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J Bethony

Publications and source records attributed to J Bethony.

12 recordsLinked to original sources

Comparative immunology of human and animal models of hookworm infection.

Hookworm infection is a major cause of disease burden for animals and humans. Over the past years, the use of animal models in hookworm infections has been driven by the search of new anthelminthic therapies and, especially, vaccine development. These studies also contributed to the advance of knowledge on immunity to hookworms, offering new insights to understand the nature of this parasitic infection. In this article, we will summarize the essential features of the immune response in the two major animal models of hookworm infections (dog and hamster) and then consider its implication for the human immune response.

Ancylostoma↗

Production of interferon-gamma by natural killer cells and aging in chronic human schistosomiasis.

BACKGROUND: Aging is associated with several alterations in the phenotype, repertoire and activation status of lymphocytes as well as in the cytokine profile produced by these cells. As a lifelong condition, chronic parasitic diseases such as human schistosomiasis overlaps with the aging process and no systematic study has yet addressed the changes in immune response during infection with Schistosoma mansoni in older individuals. AIM: Herein we study the influence of immunological alterations brought about by senescence in the course of schistosomiasis. MATERIALS AND METHODS: Individuals 10-95 years of age, from both sexes, from an endemic area for S. mansoni infection were matched by intensity of infection as measured by egg counts. We analyzed, as a parameter, cytokine expression by lymphocytes and natural killer cells after in vitro stimulation with soluble egg antigen and soluble worm antigen using flow cytometry. RESULTS: We demonstrated that the frequency of CD16+ interferon-gamma (IFN-gamma)+ natural killer cells in negative individuals over the age of 70 years is significantly higher than in positive individuals after in vitro stimulation with S. mansoni antigen extracts. The frequency of these cells is increased in all individuals over the age of 50 years and only declines in positive individuals after 70 years of age. Analysis of either CD4? or CD8? cells after antigen stimulation show no significant increase in frequency of IFN-gamma in negative or in positive individuals of this age group, suggesting that the effect on CD16+ cells is not T-cell dependent. CONCLUSION: Since production of IFN-gamma has been related to resistance to schistosome infection, our data suggest that age-associated changes in CD16+ cells may play a role in controlling infection intensity in the elderly in S. mansoni endemic areas of Brazil.

Adolescent↗

Cellular responses and cytokine production in post-treatment hookworm patients from an endemic area in Brazil.

Human hookworm infections are distributed widely in tropical areas and have a significant impact on host morbidity and human health. In the present study, we investigated the cellular responsiveness and cytokine production in peripheral blood mononuclear cells (PBMC) from Necator americanus-infected schoolchildren who had recently received chemotherapy, and compared them with non-infected endemic controls. Hookworm patients and treated, egg-negative individuals showed a lower cellular reactivity against phytohaemagglutinin (PHA) and hookworm antigen when compared with egg-negative endemic controls. The baseline production of proinflammatory tumour necrosis factor-alpha (TNF-alpha) in PBMC from infected patients and treated, egg-negative individuals was elevated. On the other hand, PHA- or hookworm antigen-induced interleukin (IL)-12 and interferon (IFN)-gamma secretion was higher in endemic controls than in hookworm patients, who either continued egg-positive or were egg-negative after treatment. Also, PBMC from endemic controls secreted more IL-5 and IL-13 than the other patient groups. Opposite to that, the spontaneous as well as the antigen-driven IL-10 secretion was lower in endemic controls when compared with the other groups. In summary, patently hookworm-infected as well as egg-negative treated patients disclosed an elevated spontaneous cellular secretion of proinflammatory TNF-alpha, a prominent secretion of regulatory Th2-type IL-10 and an impaired production of IL-12, IFN-gamma, IL-5 and IL-13.

Albendazole↗

Additive host genetic factors influence fecal egg excretion rates during Schistosoma mansoni infection in a rural area in Brazil.

This study quantifies the influence of shared household and kinship on egg counts during Schistosoma mansoni infection in a sample from rural Brazil. Detailed genealogic information allowed assignment of 597 individuals to 6 multihousehold pedigrees residing in 145 households. A variance component method was used to partition egg counts into shared household, additive genetic, and individual-specific environmental effects. Host additive genetic effects consistently accounted for a large proportion of the variation in egg counts: 43% in an unadjusted model and 40% in model adjusted for covariates. In a model that examined the confounding of shared household with kinship, additive genetic effects still accounted for 27% of the variation in egg counts and shared household only 12%. The consistently important role for host additive genetic factors on the variation in egg counts points to new ways of modeling and understanding the mechanisms that contribute to trait variation during infection with S. mansoni.

Animals↗

Genetic analysis of quantitative traits in highly ascertained samples: total serum IgE in families with asthma.

The objective of this study was to compare the effect of an approximate ascertainment correction using proband phenotypes with heuristic corrections based on sample trait means and on published "standard" population values. Data were from the Collaborative Study on the Genetics of Asthma, which comprises 225 families ascertained through sib pairs affected with asthma. In variance component linkage analysis of IgE no lod scores greater than 3.0 were observed, either with or without several attempted corrections for ascertainment. The ascertained nature of the sample may have compromised the power to detect linkage to a quantitative trait (IgE) associated with the focal phenotype (asthma).

Adult↗

Exposure to Schistosoma mansoni infection in a rural area of Brazil. I: water contact.

The study of water contact patterns in rural Brazil presents unique challenges due to widely dispersed settlement patterns, the ubiquity of water contact sites, and the privatization of water resources. This study addresses these challenges by comparing the two most widely used methods of assessing water contact behaviour: direct observation and survey. The results of a 7-day direct observation of water contact were compared with water contact surveys administered 1 week after and then 1 year after the direct observation study. The direct observation study recorded a water contact rate higher than reported by other investigators (3.2 contacts per person per day); however, 75% of these contacts were for females and consisted mainly of domestic activities occurring around the household. A comparison of the frequency of water contact activities between the direct observation and the two surveys revealed several important points. First, no significant differences were found between methods for routine water contact activities (e.g. bathing), indicating that participants were able to accurately self-report some types of water contact activities. Second, significant differences were found in the recording of water contact activities that took place outside the observation area, indicating that direct observation may under-report water contact activities in areas where contact sites are dispersed widely. Third, significant differences between the direct observation and the survey method were more common for males than for females, indicating that the combination of widespread water contact sites and gender-specific division of labour may result in under-reporting of male contacts by direct observation methods. In short, despite the limitations in the recording of duration and body exposure, the survey method may more accurately record the frequency of water contact activities than direct observation methods in areas of widely dispersed water contact sites. Hence, surveys may be more suitable for the unique challenges of water contact in rural areas of Brazil.

Adolescent↗

Exposure to Schistosoma mansoni infection in a rural area in Brazil. II: household risk factors.

A number of studies have pointed out the potential importance of the household in the transmission of schistosomiasis. The clustering of domestic activities associated with water collection, storage, and usage can result in the sharing of transmission sites and infective water contact behaviours. In this study, we employed a variance component method to estimate effects due to individual risk factors and shared residence on the variance in faecal egg counts during Schistosoma mansoni infection. A suite of covariates, which included demographic, socioeconomic, water supply, and water contact behaviour terms, contributed 15% to the variance in faecal egg counts. Shared residence alone accounted for 28% of the variance in faecal egg excretion. When both the suite of covariates and shared residence were considered in the same model, shared residence still contributed 22% to the variance in infection intensity. These results point to the importance of shared residence as a means of capturing the complex interrelationship between shared demographic, socioeconomic, physical environmental, and behavioural factors that influence transmission of schistosomiasis at the household level.

Adolescent↗

Genetic epidemiology of fecal egg excretion during Schistosoma mansoni infection in an endemic area in Minas Gerais, Brazil.

There is considerable variation in the level of fecal egg excretion during Schistosoma mansoni infections. Within a single endemic area, the distribution of egg counts is typically overdispersed, with the majority of eggs excreted coming from a minority of residents. The purpose of this study was to quantify the influence of genetic factors on patterns of fecal egg excretion in a rural study sample in Brazil. Individual fecal egg excretions, expressed in eggs per gram of feces, were determined by the Kato-Katz method on stool samples collected on three different days. Detailed genealogic information was gathered at the time of sampling, which allowed assignment of 461 individuals to 14 pedigrees containing between 3 and 422 individuals. Using a maximum likelihood variance decomposition approach, we performed quantitative genetic analyses to determine if genetic factors could partially account for the observed pattern of fecal egg excretion. The quantitative genetic analysis indicated that between 21-37% of the variation in S. mansoni egg counts was attributable to additive genetic factors and that shared environment, as assessed by common household, accounted for a further 12-21% of the observed variation. A maximum likelihood heritability (h2) estimate of 0.44 +/- 0.14 (mean +/- SE) was found for the 9,604 second- and higher-degree pairwise relationships in the study sample, which is consistent with the upper limit (37%) of the genetic factor determined in the variance decomposition analysis. These analyses point to the significant influence of additive host genes on the pattern of S. mansoni fecal egg excretion in this endemic area.

Adolescent↗

The distribution of Biomphalaria spp. in different habitats in relation to physical, biological, water contact and cognitive factors in a rural area in Minas Gerais, Brazil.

A total of 256 sites in 11 habitats were surveyed for Biomphalaria in Melquiades rural area (State of Minas Gerais) in August and November 1999 and in March 2000. Of the 1,780 Biomphalaria collected, 1,721 (96.7%) were B. glabrata and 59 (3.3%) B. straminea. Snails were found in all habitats except in wells, with the largest mean numbers in tanks, seepage ponds and canals, and the smallest numbers in springs, rice fields and fishponds. People's knowledge of the occurrence of Biomphalaria at the collection sites and the presence of Biomphalaria ova were strongly correlated with the occurrence of snails, and distance between houses and collection sites, as well as water velocity were inversely correlated with Biomphalaria occurrence (p < 0.001). The strongest predictor o f Biomphalaria occurrence was the presence of tilapia fish in fishponds. Fourteen Biomphalaria (0.8% of all snails) found at 6 sites were infected with Schistosoma mansoni. Suggestions are made for the utilization of local people's knowledge in snail surveys and further studies are recommended on the possible use of tilapia for biological control of Biomphalaria in fishponds, as well as modeling of S. mansoni transmission and reinfection.

Animals↗

Familial resemblance in humoral immune response to defined and crude Schistosoma mansoni antigens in an endemic area in Brazil.

This study addressed whether the humoral immune response to crude and defined Schistosoma mansoni antigens aggregates within families. The sample included 155 siblings from 42 nuclear families in Brazil. Sera examined by ELISA for antibody isotypes reactive to defined schistosome antigens and crude schistosome antigens (soluble adult worm antigen preparation and soluble egg antigen) demonstrated that there was a difference in sibling-pair correlations between defined and crude S. mansoni antigens. In contrast to the finding with crude antigens, egg-positive sibling pairs showed significant familial resemblance for all IgG subclasses and IgE to adult-stage antigens Smp20.8 and Smp50. Only the IgE and IgG4 isotypes showed familial resemblance to the egg-stage antigen, Smp40. Egg-negative sibling pairs showed significant familial resemblance only for IgE and IgG4 to Smp40. That both the IgE and IgG4 response to defined S. mansoni antigens showed familial resemblance is interesting in light of the converging evidence for the role of IgE and IgG4 in human susceptibility and resistance to reinfection.

Adolescent↗

The immunoepidemiology of human hookworm infection.

Advances in hookworm immunoepidemiology are reviewed. Recent studies demonstrate a mixed Th1/Th2 response in human hookworm infection, with immunosuppression of specific and nonspecific IFN-gamma responses. There is increasing evidence for protective immunity in human hookworm infection, including anti-larval IL-5- and IgE-dependent mechanisms, and for immunological interactions between hookworm infection and other diseases.

Ancylostoma↗