authors' own studies in Kenya, and highlights a possible role of immunoglobulin E antibodies against adult worm antigens in mediating immunity.

Age Factors↗

PubMed1996

Age-dependent reduction of schistosome fecundity in Schistosoma haematobium but not Schistosoma mansoni infections in humans.

Understanding the dynamics of schistosome infections is problematic because direct measurements of worm burden are not possible. Hitherto, the relative intensity of infection has been estimated by the number of parasite eggs excreted. Egg excretion is assumed to have a consistent relationship with worm burden with duration of infection. We have tested this assumption in Schistosoma mansoni- and S. haematobium-infected populations by looking at the relationships between a circulating parasite antigen, egg excretion level, host age, and parasite density. The study was carried out in two populations because experimental models suggested that S. haematobium but not S. mansoni suffers immune-mediated reduction of fecundity. The results were consistent with this observation, showing that S. mansoni egg output remains stable irrespective of host age or infection intensity while S. haematobium has a substantially reduced egg production with host age. This information is fundamental to understanding the immunology and epidemiology of human schistosomiasis and thus practical approaches to disease control.

Adolescent↗

PubMed1995

Schistosoma haematobium in the baboon (Papio anubis): assessment of protection levels against either a single mass challenge or repeated trickle challenges after vaccination with irradiated schistosomula.

Baboons vaccinated intramuscularly with three times 9000 20 krad irradiated Schistosoma haematobium schistosomula at monthly intervals were exposed percutaneously to either a single mass challenge of 3000 (VMC) or ten, weekly trickle challenges of 300 (VTC) normals S. haematobium cercariae. Unvaccinated mass (MCC) or trickle (TCC) challenge controls were exposed simultaneously. Faecal and urine egg production was delayed in the vaccinated groups which also had reduced adult, particularly female, worm recoveries. Total faecal, urine and tissue eggs were lower in the vaccinated groups, as also were the size of granulomata and the gross pathology and severity of inflammatory responses in the bladder and ureters, except for an increased proportion of tissue eggs in the livers of vaccinated animals. Differences in pathology between groups were less marked in the other organs. Most indices were reduced in the trickle versus the mass challenge control groups. Some of these trends were statistically significant, mostly in the trickle vaccination group (VTC), but others were not. Compared with the appropriate unvaccinated controls, the percentage reduction for the trickle challenge (VTC) group (73%) was three times greater than that of the mass challenge (VMC) group (23%). Overall, the protective effect of vaccination was more clearly demonstrated in the trickle than in the mass challenge groups. This conclusion is based on a single experiment. Nevertheless, because trickle infections probably approximate more closely to what humans receive naturally, it is recommended that they should be used for future testing of all potential vaccines in baboons.

Animals↗

PubMed1995

A statistical approach to schistosome population dynamics and estimation of the life-span of Schistosoma mansoni in man.

Dynamic models which predict changes in the intensity of schistosome infection with host age are fitted to pre-intervention Schistosoma mansoni data from Kenya. Age-specific post-treatment-reinfection data are used to estimate the force of infection, thus enabling investigation of the rate of worm death. An empirical and statistical approach is taken to the model fitting: where possible, distributional properties and function relationships are obtained from the data rather than assumed from theory. Attempts are made to remove known sources of bias. Maximum likelihood techniques, employed to allow for error in both the pre-intervention and reinfection data, yield confidence intervals for the worm life-span (CI95% = 5.7-10.5 years) and demonstrate that the worm death rate is unlikely to vary with host age. The possibilities and limitations of fitting dynamic models to data are discussed. We conclude that a detailed, quantitative approach will be necessary if progress is to be made with the interpretation of epidemiological data and the models intended to describe them.

Adolescent↗

PubMed1995

Short report: diminished susceptibility to praziquantel in a Senegal isolate of Schistosoma mansoni.

There is a recent report of low efficacy of praziquantel (PZQ) treatment of human schistosomiasis in a new Schistosoma mansoni focus in northern Senegal. Biomphalaria pfeifferi snails with patent infections were collected from the area of the focus and transported to the United Kingdom. Groups of mice were infected with cercariae from this Senegalese isolate, or with laboratory-maintained Kenyan or Puerto Rican isolates. In two separate experiments, PZQ was less effective against the parasite from Senegal than against the two other geographic isolates. The reduced susceptibility of S. mansoni to PZQ in infected human populations has important implications for current schistosomiasis control programs.

Animals↗

PubMed1995

Polyparasitism in two rural communities with endemic Schistosoma mansoni infection in Machakos District, Kenya.

Formol-ether concentration supplemented by fresh saline smears was used to study intestinal parasites in two communities, Miu and Kitengei, in Machakos District, Kenya. These communities differed markedly in schistosome associated morbidity, in spite of similar prevalence and intensities of infection as revealed by Kato examination, Seven helminth and nine protozoan species were detected among 1011 samples examined. More than 60% of the subjects were infected with more than one parasite: one had nine. Age-prevalence curves were typical for the different species, and overall prevalence of some protozoa, including Entamoeba spp. and Blastocystis hominis, exceeded that of the commonest helminth, Schistosoma mansoni. However, the observed prevalence of S. mansoni was barely 40% of that detected by Kato examinations. Strong associations were found between some pairs of protozoan species, but not with or among the helminths. The differences in the abundance and age-specific distribution of the other intestinal parasites at Miu and Kitengei were so small that it is unlikely that interactions between them and S. mansoni would account for the differences in schistosomal morbidity.

Adolescent↗

PubMed1995

Field evaluation of an improved Kato-Katz thick smear technique for quantitative determination of helminth eggs in faeces.

A new method for the quantification of helminth eggs in faeces was developed, in which 7.5% nigrosin in 10% formaldehyde mixed with 5% eosin yellow in 10% formaldehyde was substituted for the malachite green solution used in the standard Kato-Katz method. This modification revealed the eggs of parasites like Schistosoma mansoni, Ascaris lumbricoides, Trichuris trichiura and hookworms distinctly. The slides made with this new technique could be accurately read within one hour. Faecal smears from 100 pupils in Kigungu, Entebbe, Uganda, were studied with both methods. The egg counts of S. mansoni, A. lumbricoides and T. trichiura by both methods were equal. The modified method, however, showed significantly higher hookworm egg counts (p < 0.001). Hookworm eggs were equal one hour after preparation of the slides as 16 hours after preparation. The intensity of infection detected was higher with the modified method for both S. mansoni and hookworms.

Ancylostomatoidea↗