Predisposition and ascaris infection.
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Ascariasis↗
Biomedical subjects
D A Bundy
Publications and source records attributed to D A Bundy.
Trichuris trichiura infection and mental development in children.
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Anthelmintics↗
Parasitic helminth infection and cognitive function in school children.
The study examines the effect of moderate to high worm burdens of Trichuris trichiura infection on the cognitive functions of 159 school children (age 9-12 years) in Jamaica, using a double-blind placebo-controlled protocol. Results were evaluated by using a forward-stepwise multiple linear regression. Removal of worms led to a significant improvement in tests of auditory short-term memory (p less than 0.017; p less than 0.013), and scanning and retrieval of long-term memory (p less than 0.001). Nine weeks after treatment, there were no longer significant differences between the treated children and an uninfected Control group in these three tests of cognitive function. It is concluded that whipworm infection has an adverse effect on certain cognitive functions which is reversible by therapy.
Albendazole↗
The effect of repeated chemotherapy on age-related predisposition to Ascaris lumbricoides and Trichuris trichiura.
This study examines the persistence of predisposition to Ascaris lumbricoides and Trichuris trichiura during repeated chemotherapy in an urban community in Kuala Lumpur, Malaysia. Significant predisposition was observed over 2 periods of reinfection with and without age-standardization of data. Analysis of different age groups indicated that predisposition was most strongly detectable in the younger age classes. The intensities of infection with both parasites were strongly correlated at each cycle of intervention, suggesting that individuals were similarly predisposed to both species.
Adolescent↗
Moderate to heavy infections of Trichuris trichiura affect cognitive function in Jamaican school children.
A double-blind placebo trial was conducted to determine the effect of moderate to high loads of Trichuris trichiura (whipworm) infection on the cognitive functions of 159 school children (age 9-12 years) in Jamaica. Infected children were randomly assigned to Treatment or Placebo groups. A third group of randomly selected uninfected children were assigned to a Control for comparative purposes. The improvement in cognitive function was evaluated using a stepwise multiple linear regression, designed to control for any confounding variables. The expulsion of worms led to a significant improvement in tests of auditory short-term memory (P less than 0.02; P less than 0.01), and a highly significant improvement in the scanning and retrieval of long-term memory (P less than 0.001). After 9 weeks, treated children were no longer significantly different from an uninfected Control group in these three tests of cognitive function. The removal of T. trichiura was more important than Ascaris lumbricoides in determining this improvement. The results suggest that whipworm infection has an adverse effect on certain cognitive functions which is reversible by therapy.
Albendazole↗
Protein content of CBA/Ca mouse diet: relationship with host antibody responses and the population dynamics of Trichuris muris (Nematoda) in repeated infection.
The influence of host dietary protein on acquired immunity and intestinal helminth population dynamics during repeated infection was studied using the mouse-Trichuris muris experimental model. CBA/Ca mice fed a 2% (by mass) protein diet ad libitum maintained body weight during the experiment, but when fed diets containing either 4% or 16% (by mass) protein gained weight steadily. Infection with T. muris did not affect the growth of the latter mice but significantly reduced the growth of animals fed on the 2% protein diet. When repeatedly infected with either 5 or 50 eggs every 10 days, the mice fed the 2% or 4% protein diet accumulated adults in proportion to infection dose. The results show that this is due to both the establishment of larvae at each repeated infection and the survival of established adults. In contrast, very few worms were recovered from animals fed the 16% protein diet, principally as a result of the development of strong acquired immunity to reinfection. T. muris egg output/mouse increased with infection dose in animals fed the low protein diets, but no parasite eggs were detected in the faeces of hosts fed the 16% protein diet. Mouse antibody responses to adult worm excretory/secretory antigen were time- and infection dose-dependent in all 3 dietary groups. The major finding was that the specific antibody response was more intense, both quantitatively (serum OD levels) and qualitatively (antigen recognition by IgG1), in mice fed the low protein diets, even though they remained susceptible to infection. This study shows that host dietary protein deficiency, even at levels irrelevant to normal growth, can markedly potentiate the transmission of T. muris via alterations in host resistance. The high levels of antibody in susceptible animals suggest that this defect in resistance is unlikely to be due to nutrient deficiency-associated defects in humoral immunity.
Analysis of Variance↗
Comparative prevalences of Ascaris lumbricoides, Trichuris trichiura and hookworm infections and the prospects for combined control.
Programmes to control Ascaris lumbricoides, Trichuris trichiura and hookworm infections have often been targeted at each infection separately, but the advent of benign and broad-spectrum anthelmintics suggests that combined control may be feasible. The extent to which the infections co-occur in communities will determine the need for, and potential benefits of, such a combined approach. This paper examines the comparative distribution of the three geohelminths in different geographical areas and shows that A. lumbricoides and T. trichiura have closely related distributions, while hookworm infection is largely independent of the other two. These results indicate that many communities are at risk of disease from infection by more than one species of helminth. The similar distributions and epidemiological characteristics of A. lumbricoides and T. trichiura suggest that simultaneous control of these two parasites by the same strategy would be feasible and highly beneficial to communities. Multiple species control strategies which aim to control hookworm infection may require a more complicated protocol with more precise locality targeting.
Africa, Eastern↗
The relationship between Trichuris trichiura transmission intensity and the age-profiles of parasite-specific antibody isotypes in two endemic communities.
The present study compares parasite-specific antibody responses in two Caribbean communities with high and low levels of Trichuris trichiura transmission. The age-dependency of antibody levels suggest that IgG1 and IgG2 levels relate to the current intensity of infection (as assessed by density of eggs in stool (e.p.g.) and reflect the age-intensity profile at the population level. IgG4, IgE and IgA levels persist into early adulthood and the subsequent decline is gradual. In the low transmission area, lower infection levels are reflected in lower parasite-specific antibody levels (of all isotypes) in the community as a whole. Despite a significantly greater past experience of infection in the high transmission area, antibody levels are not maintained at significantly higher levels throughout adulthood. The production of IgA appears to require a threshold for triggering, and a vigorous IgA response is maintained into early adulthood only in the high transmission village where peak intensity is greatest and the age-convexity of intensity is most marked. Experimental and theoretical studies focusing on the dynamic nature of host-helminth interactions in hosts exposed to high and low infection levels, and the putative role of acquired immunity, are discussed in relation to the data presented.
Adolescent↗
Immuno-epidemiology of human geohelminthiasis: ecological and immunological determinants of worm burden.
The morbidity and transmission dynamics of geohelminthiases are determined by the patterns of infection intensity in the community. Understanding the determinants of these patterns requires a combination of field, laboratory and theoretical study. Studies of age-specific reinfection, and of the phenomenon of predisposition, indicate that the major determinant of convex age-intensity profiles and of heterogeneity in infection intensity is the rate of establishment of infection, rather than the rate of adult worm mortality. The rate of establishment is, in turn, determined by exposure to, and protection from, infection. The evidence indicates that exposure, at least to the orally-transmitted geohelminths, varies with age and is highly heterogeneous between hosts. The immune response in geohelminthiasis is vigorous, parasite-specific, heterogeneous between hosts, and both age and infection dose dependent, but has yet to be convincingly shown to be protective. Since the immune response it itself a function of exposure, unravelling the interaction between ecology and immunology as determinants of geohelminth worm burden will require simultaneous assessment of both processes via immunoepidemiological study.
Age Factors↗
A new approach to morbidity risk assessment in hookworm endemic communities.
The relationship between paired hookworm prevalence and mean intensity of infection data from geographically defined communities was examined. The results show that, in spite of major socio-economic and environmental differences between communities, the relationship is consistent and non-linear. A generalized value of k (the exponent of the negative binomial distribution) for hookworms was estimated to be 0.34, which is consonant with previous estimates from cross-sectional data. Maximum likelihood analysis indicates that the severity of hookworm aggregation in humans has an inverse relationship to mean worm burden which is less marked than for Ascaris lumbricoides. A simple model, based on published estimates of hookworm burdens associated with hookworm anaemia, was used to predict prevalence of morbidity from prevalence of infection data for Tanzania, Kenya and Zambia. Predictions correspond to the observation that hookworm anaemia is highly focal, and largely coastal, in distribution. These analyses suggest that locality-targeting of chemotherapy is particularly appropriate for the control of hookworm morbidity.
Ancylostomiasis↗
Nutrition, immunity and helminth infection: effect of dietary protein on the dynamics of the primary antibody response to Trichuris muris (Nematoda) in CBA/Ca mice.
The effect of dietary protein on the specific antibody responses (total immunoglobulins, IgG1 and IgA) to the intestinal nematode Trichuris muris was studied in CBA/Ca mice fed isocaloric diets containing 16% or 4% protein. Mice fed the 16% diet and given a high infection dose of 650 eggs expelled almost their entire primary infection by day 21 post infection. In similarly infected animals fed the 4% protein diet, there was prolonged survival of adult worms. At a low infection dose of 10 eggs, there was no evidence of an expulsion response in either dietary group. The primary antibody response to parasite excretory/secretory (E/S) antigen was time-dependent, regardless of dietary protein or infection dose, and was predominantly an IgG1 response. Within each dietary group, antibody production and antigen recognition occurred earlier and the antibody responses were more intense in mice given the higher infection dose. The principal finding was that the specific antibody response was more vigorous, both quantitatively (serum titres) and qualitatively (antigen recognition by IgG1), in mice on a low protein diet, even though worm expulsion did not occur in these hosts. This result suggests that serum antibody level or antigen recognition is not related simply to protective immunity against T. muris in CBA/Ca mice.
Animals↗
The effect of repeated chemotherapy on the prevalence and intensity of Ascaris lumbricoides and Trichuris trichiura infection.
The prevalence and intensity of intestinal nematode infections were assessed during 3 anthelminthic interventions in an urban community in Malaysia. The prevalence levels of Ascaris lumbricoides at Interventions 1, 2 and 3 were 30.6%, 18.9% and 15.5%, respectively and the mean intensities were 1.9, 0.75 and 0.81 worms per person. For Trichuris trichiura, the prevalence levels at Interventions 1, 2 and 3 were 46.9%, 21.6% and 15.7%, respectively. The mean intensities for T. trichiura at Interventions 1, 2 and 3 were 3.30, 0.92 and 0.07 worms per person. No gender-related prevalence and intensity were observed for the two geohelminths in this community. Prevalences and intensity had convex age profiles. Although repeated chemotherapeutic intervention reduced both prevalence and intensity levels, intensity was a more sensitive indicator than prevalence. The results indicate that age-targetting treatment at school children of 7-12 years of age would be an appropriate strategy for this community.
Adolescent↗
Evaluating measures to control intestinal parasitic infections.
Intestinal parasitic infections are among the most common infections of humans in developing countries, but the resources available for their control are severely limited. Careful evaluation of control measures is essential to ensure that they are cost-effective. The evaluation of the effects of control on intestinal helminths and intestinal protozoa requires an understanding of the different epidemiological patterns of these two groups of parasites. The transmission dynamics and morbidity associated with the major helminth infections (Ascaris lumbricoides, Trichuris trichiura and the hookworms) are dependent on the size of the worm burdens. Thus the important parameter for evaluating the impact of control on morbidity and transmission is the intensity of infection, which can be assessed by determining the mean density of parasite eggs in faecal specimens. Estimation of intensity is subject to systematic errors, however, due to the complex pattern of worm burden distributions. The frequency distribution of burdens is highly overdispersed, and individuals exhibit predisposition to particular levels of infection. Furthermore, mean intensity is age-dependent, in a species-specific manner, and is clustered spatially and within families. These complex patterns imply that the estimation of intensity is exceptionally sensitive to the size and demographic structure of the population sample selected for assessment. They also have the effect that prevalence estimates, the most commonly used measures of infection in communities, can seriously mislead. Paradoxically, prevalence is least useful where infection is most common because the relationship between prevalence and intensity is most markedly non-linear when the prevalence is high. Thus in areas where control is most needed, evaluation using prevalence might suggest that control had failed while evaluation by intensity would, correctly, show the measure of success. With the major protozoan infections (Entamoeba histolytica, Giardia duodenalis and Cryptosporidium parvum) an estimate of intensity is of little value and the central parameter for evaluation is prevalence. Prevalence does exhibit age and spatial heterogeneity, which may be species-specific, so there remains a need to ensure a consistent sample structure, although this is less critical than for the helminths. The major constraint on evaluating the control of protozoan infections is the need to identify pathogenic species and, in some cases, pathogenic strains. Harmless commensal protozoans are ubiquitous and often morphologically very similar to pathogens, but their control is both unnecessary and impracticable. Species such a E. histolytica appear to exist as strains with differing pathogenicity, thus control will be cost-effective only if the focus is on pathogenic strains. Effective diagnosis is therefore central to the evaluation of the control of protozoan infections.(ABSTRACT TRUNCATED AT 400 WORDS)
Adolescent↗
Immediate hypersensitivity in colon of children with chronic Trichuris trichiura dysentery.
There are few data on mucosal immune responses to intestinal helminths in human beings, especially those involving the IgE system, which is thought to be important in parasite expulsion. We sought evidence of an immediate hypersensitivity reaction in the colon of children with chronic dysentery due to Trichuris trichiura. 28 children with Trichuris dysentery syndrome (TDS) were compared with 16 control children (with no TDS or worms visible on colonoscopy). All children were aged 1-11 years. Rectal biopsy samples were taken before and after expulsion of the worms by means of mebendazole treatment. Children with TDS had significantly greater numbers than controls of mast cells (mean [SD] 10.9 [1.3] vs 3.9 [0.6]% of all cells; p less than 0.0003) and of cells with surface IgE (median [range] 11.1 [7.5-11.6] vs 1.0 [0-1.5]%; p less than 0.001) in the subepithelial region of the mucosa. On electronmicroscopy, degranulating mast cells were prominent in parasitised children. In culture, rectal biopsy samples from parasitised children showed high rates of spontaneous histamine release, but only low rates of antigen-specific release. After treatment, spontaneous histamine release was significantly reduced and antigen-specific histamine release could be provoked. Thus, an IgE-mediated immune mucosal response to a helminth infection does occur in human beings but is not sufficient to cause appreciable parasite expulsion.
Anaphylaxis↗
Immunoepidemiology of lymphatic filariasis: the relationship between infection and disease.
Lymphatic filariasis is manifested by a spectrum of symptoms that range from microfilaraemia to gross immunopathology. The geographical variations seen in this disease have been explained by heterogeneity in genetically determined host responses. By modelling the disease through time, Don Bundy, Bryan Grenfell and P.K. Rajagopalan can provide a simple, unified explanation for the observed heterogeneity. Their model shows that there is a sequential progression from infection, microfilaraemia, amicrofilaraemia to obstructive disease in all individuals who experience microfilaraemia. Only the probability of developing microfilaraemia is geographically variable, being dependent on the local incidence of infection.
Africa↗
The effect of the protein content of CBA/Ca mouse diet on the population dynamics of Trichuris muris (Nematoda) in primary infection.
The relationship between host dietary protein and intestinal helminth population biology during primary infection was studied using a mouse-T. muris experimental model. Uninfected CBA/Ca mice fed either a 4% (by mass) or 16% protein diet grew at a similar rate, but both suffered significant growth retardation when infected with T. muris. T. muris initial establishment and fecundity were unaffected by dietary protein content, but were significantly influenced by infection dose, declining at the higher level of infection. Dietary protein deficiency increased parasite survival at high infection levels. Heavily infected hosts fed the 16% protein diet were found to expel almost the whole of their infections around day 21 p.i. By contrast, this response appeared defective in hosts fed the lower 4% protein diet, resulting in the establishment and survival of large, chronic and patent infections. Mean faecal egg output per mouse increased with infection dose in animals fed a low protein diet, but was low and unrelated to infection exposure in hosts fed the 16% protein diet. It is concluded that low protein levels in diet, via alterations in host resistance, may have an important influence on the transmission of T. muris.
Analysis of Variance↗
Frequency distribution of Brugia malayi microfilariae in human populations.
This study examines the effects of host age and sex on the frequency distribution of Brugia malayi infections in the human host. Microfilarial (mf) counts for a large data base on the epidemiology of brugian filariasis in Shertallai, Kerala, South India are analysed. Frequency distributions of microfilarial counts partitioned by age are successfully described by zero-truncated negative binomial distributions, fitted by maximum likelihood. This analysis provides estimates of the proportion of mf-positive individuals who are identified as negative due to sampling errors, allowing the construction of corrected mf age-prevalence curves, which indicate that the observed prevalence may under-estimate the true figures by between 18 and 47%. There is no evidence from these results for a decrease in the degree of over-dispersion of parasite frequency distributions with host age, such as might be produced by the acquired immunity to infection. This departure from the pattern in bancroftian filariasis (where there is evidence of such decreases in over-dispersion; Das et al. 1990) is discussed in terms of the long history of filariasis control (and consequently low infection prevalence) in Shertallai.
Adolescent↗
Humoral immune responses in human infection with the whipworm Trichuris trichiura.
The humoral immune response to infection with Trichuris trichirua was investigated by ELISA and immunoblotting using human sera from the Caribbean island of St Lucia. Immunoblot analysis of the degree of cross-reactivity with the related trichuroid Trichinella spiralis and with the other commonly co-existent nematodes, Ascaris lumbricoides and Toxocara canis, was carried out using selected sera. The IgM, IgA, IgE, and IgG subclass antibody levels were measured in ELISA using a detergent solubilized extract of adult T. trichiura. The IgG and IgE responses were highly Trichuris specific. Anti-T. trichiura IgM responses were totally cross-reactive with A. lumbricoides and were completely ablated by pre-incubation of sera with Ascaris antigen. The IgG response was predominantly of the IgG1 subclass with a minimal IgG3 response. Only 1 person out of 130 tested had a detectable IgG3 response. The IgG2 response appeared to be directed primarily against carbohydrate or polysaccharide antigens as pre-treatment of the ELISA plates with poly-L-lysine was necessary before a response could be detected. These data are the first demonstration of human isotypic responses to infection with T. trichiura.
Animals↗