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Biomedical subjects

A E Butterworth

Publications and source records attributed to A E Butterworth.

At least 19 recordsLinked to original sources
PubMed2001

Prevalence and familial aggregation of schistosomal liver morbidity in Kenya: evaluation by new ultrasound criteria.

Severe periportal fibrosis is not an inevitable consequence of infection with Schistosoma mansoni. Genetic predisposition may be a deciding factor in the development of disease. To assess the contribution of genetic factors in the severity of hepatic fibrosis, the degree of familial aggregation was determined in a Kenyan population. Schistosomal fibrosis was identified with hepatic ultrasound and newly proposed World Health Organization criteria, which include both qualitative and quantitative observations. These 2 aspects of the criteria correlated well with one another. The peak prevalence of ultrasound proven fibrosis trailed 5-10 years behind peak prevalence of infection and declined sharply after age 50 years. This pattern was consistent with either resolution of severe fibrosis over 10-20 years or early death of those severely affected. Genetic predisposition appears to be a weak factor in the development of severe disease in this population, since no household or familial aggregation could be identified.

Adolescent↗
PubMed2000

Sex-dependent neutralizing humoral response to Schistosoma mansoni 28GST antigen in infected human populations.

The reduction of Schistosoma fecundity observed after experimental vaccination with the Schistosoma mansoni 28-kDa glutathione S-transferase (Sm28GST) antigen has been related to the inhibition of glutathione S-transferase (GST) enzymatic activity by specific antibody. The humoral immune response to the protective antigen Sm28GST and to the epitopes involved in the enzymatic site (amino acid ¿aa sequences 10-43 and 190-211) was evaluated in infected individuals before chemotherapy treatment. The capacity of the serum samples to inhibit GST enzymatic activity was assessed. Specific IgG3 response was predominant in the male population with a low intensity of infection and was associated with maximal GST inhibition. In contrast, the neutralizing activity of serum samples from women with a low intensity of infection was correlated with high specific IgA response specifically directed toward the 190-211 epitope. These results strongly support the hypothesis that GST-neutralizing IgG3 and IgA isotypes are sex dependent. The relationship of this specific acquired immune response with the level of intensity of infection is discussed.

Adolescent↗
PubMed1999

Adult resistance to schistosomiasis mansoni: age-dependence of reinfection remains constant in communities with diverse exposure patterns.

In a fishing community on Lake Albert in Uganda the pattern of intensity of Schistosoma mansoni infection 6 months after treatment with praziquantel was found to be very similar to reinfection patterns seen in previously studied endemic communities: the profile peaks sharply at around the age of 10 years falling away rapidly to much lower levels in adults. This is in stark contrast to the patterns of water contact, which differ greatly between fishing and non-fishing communities. On Lake Albert, adults appear to be more heavily exposed than children. From these observations we conclude that adults are physiologically (perhaps immunologically) more resistant to infection after treatment than children.

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↗
PubMed1999

Development of antibody isotype responses to Schistosoma mansoni in an immunologically naive immigrant population: influence of infection duration, infection intensity, and host age.

We have identified the influence of host and parasite factors that give rise to characteristic antibody isotype profiles with age seen in human populations living in different areas of schistosomiasis endemicity. This is important in the immunobiology of this disease. It is also of interest in the context of human responses to chronic antigen stimulation, vaccines, allergens, and other pathogens. In populations exposed to endemic schistosomiasis, factors such as intensity and duration of infection are age dependent. They therefore confound the influence of host age on antiparasite responses. Here, we resolved these confounding factors by comparing the developing antibody responses of an immunologically naive immigrant population as they acquired the infection for the first time with those of chronically infected resident inhabitants of the same region of Schistosoma mansoni endemicity in Kenya. Recent arrival in the area strongly favored immunoglobulin G3 (IgG3) responses against the parasite. The antibody isotype responses associated with human susceptibility to reinfection after chemotherapy were elevated in those suffering high intensities of infection (IgG4 responses against worm and egg antigens) or were characteristic responses of young children irrespective of the intensity or duration of infection (IgG2 responses against egg antigen). IgE responses against the adult worm, a response associated with resistance to reinfection after chemotherapy, increased with the ages of infected individuals and were also favored in those currently suffering higher intensities of infection.

Adult↗
PubMed1998

High levels of TNF, soluble TNF receptors, soluble ICAM-1, and IFN-gamma, but low levels of IL-5, are associated with hepatosplenic disease in human schistosomiasis mansoni.

In a case-control study based in two areas of Kenya, hepatosplenic schistosomiasis mansoni was shown to be linked with low levels of IL-5 and with correspondingly high IFN-gamma, TNF, and circulating soluble TNF receptor I (sTNFR-I), sTNFR-II, and sICAM-1. PBMC from the hepatosplenic cases responded to in vitro Ag stimulation with significantly higher levels of IFN-gamma and TNF, but lower levels of IL-5, compared with nonhepatosplenic controls matched for age and infection intensity. Most of these correlations were confounded by differences between geographical areas. However, principle component analysis identified a high IFN-gamma and TNF, and low IL-5 axis in the data as the first principle component; this was significantly associated with hepatosplenomegaly (p < 0.0005) even after controlling for area. High plasma levels of sTNFR-I (p < 0.001), sTNFR-II, (p < 0.0001), and sICAM-1 (p < 0.009) were also significantly associated with hepatosplenomegaly, independently of area, in the case of the soluble forms of both TNF receptors. These parameters were negatively related to IL-5. These results suggest that proinflammatory cytokines are involved in the hepatosplenic disease process in infected individuals who have low anti-inflammatory Th2 responses and that sTNFR may be a useful circulating marker for this disease process, perhaps reflecting the level of TNF activity in hepatic tissues.

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↗
PubMed1998

Immunological aspects of human schistosomiasis.

Helminth infections are characteristically associated with Th2-dependent responses leading to IgE production and eosinophilia. However, the effect of such responses varies between different hosts. In murine schistosomiasis, for example, Th1 responses are associated with protection against infection, and Th2 responses with egg-induced morbidity. In human schistosomiasis, in contrast, Th2 responses with the production of IgE antibodies against a restricted range of adult worm antigens are associated with protection against reinfection after chemotherapy, while individuals in whom Th2 responses against egg antigens predominate show less severe egg-associated morbidity than those in whom Th1 responses predominate. It is suggested that Th2-mediated responses are selectively advantageous to the human host in the context of schistosomiasis and possibly other helminth infections. The implications of this for vaccination, for control through chemotherapy, and for the study of interactions with other infections are briefly discussed.

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 influence of sex and age on antibody isotype responses to Schistosoma mansoni and Schistosoma japonicum in human populations in Kenya and the Philippines.

We have investigated the effects of host age and sex on human antibody isotype responses to Schistosoma mansoni and Schistosoma japonicum adult worm (AW) and soluble egg (SEA) antigens, using sera from subjects in Kenya and the Philippines. Similar trends with age were observed between the two populations despite host, parasite and environmental differences between the two geographical locations. IgE to AW increased with age, whereas most isotype responses to SEA decreased with age. IgG1, IgG3 and IgG4 subclass responses to adult worm, however, did not show a broadly rising or falling pattern with age. Males were found to have higher IgG1, IgG4 and IgE to AW in both populations. This sex difference remained significant in the Kenyan population even after controlling statistically for confounding factors such as age and differences in intensity of infection. Analysis of S. mansoni and S. japonicum adult worm antigens reactive with IgE revealed a predominant 22 kDa band in both parasites. Only those individuals with relatively high IgE titres specifically reactive with S. mansoni or S. japonicum AW had detectable IgE against Sj22 or Sm22.

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

Effect of praziquantel and oxamniquine treatment on human isotype responses to Schistosoma mansoni: elevated IgE to adult worm.

Pre- and post-treatment antibody isotype responses to Schistosoma mansoni adult worm and soluble egg antigens were compared in a study population previously used to show that IgE against adult worm correlates negatively with intensity of reinfection following chemotherapeutic cure. IgG subclass responses to adult worm were lower after treatment whereas IgM and IgE were higher. The increase in IgE to adult worm was observed with different preparations of adult worm, including the worm tegument, and with both praziquantel and oxamniquine therapy. No significant difference was observed between pre- and post-treatment isotype responses to egg antigens following either praziquantel or oxamniquine therapy.

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↗