Search PubMed⌕ Search

Biomedical subjects

D A Bundy

Publications and source records attributed to D A Bundy.

At least 37 records · Page 2Linked to original sources
PubMed1999

Parasitic infection with Trichuris trichiura influences plasma levels of soluble HLA class I.

High levels of sHLA-I (soluble HLA--class I) have been correlated with rejection episodes in solid organ transplant recipients and with graft versus host disease in bone marrow recipients. Studies of human infection with parasitic worms of the gut have suggested that certain individuals may be genetically predisposed to intense infection. In this study, the influence of parasitic helminth infection on levels of sHLA-I in plasma was investigated in 155 HLA typed individuals from St. Lucia, exposed to the gut parasite Trichuris trichiura. The results confirmed previous findings showing increased levels of sHLA-I in HLA-A9, and in this case HLA-A23 positive individuals. However, HLA-A9 positive individuals with high worm burden had significantly lower levels of sHLA-I in their plasma compared with HLA-A9 positive subjects with low worm burden. These results suggest that the intensity of T. trichiura infection influences the ability of HLA-A9 positive subjects to maintain high levels of sHLA-I.

Animals↗
PubMed1999

Planning chemotherapy based schistosomiasis control: validation of a mathematical model using data on Schistosoma haematobium from Pemba, Tanzania.

A mathematical model, based on a deterministic differential equation framework, has been developed to predict the impact of community chemotherapy programmes for human schistosomiasis. Here, this model is validated using data collected from a long-term control programme for urinary schistosomiasis on the island of Pemba, Zanzibar, United Republic of Tanzania, initiated in 1986 and still ongoing, in which schoolchildren were offered praziquantel chemotherapy every 6 months. Prevalence of infection and blood in urine were monitored in all the schools (total 26000 children from 60 schools) and more detailed data were collected in selected evaluation schools. Model predictions were run by using the initial prevalence as input. The predictions were very close to the observed decreases in prevalence and in prevalence of blood in urine. The correspondence improved further when the data were combined, going from single school level to district, and when the entire data set was combined. The accuracy of the predictions suggests that this model could be used as a tool to predict the consequences of chemotherapy control programmes. It is currently in press as a Windows software package under the name of 'EpiSchisto'.

Adolescent↗
PubMed1999

L3 antigen-specific antibody isotype responses in human strongyloidiasis: correlations with larval output.

Autoinfective strongyloidiasis is potentially fatal, yet the majority of infected individuals harbour asymptomatic and chronic infections. The role of humoral responses in modulating autoinfection was assessed by examining antibody isotype responses to filariform larval antigens amongst chronically infected ex-Far East Prisoners of War (exFEPOWs) with longstanding (> 30 years) infection. Serum immunoglobulin (Ig)G1, IgG4, IgE and IgA responses to whole Strongyloides stercoralis L3 extracts and their constituent antigenic components were characterized by ELISA and quantitative immunoblotting. Comparison of two groups of S. stercoralis infected exFEPOWs with and without detectable larvae in stool demonstrated novel trends. Significantly enhanced recognition of six immunodominant antigenic components by IgA was associated with undetectable larval output, as was enhanced IgE recognition of several components. Additionally, IgE and IgG4 exhibited parallel antigen recognition patterns. These findings are consistent with roles for IgA in modulating larval output, for IgE in regulating autoinfection, and for IgG4 in blocking IgE-mediated responses in human strongyloidiasis.

Animals↗
PubMed1999

Evidence for an association between hookworm infection and cognitive function in Indonesian school children.

The association between helminth infection and cognitive and motor function was investigated in school-age children in Java, Indonesia. 432 children from 42 primary schools participated in the study. Children were stratified by age and sex into two age groups, 8-9 years and 11-13 years. Children infected with hookworm performed significantly worse than children without hookworm infection in 6 of the 14 cognitive or motor tests. After controlling for school (as a random effect) plus age, socio-economic status and parental education, sex, stunting (height-for-age < - 2sd), body mass index, haemoglobin concentration and the presence of A. lumbricoides and T. trichiura infections, infection with hookworm explained significantly lower scores on tests of Fluency (P < 0.01), Digit-Span Forwards (P < 0.01), Number Choice (P < 0.01), Picture Search (P < 0.03), Stroop Colour Word (P < 0.02) and Mazes (P < 0.001). In 4 of the 6-tests (Fluency, Number Choice, Picture Search and Mazes), there was a significant interaction between hookworm infection and age (P < 0.03), indicating that the association between hookworm and lower test scores increased with age. No associations were observed between hookworm infection and scores in tests of Digit-Span Backwards, Corsi-Block, Stroop Colour, Stroop Interference, Free Recall, Verbal Analogies, Bead Threading or the Pegboard (P > 0.05). Tests associated with helminths represented various functions of working memory. No significant associations between helminth infection and motor function were observed that could not be explained by chance. The results suggest that hookworm infection can have a significant adverse effect on children's working memory which may have consequences for a child's reasoning ability and reading comprehension. Although the results are only associational, the fact that differences in cognition were observed at baseline imply that preventing infection with helminths in school-age children could be of benefit.

Adolescent↗
PubMed1999

The performance of school-based questionnaires of reported blood in urine in diagnosing Schistosoma haematobium infection: patterns by age and sex.

This study investigates the performance of school-based questionnaires of reported blood in urine as an indicator of the prevalence of Schistosoma haematobium infection in schools and the presence of infection in individuals. In most schools (87%), the prevalence of reported blood in urine underestimates the prevalence of S. haematobium infection. Predictive value analysis suggests that a threshold of 30% reported blood in urine would identify most of the high prevalence schools (i.e. those with 50% or more children infected with S. haematobium). Although the prevalence of S. haematobium infection was greater in males than females, girls reported a lower prevalence of blood in urine than boys even at comparable levels of infection. Reported blood in urine in females was more specific (identifying 10% more uninfected girls than the sign in boys), but was far less sensitive (identifying less than 20% of infected girls than boys). The sensitivity of reported blood in urine was also related to age, being significantly lower in girls over 14 years of age. The proportion of infected children who reported blood in urine was also lower in schools where the prevalence of reported blood in urine is less than 30%. The results suggest that the selective treatment of children based on reported blood in urine in low prevalence schools would miss a high proportion of infected children, particularly girls. It remains unclear whether other rapid assessment techniques, such as the use of reagent strips, would offer greater cost-effectiveness.

Adolescent↗
PubMed1999

The impact of population level deworming on the haemoglobin levels of schoolchildren in Tanga, Tanzania.

The impact of albendazole (400 mg) and praziquantel (40 mg/kg body weight) treatment of schoolchildren was compared with placebo according to the presence of anaemia (haemoglobin concentration < 11. 0 g/dl) and heavy (> 5000 epg) or light (< 5000 epg) hookworm egg load. The study was conducted in rural Tanga. Medication was administered in September 1994 and children were followed-up in January 1995. Overall, anthelminthic treatment reduced the fall in haemoglobin concentration compared with that observed in the placebo group (- 0.11 g/dl vs. - 0.35 g/dl; P = 0.02). Anthelminthic treatment was of greatest benefit to the 9% of children with both anaemia and heavy hookworm egg load (+ 0.67 g/dl vs. - 0.67 g/dl) and was also of significant benefit to the 38% of children with anaemia and light hookworm egg load (+ 0.07 g/dl vs. - 0.21 g/dl). It was of no significant benefit to children who were not anaemic. This study suggests that single-dose anthelminthic treatment distributed in schools in this area achieves haematological benefits in nearly half of children infected with S. haematobium and geohelminths (37% of total population).

Anemia↗
PubMed1999

Evidence for an improvement in cognitive function following treatment of Schistosoma japonicum infection in Chinese primary schoolchildren.

A double-blind, placebo-controlled, treatment trial was conducted in Sichuan, China to investigate the unique and combined effects on the cognitive function (working memory) of children after treating geohelminth infections with albendazole and treating Schistosoma japonicum infection with praziquantel. One hundred eighty-one children 5-16 years of age participated. At baseline, the praziquantel and placebo groups were similar in all background characteristics. Three months after praziquantel treatment, there was a significant reduction in the prevalence and intensity of S. japonicum infection. There were significant age group by praziquantel treatment interaction effects in three of the five cognitive tests, Fluency, Picture Search, and Free Recall, with effects being strongest in the youngest children (5-7 years old). Exploratory analysis within the youngest children showed a significant positive main effect of treatment on Fluency (P < 0.001), after controlling for sex, anthropometric, and parasitic and iron status. There was also a treatment by height-for-age interaction (P = 0.03) and a treatment by iron status interaction (P = 0.024) on Fluency. There was a treatment by S. japonicum intensity interaction (P < 0.001) on Free Recall, but the main effect of treatment on Picture Search was not significant (P = 0.058). Younger children and those who are physically the most vulnerable are likely to benefit the most from the treatment of S. japonicum infection in terms of improved performance on tests of working memory.

Adolescent↗
PubMed1998

Molecular and functional characterization of a recombinant protein of Trichuris trichiura.

The pore-forming protein of the human whipworm, Trichuris trichiura, has been postulated to facilitate invasion of the host gut and enable the parasite to maintain its syncytial environment. The data presented here describe the first, to our knowledge, molecular characterization of a pore-forming protein in any helminth and provide a unique demonstration of the functional interaction between a parasite antigen and host molecules. Immunological screening of a T. trichiura cDNA library with T. trichiura infection sera identified a clone of 1.4 kB, the cDNA consisting of 1495 base pairs encoding a protein of 50 kDa. The sequence has a highly repetitive nature containing nine four-disulphide-bonded core domains. Structural prediction analyses reveals an amphipathic nature. TT50 induced pore formation in bilayers in a manner identical to that of the native protein. IgG antibody isolated from T. trichiura infection serum was observed to abolish channel activity.

Amino Acid Sequence↗
PubMed1998

Herd immunity to filarial infection is a function of vector biting rate.

Despite the existence of an impressive body of work on human immune responses against filarial infections, the occurrence of a protective response to infection remains unclear. Here, we use a combined modelling and comparative data analysis framework to address this issue for human infections with the filarial parasite, Wuchereria bancrofti. By analogy with previous work, the analysis involves the comparison of observed field patterns of infection with epidemiological patterns predicted by a mathematical model of parasite immunity. Unlike most other human helminths, which are transmitted by ingestion or dermal penetration, exposure to infection with lymphatic filariasis can be measured explicitly in terms of vector mosquito biting rates, thereby also allowing, probably for the first time, examination of the suggested role of exposure in generating herd immunity to macroparasites. Observed field patterns in this study were derived from 19 different published studies, which gave parallel estimates of community exposure rates and the corresponding age--prevalence patterns of infection, while predictions of the epidemiological impact of herd immunity were obtained using a catalytic model framework. The results provide the first conclusive evidence to date that variations in the observed age--prevalence patterns of infection in filariasis can be effectively explained by the occurrence of an exposure-driven acquisition of herd immunity. We discuss this result in terms of implications for the new World Health Organization-led initiative for the global control of this parasitic disease.

Animals↗
PubMed1998

Modelling variability in lymphatic filariasis: macrofilarial dynamics in the Brugia pahangi--cat model.

A striking feature of lymphatic filariasis is the considerable heterogeneity in infection burden observed between hosts, which greatly complicates the analysis of the population dynamics of the disease. Here, we describe the first application of the moment closure equation approach to model the sources and the impact of this heterogeneity for macrofilarial population dynamics. The analysis is based on the closest laboratory equivalent of the life cycle and immunology of infection in humans--cats chronically infected with the filarial nematode Brugia pahangi. Two sets of long-term experiments are analysed: hosts given either single primary infections or given repeat infections. We begin by quantifying changes in the mean and aggregation of adult parasites (inversely measured by the negative binomial parameter, kappa in cohorts of hosts using generalized linear models. We then apply simple stochastic models to interpret observed patterns. The models and empirical data indicate that parasite aggregation tracks the decline in the mean burden with host age in primary infections. Conversely, in repeat infections, aggregation increases as the worm burden declines with experience of infection. The results show that the primary infection variability is consistent with heterogeneities in parasite survival between hosts. By contrast, the models indicate that the reduction in parasite variability with time in repeat infections is most likely due to the 'filtering' effect of a strong, acquired immune response, which gradually acts to remove the initial variability generated by heterogeneities in larval mortality. We discuss this result in terms of the homogenizing effect of host immunity-driven density-dependence on macrofilarial burden in older hosts.

Animals↗
PubMed1998

Associations among multiple geohelminth species infections in schoolchildren from Pemba Island.

In order to estimate the potential benefits of interventions against multiple geohelminth species in endemic areas, an improved understanding of the population biology of multiple infections is required. This paper presents a detailed analysis of the associations among Ascaris lumbricoides, Trichuris trichiura and hookworm infections in 1539 schoolchildren on Pemba Island, Tanzania, where 58% of the sampled children carried infections of all 3 parasites at the time of the study. Infection intensities of different species were positively correlated, and individuals with single-species infections had generally lower species-specific egg counts than individuals with multiple-species infections. There was no age- or sex-related clustering of infections. A weak clustering of intense infections among individuals with multiple-species infections was observed, which became more pronounced as the threshold defining an intense infection increased for each species. The results suggest that individuals with multiple species infections are likely to be at highest risk of geohelminth-related morbidity, not only because of the number of infections they harbour, but also because they generally carry heavier infections of each species.

Animals↗
PubMed1998

Antigenic variability in Trichuris trichiura populations.

The present study examines antigenic variability for the human whipworm Trichuris trichiura. Recognition by IgG of somatic antigens of individual worms collected from 3 intensely infected children from Jamaica, West Indies has been investigated by immunoblotting. When probed with 1 plasma sample, significant differences in recognition of 2 selected antigens among worm populations and between male and female worms was observed. In addition, there was evidence for antigenic variability within worm populations at the individual worm level. Such variation may have considerable implications for the development of immunity to parasitic nematodes.

Animals↗
PubMed1998

Epidemiology of soil-transmitted nematode infections in Ha Nam Province, Vietnam.

Baseline epidemiological data are presented from a parasitological survey conducted in Thuy Loi commune, Ha Nam province, Vietnam; a farming community where night soil is routinely used as fertilizer for crops. 177 households were visited and 543 individuals (aged 1-88 years) recruited to the study. Helminth infection intensity was assessed by Kato-Katz to determine the density of parasite eggs per gram of stool (epg). Ascaris lumbricoides, Trichuris trichiura and hookworm infections were the only species detected. 83% of individuals were infected with A. lumbricoides (mean epg = 11,971), 94% with T. trichiura (mean epg = 793) and 59% with hookworm (mean epg = 302). Age-dependent patterns of infection prevalence and intensity were similar for A. lumbricoides and T. trichiura, but markedly different for hookworm infection. Similarly, age-dependency in the k-values for the three infections was due to covariance with the respective mean intensities with age rather than to independent age effects, with similar patterns for A. lumbricoides and T. trichiura, and a different pattern for hookworm. Three major conclusions can be drawn from the multiple-species analyses: There is positive interaction between A. lumbricoides and T. trichiura infections; high-intensity A. lumbricoides infections are significantly associated with high-intensity T. trichiura infections; and there is positive interaction between these two species such that infection intensity of A. lumbricoides is higher in individuals with concurrent T. trichiura infection than in individuals without and vice versa.

Adolescent↗
PubMed1998

Can we deworm this wormy world?

While programmes such as the Rockefeller campaign were specifically targeted at a particular parasite species, the current trend is towards the simultaneous control of all the major geohelminth species. New, broad-spectrum, low-cost anthelmintics and new understanding of epidemiology have led to more cost-effective and sustainable strategies. The WHO, UNICEF and the World Bank all now support global and regional efforts to achieve control of morbidity from intestinal worms. In this paper, we aim to show what's new in clinical helminthology and what has brought about the great improvement in the success of the new approaches to control.

Adolescent↗
PubMed1998

Epifil: a dynamic model of infection and disease in lymphatic filariasis.

The lack of a quantitative framework that describes the dynamic relationships between infection and morbidity has constrained efforts aimed at the community-level control of lymphatic filariasis. In this paper, we describe the development and validation of EPIFIL, a dynamic model of filariasis infection intensity and chronic disease. Infection dynamics are modeled using the well established immigration-death formulation, incorporating the acquisition of immunity to infective larvae over time. The dynamics of disease (lymphodema and hydrocele) are modeled as a catalytic function of a variety of factors, including worm load and the impact of immunopathological responses. The model was parameterized using age-stratified data collected from a Bancroftian filariasis endemic area in Pondicherry in southern India. The fitted parameters suggest that a relatively simple model including only acquired immunity to infection and irreversible progression to disease can satisfactorily explain the observed infection and disease patterns. Disease progression is assumed to be a consequence of worm induced damage and to occur at a high rate for hydrocele and a low rate for lymphodema. This suggests that immunopathology involvement may not be a necessary component of observed age-disease profiles. These findings support a central role for worm burden in the initiation and progression of chronic filarial disease.

Adolescent↗
PubMed1997

Global mapping of lymphatic filariasis.

Disease maps are becoming increasingly important in infectious disease epidemiology and control. For lymphatic filariasis, the development of such maps has been hampered in the past by the lack of data on the geographical distribution of levels of infection or disease. Here, Edwin Michael and Don Bundy present an atlas for this parasitic disease derived from a recently compiled geographical database. Focusing on mapping and analysis of case prevalence data at the global and regional levels, the authors show how mapping the geographical distribution is integral not only to assessing spatial patterns in the infection and disease distribution but also to stratifying endemic areas by infection and/or disease rate.

Journal Article↗
PubMed1997

Human schistosomiasis: potential long-term consequences of vaccination programmes.

Fields trials of new schistosomiasis vaccines are anticipated within the next few years, but there remains great uncertainty regarding the optimal design of vaccination programmes. Mathematical models are used here to explore the potential long-term consequences of vaccination, assuming that the vaccines provide partial protection for a limited period. The analysis suggests that vaccines acting to reduce infection rates or egg output will have a similar impact on levels of infection, that this impact may be highly sensitive to the duration as well as the degree of protection, that it may take several decades for the full impact to become apparent, and that one consequence will be peak levels of infection occurring in older age classes. In terms of lowering levels of infection there may be advantages in delaying vaccination until children reach school age, especially if the vaccine gives short-lived protection, or to repeat vaccination. The short-term advantages can be greatly increased by combining the introduction of a vaccination programme with initial mass chemotherapy. Continuous combined vaccination and chemotherapy programmes may also be more effective than either intervention alone. More research is needed on the consequences of vaccinating previously vaccinated, infected, and infected and treated individuals and the importance of natural boosting of vaccine-induced immunity.

Adolescent↗