Biomedical subjects

D A Bundy

Publications and source records attributed to D A Bundy.

At least 73 records · Page 4Linked to original sources

PubMed1995

Identification and characterization of excreted/secreted products of Trichuris trichiura.

This study provides the first description of the range and immunogenicity of proteins excreted and/or secreted by living T. trichiura adult worms following their recovery from the human large intestine. Metabolic labelling of T. trichiura excretory/secretory (ES) products with [35S]-methionine revealed a range of proteins with prominent components at 52-54 kDa, 35-45 kDa & 17 kDa. In contrast, the major component of unlabelled T. trichiura ES, somatic whole worm and isolated stichosome extracts, and of [35S]-methionine labelled somatic extracts, was present at approximately 47 kDa. Similarly, the major 43 kDa protein present in unlabelled T. muris ES, somatic worm extract and [35S]-methionine labelled somatic worm extract, was only weakly detected in labelled T. muris ES. Pulse chase experiments demonstrated that after 20 h, the 43 kDa was a prominent component of T. muris ES. These data suggest that the 43/47 kDa protein of Trichuris adult worms is not a major constituent of newly synthesized ES but is either synthesized at a slower rate than other proteins, or sequestered or stored, most likely in the stichocytes, before release. Immunoprecipitations using a range of sera from T. trichiura-infected individuals demonstrated that many of the ES components are immunogenic. Antibody responses were vigorous in children with intense infections and negligible in parasitologically negative children. There was marked heterogeneity in responses to a 17 kDa antigen, with the age profile of anti-17 kDa antibody levels reflecting age-dependent infection intensities at the population level.

Adolescent↗

PubMed1995

Epidemiology of human hookworm and Ascaris lumbricoides infestations in rural Gambia.

In a cross-sectional study of helminth infections in a rural village in The Gambia, West Africa, hookworm, probably Necator americanus and Ascaris lumbricoides were found to be the most prevalent helminths present at prevalence levels of 30% and 25% respectively. Other parasites present were Trichuris trichiura (2.4%) and Schistosoma mansoni (1.5%). The mean egg counts of N. americanus and A. lumbricoides in all age groups and in the total population were low. Egg counts between age and sex groups were not statistically significant. The frequency distributions of both N. americanus and A. lumbricoides were overdispersed with the majority of the sample population producing none or few eggs, and a small minority producing relatively large amounts of eggs. Large variance: mean ratios within age groups and the total study population suggested a high degree of aggregation of the parasites in this community.

Adolescent↗

PubMed1994

The association between microfilaraemia and disease in lymphatic filariasis.

A standard tenet in the epidemiology of lymphatic filariasis is that patent infection is negatively related to chronic disease. We examine the empirical evidence for this relation by using published data from field studies carried out in a variety of bancroftian filariasis endemic areas. Meta-analysis of the individual study results for each disease category of hydrocele in males only, lymphoedema only, and both conditions combined (total chronic disease) indicate, contrary to expectation, no evidence for a negative association between infection and disease. Indeed, the trend of the empirical evidence is towards the opposite direction, with the majority of studies showing equal propensity of disease in microfilaraemics (mf+ves) and amicrofilaraemics (mf-ves), and more studies indicating a positive rather than a negative relation. There was also a trend for more positive studies for hydrocele compared to lymphoedema. Theoretical analysis suggests that between-study differences in blood sample volumes are unlikely to confound this finding. Analysis of between-study heterogeneity suggests that variations in the local incidence or prevalence of infection rather than unique geographical, including vector, differences might underlie the observed between-study variability in the microfilaraemia-disease association. These results are discussed in terms of dynamic explanations for infection-disease relations in lymphatic filariasis.

Animals↗

PubMed1994

Strongyloides stercoralis: characterization of immunodiagnostic larval antigens.

Forty-one-, 31-, and 28-kDa proteins of Strongyloides stercoralis filariform larvae have previously been demonstrated to be sensitively and specifically recognized by serum IgG in individuals with strongyloidiasis. Characteristics of these proteins, their immunodominant epitopes, and reactive antibodies are described here. The proteins are soluble in aqueous as well as detergent extracts. The immunodominant epitopes are present in S. stercoralis but not in S. cebus or S. ratti. Epitopes on the three proteins are not shared, as determined by cross-adsorption of serum with each of the size components on nitrocellulose. In most sera from strongyloidiasis patients there was reactivity to each of the proteins by IgG1 and IgG4, but reactivity by IgG2 or IgG3 was detectable only in a minority. A rabbit antiserum raised to a 41-kDa size fraction of S. stercoralis larvae reacted against a doublet of 41-kDa which was distinct from the immunodiagnostic 41-kDa protein.

Animals↗

PubMed1994

Comparison of age-dependent antigen recognition in two communities with high and low Trichuris trichiura transmission.

A previous ELISA-based study using whole worm extract, compared age-antibody profiles in two communities with high and low levels of Trichuris trichiura transmission (Needham et al., 1992). This showed that specific IgG1 levels mirrored infection intensity at the population level, while IgA levels exhibited a weak trend to remain elevated in the adult age classes in the area of highest transmission. This was interpreted as preliminary evidence for IgA-mediated resistance in the population with greatest prior experience of infection. The present study extends this work to compare IgG1 and IgA isotype recognition of separated antigens by Western blot between the two communities. Comparison of age-dependent antigen recognition in the two communities shows that both qualitative and quantitative recognition by IgG1 antibodies is related to the current intensity of infection (as assessed by eggs per gram of faeces, epg). The magnitude of the IgA response to separated antigens of 16-17 kDa and 90 kDa exhibits a stronger trend to remain elevated in adults and to reflect the past experience of infection: IgA antibodies are present at significantly higher levels in adults from the high transmission area compared with those from the community with low levels of T. trichiura endemicity, despite infection levels in these age groups being of similar magnitude. This comparative study therefore, provides further evidence to support a role for IgA in acquired immunity to T. trichiura in areas of intense transmission.

Adolescent↗

PubMed1994

Does helminth infection affect mental processing and educational achievement?

In this article, Catherine Nokes and Donald Bundy reexamine the evidence linking intestinal helminth infection to impaired cognitive function and educational outcomes. They consider first the evidence that implies a connection between intellectual dysfunction and the sequelae of infection, then the significance of correlations between infection and poor mental status, and finally the evidence from case-control and double-blind intervention studies. The article is not intended as a comprehensive summary of all the research on helminth infection and mental function - indeed the majority of research undertaken in the early part of this century is not included - but rather as a thought provoking article to highlight the difficulties with interpreting existing data and to stimulate new interest in this field.

Journal Article↗

PubMed1994

Temporal changes in Trichuris trichiura infection intensity and serum isotype responses in children.

The present study describes Trichuris trichiura infections in a cohort of children over a period of approximately 5 years, and examines the relationships between changes in infection intensity and changes in parasite-specific isotype responses (measured by ELISA). The decrease in mean infection intensity with time was mirrored by time-dependent changes in IgG subclass responses, with IgA and IgE levels remaining relatively constant in the cohort. At the individual level, changes in infection intensity between the initial and final time-points correlated positively and significantly with changes in all isotype levels with the exception of IgA.

Animals↗

PubMed1994

Characterization of peptidases of adult Trichuris muris.

Excretory/secretory (E/S) material of Trichuris muris was found to contain 2 major peptidases, M(r) 85 and 105 kDa, which degrade gelatin optimally at pH 6.0 in sodium dodecyl sulphate-polyacrylamide gels. The peptidases were inactivated by diisopropylfluorophosphate, leupeptin and soybean trypsin inhibitor, but were unaffected by inhibitors of aspartic-, cysteine- and metallo-peptidases, indicating that they are serine peptidases. Both enzymes were detectable within 5 h after incubation of worms in culture medium and showed a time-dependent increase in levels. Neither peptidase was detected in worm extracts, suggesting that they are activated during or following secretion from worms. Live worms degraded a radio-isotope labelled extracellular matrix protein substratum derived from mammalian cells. Aminopeptidase activities capable of catalysing hydrolysis of amino acyl aminomethylcoumarin (MCA) substrates and a Z-Phe-Arg-MCA-hydrolysing cysteine peptidase activity, were detected in extracts of adult worms but not in E/S material.

Amino Acid Sequence↗

PubMed1994

The evaluation of potential global morbidity attributable to intestinal nematode infections.

This paper presents a method of estimating the potential global morbidity due to human intestinal nematode infections (Ascaris lumbricoides, Trichuris trichiura and hookworms), based on the observed prevalence of infection. The method relies on the observed relationships between prevalence and intensity of infection, and between worm burden and potential morbidity. This approach is shown to be sensitive to the precision of the original prevalence estimates and, in particular, to the degree of spatial heterogeneity in levels of infection. The estimates presented here indicate that several tens of millions of children are likely to suffer developmental consequences from infection, and suggest that the global disease burden of geohelminthiasis may be significantly greater than was supposed.

Adolescent↗

PubMed1994

The development and validation of an age-structured model for the evaluation of disease control strategies for intestinal helminths.

Epidemiological modelling can be a useful tool for the evaluation of parasite control strategies. An age-structured epidemiological model of intestinal helminth dynamics is developed. This model includes the explicit representation of changing worm distributions between hosts as a result of treatment, and estimates the morbidity due to heavy infections. The model is used to evaluate the effectiveness of different programmes of age-targeted community chemotherapy in reducing the amount of morbidity due to helminth infection. The magnitude of age-related heterogeneities is found to be very important in determining the results of age-targeted treatment programmes. The model was verified using field data from control programmes for Ascaris lumbricoides and Trichuris trichiura, and was found to provide accurate predictions of prevalence and mean intensities of infection during and following different control regimes.

Adult↗

PubMed1994

Genetic relatedness as a determinant of predisposition to Ascaris lumbricoides and Trichuris trichiura infection.

The present study examines the role of host genetics in predisposition to Ascaris lumbricoides and Trichuris trichiura infection, by comparing the associations between age-standardized infection intensities of parents and their children (genetically related), with age-standardized infection intensities of parents alone (not related), within families previously demonstrated to exhibit familial predisposition. The lack of a consistent trend in infection intensity associations within families, in particular the lack of a stronger association between parents and their children than between unrelated parents, suggests that host genetic factors are not a major determinant of infection status. If there is a genetic basis for predisposition, then the data suggest that the effects of this genetic basis are overwhelmed by other, environmental or behavioural features of the family household.

Adolescent↗

PubMed1994

Prospective evaluation of enzyme-linked immunosorbent assay and immunoblot methods for the diagnosis of endemic Strongyloides stercoralis infection.

Recently described enzyme-linked immunosorbent assay (ELISA) and immunoblot methods for the detection of serum IgG against Strongyloides stercoralis larval antigens were prospectively evaluated for the diagnosis of endemic strongyloidiasis. A modification of the ELISA involved preincubation of sera with Onchocerca gutturosa phosphate-buffered saline-soluble extract to remove cross-reactivity with other helminths. The sensitivity of the ELISA increased from 80% to 85% following preincubation. Similarly, there was an increase in specificity from 94% to 97%. The IgG recognition of 41-, 31-, and 28-kD filariform larval components showed sensitivities of 100%, 85%, and 65%, respectively. Both the ELISA following incubation of sera with O. gutturosa extract and serum IgG reactivity to a 41-kD larval component using immunoblotting are sensitive and specific techniques for diagnosing endemic strongyloidiasis.

Animals↗

PubMed1993

Immunological modulation and evasion by helminth parasites in human populations.

Helminth parasites are highly prevalent in human communities in developing countries. In an endemic area an infected individual may harbour parasitic worms for most of his or her life, and the ability of these infections to survive immunological attack has long been a puzzle. But new techniques are starting to expose the diverse mechanisms by which these agents modulate or evade their hosts' defences, creating a dynamic interaction between the human immune system and the parasite population.

Animals↗

PubMed1993

A quantitative framework for evaluating the effect of community treatment on the morbidity due to ascariasis.

There is growing emphasis on the use of community treatment to reduce the level of morbidity caused by helminth infection. The design of chemotherapy programmes, in terms of frequency of treatment and proportion of the community treated, would be assisted by a quantitative framework which enabled the morbidity reduction achieved by different approaches to be compared. The present study describes a model developed for this purpose which embodies two innovative features. First, a quantitative score of morbidity (the proportion of individuals harbouring an intense infection) is used to rate the success of a programme and, second, the distribution of helminths in the host population is generated by a mechanism that allows the distribution to change dynamically as a function of both treatment and reinfection. The model behaviour, using values typical of Ascaris lumbricoides, indicates that the benefit derived from community chemotherapy increases non-linearly with the coverage and efficacy of treatment.

Animals↗

PubMed1993

Estimation of intestinal nematode prevalence: influence of parasite mating patterns.

Prevalence of infection with intestinal helminths is usually assessed through stool examination. There are limitations in using this technique to measure infection status, since some infected individuals have no patent infection. The relationship between infection assessed by stool examination and actual infection prevalence is investigated for the three major nematode species--Ascaris lumbricoides, Trichuris trichiura and the hookworms--using a model which describes the presence of non-egg producing worm combinations. The analysis demonstrates that stool examination under-estimates the actual infection prevalence, and that the degree of under-estimation is dependent on the level of infection, the nematode species and the parasite sex ratio. These findings have implications for the validity of epidemiological surveys and the evaluation of control programmes.

Animals↗

PubMed1993

The age of infection with varicella-zoster virus in St Lucia, West Indies.

Sera from an age-stratified sample of 1810 people from the Caribbean island of St Lucia were tested for antibodies against varicella-zoster virus. The results indicate that very few infections occur in childhood, which agrees with clinical survey data from other tropical countries, but contrasts with the observed high case rate in children in temperate countries. The alternative hypotheses which may explain these results are discussed, and it is suggested that high ambient temperatures interfere with the transmission of the virus. Irrespective of the cause, the pattern of varicella incidence observed has important implications for any vaccination policy adopted in tropical countries.

Adolescent↗

PubMed1993

Serum IgG reactivity with 41-, 31-, and 28-kDa larval proteins of Strongyloides stercoralis in individuals with strongyloidiasis.

Proteins from a deoxycholate-soluble extract of Strongyloides stercoralis infective larvae were separated by SDS-PAGE, blotted onto nitrocellulose paper, and reacted with sera from individuals with confirmed S. stercoralis infections (n = 100), suspected S. stercoralis infections in whom no larvae could be detected (n = 27), and other nematode infections (40 with Wuchereria bancrofti, 20 with Onchocerca volvulus, 20 with Necator americanus, and 20 with mixed Ascaris lumbricoides and Trichuris trichiura infections). Immunodominant proteins of approximately 41, 31, and 28 kDa were recognized by IgG in 91%, 88%, and 90%, respectively, of sera from those with confirmed strongyloidiasis; in 100%, 100%, and 93% of sera from those with suspected strongyloidiasis; and in 9%, 12%, and 14% of sera from those infected with other nematodes. IgG reactivity to each of these proteins was a more specific means of immunodiagnosis than the currently used indirect ELISA; the methods were equally sensitive.

Animals↗

PubMed1993

Age-dependency of serum isotype responses and antigen recognition in human whipworm (Trichuris trichiura) infection.

The present study examines the age-dependency of parasite-specific isotype responses and antigen recognition profiles of individuals within a Trichuris trichiura endemic community, in order to evaluate the significance of serum antibodies as determinants of observed age-related patterns of infection intensity. A high degree of individual heterogeneity is observed in isotype responses to separated T. trichiura antigens by Western blot. Recognition by IgG1 antibodies exhibits marked age-dependency. The age-profiles of IgG1 responses to selected antigens of 16-17 kDa and 90 kDa molecular weight reflect the age-related changes in current infection intensity at the population level. Similarly, mean age patterns of IgG2 responses to a 90 kDa antigen, and mean IgG4 responses to a 16-17 kDa antigen reflect mean infection levels. IgG3 responses are negligible, and for methodological reasons, both IgE and IgM specificities are not presented. IgA responses to separated antigens of 16-17 kDa and 90 kDa, exhibit age-profiles which may suggest the development of an IgA-mediated acquired resistance to T. trichiura with age. IgA levels remain elevated throughout early adulthood, when infection intensity levels markedly decrease, supporting the hypothesis that IgA antibodies may be significant in generating the convex nature of the age-infection profile of T. trichiura.

Adolescent↗