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Biomedical subjects

D A Bundy

Publications and source records attributed to D A Bundy.

At least 109 records · Page 6Linked to original sources

Age-dependency of infection status and serum antibody levels in human whipworm (Trichuris trichiura) infection.

This study examines the age-dependency of the relationships between human infection with whipworm (Trichuris trichiura) and parasite-specific antibody level measured by ELISA against an extract of adult worms after preincubation of the sera with Ascaris lumbricoides adult worm extract. The convex age-profile of parasite infection intensity is shown to be mirrored by an age-dependent change in age-class mean levels of IgG (all subclasses except IgG3), IgA, IgM and IgE. Mean antibody levels rise with increasing acquisition of infection in childhood and decline as the intensity of infection falls in adulthood. Immunoblot analysis of selected sera from different age-classes indicates that antigen recognition is similarly dependent on infection intensity. In individual children, antibody levels correlate positively with acquisition of infection, consistent with a simple model of antigen dosage specifying the magnitude of the humoral immune response. In adults, IgG4 correlates positively and IgA negatively with intensity of infection, suggesting involvement of these isotypes in functional roles of immune blockade or effector mechanisms, respectively.

Adolescent↗

Histopathology and immunohistochemistry of the caecum in children with the Trichuris dysentery syndrome.

Caecal biopsy specimens from Jamaican children with the Trichuris dysentery syndrome (TDS) and age matched Jamaican controls were investigated by immunohistochemistry and by light microscopy. Biopsy specimens from all children (with TDS and controls) showed a mild to moderate increase in inflammatory cells. Except in the vicinity of the worm, where the epithelium was flattened, there was no other epithelial abnormality. Compared with controls, children with TDS had increased IgM lamina propria plasma cells and decreased intraepithelial T cells. There was also an increase in crypt epithelial cell proliferation. Lamina propria T cells (both activated and non-activated) were no more common in children with the Trichuris syndrome than controls. Epithelial cell HLA-DR and VLA-1 expression (which are increased in other colitides) were the same in both groups. Despite the presence of large worm burdens and chronic dysentery, therefore, only minor changes were seen in the caecal mucosa of children with TDS.

Antigens, CD↗

Frequency distribution of lymphatic filariasis microfilariae in human populations: population processes and statistical estimation.

This paper uses simple mathematical models and statistical estimation techniques to analyse the frequency distribution of microfilariae (mf) in blood samples from human populations which are endemic for lymphatic filariasis. The theoretical analysis examines the relationship between microfilarial burdens and the prevalence of adult (macrofilarial) worms in the human host population. The main finding is that a large proportion of observed mf-negatives may be 'true' zeros, arising from the absence of macrofilarial infections or unmated adult worms, rather than being attributable to the blood sampling process. The corresponding mf distribution should then follow a Poisson mixture, arising from the sampling of mf positives, with an additional proportion of 'true' mf-zeros. This hypothesis is supported by analysis of observed Wuchereria bancrofti mf distributions from Southern India, Japan and Fiji, in which zero-truncated Poisson mixtures fit mf-positive counts more effectively than distributions including the observed zeros. The fits of two Poisson mixtures, the negative binomial and the Sichel distribution, are compared. The Sichel provides a slightly better empirical description of the mf density distribution; reasons for this improvement, and a discussion of the relative merits of the two distributions, are presented. The impact on observed mf distributions of increasing blood sampling volume and extraction efficiency are illustrated via a simple model, and directions for future work are identified.

Animals↗

Frequency distribution of Wuchereria bancrofti microfilariae in human populations and its relationships with age and sex.

This paper examines the effects of host age and sex on the frequency distribution of Wuchereria bancrofti infections in the human host. Microfilarial counts from a large data base on the epidemiology of bancroftian filariasis in Pondicherry, South India are analysed. Frequency distributions of microfilarial counts divided by age are successfully described by zero-truncated negative binomial distributions, fitted by maximum likelihood. Parameter estimates from the fits indicate a significant trend of decreasing overdispersion with age in the distributions above age 10; this pattern provides indirect evidence for the operation of density-dependent constraints on microfilarial intensity. The analysis also provides estimates of the proportion of mf-positive individuals who are identified as negative due to sampling errors (around 5% of the total negatives). This allows the construction of corrected mf age-prevalence curves, which indicate that the observed prevalence may underestimate the true figures by between 25% and 100%. The age distribution of mf-negative individuals in the population is discussed in terms of current hypotheses about the interaction between disease and infection.

Adolescent↗

The relationship between the frequency distribution of Ascaris lumbricoides and the prevalence and intensity of infection in human communities.

Observed field data from a range of geographically distinct human communities suggest a consistent non-linear relationship between prevalence and mean intensity of Ascaris lumbricoides infection. Utilizing the negative binomial distribution as a description of observed aggregation, maximum-likelihood analysis reveals that the degree of aggregation is a negative linear function of mean worm burden. The factors responsible for this relationship in human populations require further study but may involve some combination of (i) density-dependent reduction in worm numbers within individuals, (ii) density-dependent parasite-induced host mortality or (iii) self-treatment by heavily infected hosts. Variability in the degree of aggregation appears dependent on the level of infection in a community and independent of geographical differences in the host or parasite populations.

Animals↗

Growth suppression in the Trichuris dysentery syndrome.

The Trichuris Dysentery Syndrome (Ramsey, 1962) is an insidious, chronic condition which has clinical features similar to Crohn's ileocolitis and ulcerative colitis, diseases similarly associated with growth retardation. The attained heights and weights of 19 children at the time of diagnosis of intens, -2.4 Standard Deviation (Z) scores from the Tanner-Whitehouse median with weight, adjusted for height-age, -1.3 Z. We present data on the growth velocities of 11 of the children in the half-year following worm expulsion by mebendazole. These children returned to their home environments without food supplementation or close follow-up, but showed an average height velocity of +5.5 Z and weight velocity (for height-age) of +2.4 Z. Of 8 children with unequivocal height spurts only 3 had any weight spurt. We suggest that the pattern of catch-up growth points to the existence of some specific link between allergy or inflammation in the lower intestinal tract and suppression of linear growth, rather than to stunting due to general deprivation and undernutrition.

Animals↗

Infectious disease and the Unesco basic education initiative.

As part of a Basic Education for All campaign, Unesco is exploring ways to improve health and nutrition in school-age children in order to help them take advantage of the only schooling they may ever receive. At the first international Unesco working meeting on health, nutrition and school performance, intestinal helminths were identified as more appropriate immediate targets than malaria and other infectious diseases. Prevalence and intensity of infection in school-age children, the schools as vehicles of intervention, and the availability of interventions contributed to this choice. However, there are still many gaps in our knowledge of the effects of infectious diseases in schoolchildren. Through the improvement of understanding in this area, the parasitology community may be able to contribute to the Unesco project.

Journal Article↗

Density dependence in establishment, growth and worm fecundity in intestinal helminthiasis: the population biology of Trichuris muris (Nematoda) infection in CBA/Ca mice.

The results are presented of an experimental study of the population biology of chronic Trichuris muris (Nematoda) infection in cortisone-treated CBA/Ca mice. Attention is focused upon both the validity of the common use of faecal egg counts to demonstrate density dependence in helminth fecundity, and the identification of other possible density-dependent mechanisms that may regulate worm numbers in chronic trichuriasis. The results show that faecal egg counts, although demonstrating high daily variation, are not an artefact of host faecal output but a significant density-dependent function of worm burden. This finding contrasts with the observations on Heligmosomoides polygyrus infection in outbred MFI mice, but accords with similar studies in a wide variety of host - helminth systems. Worm establishment in the murine host is found to be a density related function of infection dose. This is attributed to the probable existence of a physical gut-carrying capacity in the murine host for T. muris. Worm distribution in the gut is also shown to the density dependent, with worms being displaced from the caecum to the colon at increasing intensities of infection. The sex ratio of the adult parasites, however, is found to be both unitary and independent of worm burden. Evidence for a significant density-dependent decline in female T. muris growth or size is presented. The results also show a significant positive association between female T. muris weight and per capita fecundity. These findings indicate that the stunted growth of individual worms at high parasite densities may be a potential mechanism underlying density dependence in helminth fecundity.

Animals↗

Seroepidemiological study of the transmission of the mumps virus in St. Lucia, West Indies.

A seroepidemiological study of the prevalence of mumps virus specific antibodies reveals a pattern of endemic persistence on the island of St Lucia in the West Indies. In the unvaccinated population the proportion seropositive rose rapidly in the child age classes to attain a stable plateau close to unity in value in the teenage and adult age groups. The average age at infection was estimated to be between 3 and 4 years of age and the average duration of detectable levels of maternally derived antibodies was approximately 3 months. Analyses based on mathematical models of the transmission dynamics of the virus suggest that in excess of 75% of each cohort of 1- to 2-year-old children must be effectively immunized to eliminate mumps virus transmission. A mumps radial haemolysis test, developed for quantitative measurements of antibody, is discussed.

Adolescent↗

Population ecology of intestinal helminth infections in human communities.

The distribution of worm burdens in human populations is a major determinant of both the dynamics of transmission and the level of community morbidity. The distribution exhibits convexity with host age, which appears to correlate with exposure in the young age-classes but not in adults, and may be evidence for the development of an acquired immune response. The distribution between individuals is typically overdispersed. Individuals are predisposed to high (or low) intensity of infection and to a correspondingly high (or low) rate of acquisition of infection. A major epidemiological question is whether this reflects individual differences in environmental exposure or susceptibility. Environmental studies that have observed clustering of intense infection in particular households are supportive of either mechanism. Individual host behaviours that predispose to infection have an overdispersed distribution and may alone, or as compounding factors, generate the observed distribution of infection intensity. Factors such as host nutrition and physiology may modify host immune-responsiveness and hence susceptibility. Preliminary evidence suggests correlates between infection intensity and HLA class II antigens, and tentatively implies a genetic factor in susceptibility. These findings suggest that further understanding of the relative importance of environmental factors and resistance to the acquisition of intense infection is dependent upon a multidisciplinary approach to epidemiological field study.

Ecology↗

Clustering of Ascaris lumbricoides and Trichuris trichiura infections within households.

A survey of 428 households in a shanty town in Coatzacoalcos, Mexico, revealed high prevalences of Ascaris lumbricoides and Trichuris trichiura. The data were analysed separately for A. lumbricoides and T. trichiura in order to investigate the spatial distribution of heavy infections through the town. Within each age class, those individuals with egg counts in the upper 20% of the range for that age were classified as "heavily infected". When the data were stratified by household size, it was found that the distribution of "heavily-infected" individuals was not random in the community. "Heavily-infected" individuals were found together in households; fewer household units had a single heavily-infected individual than would be expected by chance. Such a pattern could result either from genetic similarities among family members influencing their ability to mount an effective immunological response to infection, or focal transmission in the vicinity of the home, or both. This result may have important implications for the development of community control programmes.

Adolescent↗

Age-related prevalence, intensity and frequency distribution of gastrointestinal helminth infection in urban slum children from Kuala Lumpur, Malaysia.

The gastrointestinal helminth infection status of 1574 children living in a slum area of Kuala Lumpur, Malaysia was assessed by quantitative coprology. Almost two-thirds were infected with Trichuris trichiura, 49.6% with Ascaris lumbricoides, and 5.3% with hookworm. Infection prevalence rose rapidly to a stable asymptote at 7 years of age, and the age-intensity profile was convex with maximal values in the 5-10 year age classes. This pattern was the same for males and females, but differed markedly between different ethnic groups. The frequency distributions of A. lumbricoides and T. trichiura were highly overdispersed (k values were 0.21 and 0.27, respectively), and age-dependent over the 0-8 year age classes. This suggests that the force of infection with these nematodes is lower in infants than in older children.

Adolescent↗

Quantitative assessment of geophagous behaviour as a potential source of exposure to geohelminth infection.

The most common form of pica, geophagy, has direct adverse nutritional effects and also exposes children to soil-borne infection. Existing methods for assessing geophagy are either inappropriate for field use (radiology) or unreliable (reporting). A new method is described, based on the measurement of soil-derived silica in stools. More than 90% of silica is excreted within one gut transit period of ingestion. The amount excreted is proportional to the amount ingested. Faecal levels of dietary silica (less than 2% dry wt stool) can be distinguished from levels due to geophagy (up to 25% dry wt stool). Studies in 2 children's homes in Jamaica showed that 33% and 66% of children were geophagous, ingesting up to 10 g soil day-1. The geophagy of less than 20% of the children accounted for greater than 60% of the total soil ingested. This overdispersion of exposure to soil-borne infection may contribute to the observed aggregation of geohelminth infection.

Child↗

Trichuris is not trivial.

There is no doubt that whipworm, Trichuris trichiura, is common - infecting up to 800 million people throughout tropical and temperate areas. Less clear has been its clinical significance, largely because of the chronic insidious nature of the disease. Here, Ed Cooper and Don Bundy discuss the scale of disease caused by Trichuris, pointing to possible reasons for its neglect- under-recognition, under-reporting, and/or uncertainty of pathogenesis.

Journal Article↗