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Jeffrey Bethony

Publications and source records attributed to Jeffrey Bethony.

17 recordsLinked to original sources
PubMed2006

Contrasting patterns in the small-scale heterogeneity of human helminth infections in urban and rural environments in Brazil.

Marked heterogeneity exists in the patterns of parasitic infection between individuals, households and communities. Analysis of parasite distributions within populations is complicated by the fact that parasite distributions are highly aggregated and few studies have explicitly incorporated this distribution when investigating small-scale spatial heterogeneities. This study aimed to quantify the small-scale (within- and between-household) heterogeneity of helminth infection in an area of Minas Gerais State, Brazil, with rural and urban sectors. Parasitological data from a cross-sectional survey of 1,249 individuals aged 0-86 years from 242 households were analysed. Within-household clustering of infection was assessed using random effect logistic regression models and between-household spatial heterogeneity was assessed using a Bayesian negative binomial spatial model. The overall prevalence of hookworm (Necator americanus) was 66.9%, the prevalence of Schistosoma mansoni was 44.9% and the prevalence of Ascaris lumbricoides was 48.8%. Statistical analysis indicated significant (within) household and (between household) spatial clustering of hookworm in both rural and urban areas and of S. mansoni in rural areas. There was no evidence of either household or spatial clustering of S. mansoni in urban areas. The spatial correlation of S. mansoni was estimated to reduce by half over a distance of 700 m in the rural area. Rural hookworm had a much smaller half-distance (28 m) and urban hookworm showed an even smaller half-distance (12 m). We suggest that such species-specific differences in patterns of infection by environment are primarily due to variation in exposure and parasite life cycle, although host genetic factors cannot be ruled out.

Adolescent↗
PubMed2006

Soil-transmitted helminth infections: ascariasis, trichuriasis, and hookworm.

The three main soil-transmitted helminth infections, ascariasis, trichuriasis, and hookworm, are common clinical disorders in man. The gastrointestinal tract of a child living in poverty in a less developed country is likely to be parasitised with at least one, and in many cases all three soil-transmitted helminths, with resultant impairments in physical, intellectual, and cognitive development. The benzimidazole anthelmintics, mebendazole and albendazole, are commonly used to remove these infections. The use of these drugs is not limited to treatment of symptomatic soil-transmitted helminth infections, but also for large-scale prevention of morbidity in children living in endemic areas. As a result of data showing improvements in child health and education after deworming, and the burden of disease attributed to soil-transmitted helminths, the worldwide community is awakening to the importance of these infections. Concerns about the sustainability of periodic deworming with benzimidazole anthelmintics and the emergence of resistance have prompted efforts to develop and test new control tools.

Animals↗
PubMed2006

Hookworm vaccines: past, present, and future.

Hookworms are gastrointestinal nematodes that infect almost 1 billion people in developing countries. The main clinical symptom of human hookworm infections is iron-deficiency anaemia, a direct consequence of the intestinal blood loss resulting from the parasite's feeding behaviour. Although treatment is available and currently used for the periodic removal of adult hookworms from patients, this approach has not effectively controlled hookworm in areas of rural poverty. Furthermore, treated individuals remain susceptible to reinfection following exposure to third-stage infective hookworm larvae in the soil as early as 4-12 months after drug treatment. Therefore, a prophylactic vaccine against hookworm infection would provide an attractive additional tool for the public-health control of this disease. The feasibility of developing a vaccine is based on the previous success of an attenuated larval vaccine against canine hookworm. Several laboratory and field studies have explored the development of a human anti-hookworm vaccine, describing potential protective mechanisms and identifying candidate antigens, one of which is now in clinical trials. The current roadmap that investigators have conceived has been influenced by vaccine development for blood-feeding nematodes of livestock and companion animals; however, recombinant vaccines have yet to be developed for nematodes that parasitise animals or human beings. The roadmap also addresses the obstacles facing development of a vaccine for developing countries, where there is no commercial market.

Global Health↗
PubMed2005

Antibodies against a secreted protein from hookworm larvae reduce the intensity of hookworm infection in humans and vaccinated laboratory animals.

The development of a vaccine would provide an important new tool for the control of human hookworm infection. On the basis of successful vaccination of laboratory animals with living irradiated, third-stage hookworm larvae (L3), we examined the antibody responses of individuals from hookworm endemic areas of Brazil and China against the most abundant L3 secreted antigens, the ancylostoma secreted proteins, ASP-1 and ASP-2. Logistic regression was used to investigate the effects of antibody isotype responses to ASPs on the risk of an individual harboring heavy hookworm infection. A significant protective association was observed between increasing anti-ASP-2 IgE levels and the risk of heavy hookworm infection. To confirm that ASP-2 is a protective antigen, laboratory dogs were immunized with recombinant ASP-2 formulated with the GlaxoSmithKline Adjuvant, AS03. Sera obtained from the immunized dogs exhibited high geometric mean antibody titers, immunoprecipitated native ASP-2 from L3 extracts and localized the site of ASP-2 expression to the glandular esophagus and body channels exiting to the cuticle. The sera also exhibited an increased ability to inhibit migration of L3 through tissue in vitro relative to sera from AS03-injected controls. Upon L3 challenge, the ASP-2 vaccinated dogs exhibited significant reductions in fecal egg counts and intestinal hookworm burden. These findings provide strong support for the development of an effective recombinant vaccine against hookworm infection in humans.

Adolescent↗
PubMed2005

Immunogenicity of the hookworm Na-ASP-2 vaccine candidate: characterization of humoral and cellular responses after vaccination in the Sprague Dawley rat.

The recombinant larval protein Na-ASP-2 from the human helminth parasite Necator americanus is a lead candidate for a human hookworm vaccine. We have characterized the humoral and cellular immune responses elicited by the Na-ASP-2 formulated with the aluminum-based adjuvant Alhydrogel in the Sprague Dawley rat. We demonstrated that Na-ASP-2 vaccine induced a strong antibody response at all doses tested, as evidenced by high specific IgG1, IgG2a and IgM titers. High IgG antibody titers were maintained up to three months post vaccination and were boosted by an additional vaccine dose. Specific cell proliferation and a Th2 cytokine profile were also observed in peripheral blood of all rats immunized with the formulated vaccine. Host IL-6 levels were also significantly elevated. These data provide evidence that the immune response of the Na-ASP-2 vaccine is robust and durable and therefore suitable for the further clinical development of the Na-ASP-2 vaccine.

Adjuvants, Immunologic↗
PubMed2005

Comparative clinical and ultrasound study of egg-negative and egg-positive individuals from Schistosoma mansoni low morbidity endemic areas, and hospitalized patients with hepatosplenic disease.

Two hundred and twenty three subjects from a Schistosoma mansoni low morbidity endemic area and nine hospitalized hepatosplenic patients were submitted to stool test and clinical examination and abdomen ultrasound assessments. According to stool examination and ultrasound results, they were grouped as follows: G1 -- 63 Schistosoma mansoni egg-negative individuals; G2 -- 141 egg-positive patients and without evidence of periportal fibrosis; G3 -- 19 egg-positive patients with periportal echogenicity (3-6 mm); and G4 -- 9 hepatosplenic patients with periportal echogenicity (> 6 mm). Hepatomegaly detected by physical examination of the abdomen evaluated in the midclavicular line was verified in G1, G2 and G3, respectively, in 11.1, 12.1 and 26.3%. In G1, G2 and G3, periportal thickening occurred only in schistosomal patients (8.5%). Mild pathological alterations in patients that cannot yet be detected by clinical examination were detectable in the liver by ultrasound and can be due to fibrosis. The degree of mild periportal fibrosis was diminished in 57.9% of patients 12 months after treatment of schistosomiasis with oxamniquine. At ultrasonography, the mean liver left lobe measurement of G3 was larger than that of G1, and that of G4 larger than that of G1 and G2. The mean size of the spleen of G4 was significantly larger than that of the other three groups, and that of G3 larger than that of G1 and G2.

Adolescent↗
PubMed2004

A multihousehold study reveals a positive correlation between age, severity of ocular toxoplasmosis, and levels of glycoinositolphospholipid-specific immunoglobulin A.

A cross-sectional household study involving 499 individuals was undertaken in an area of Minas Gerais state, Brazil, where infection with Toxoplasma gondii is endemic. Nearly 50% (n=247) of the sample had T. gondii-specific antibodies, even individuals in the 5-9-year-old age group. Approximately 12.5% (n=28) of a random subsample of participants who were positive for T. gondii antibodies had ocular lesions associated with T. gondii infection. The frequency of ocular toxoplasmosis increased significantly with age, with approximately 50% of individuals >60 years of age having lesions. The size of the ocular lesion correlated positively (r=0.85; P=.01) with the serum level of immunoglobulin A specific for tachyzoite-derived glycoinositolphospholipids. We found that sharing the same residence accounted for 30% of the variation in infectivity among residents in the sample, whereas age was the main risk factor for development of ocular toxoplasmosis in patients who were positive for T. gondii antibodies.

Adolescent↗
PubMed2004

Human schistosomiasis mansoni: intensity of infection differentially affects the production of interleukin-10, interferon-gamma and interleukin-13 by soluble egg antigen or adult worm antigen stimulated cultures.

The effect of the intensity of infection (eggs per gram faeces, epg) on the production of interferon-gamma (INF-gamma), interleukin (IL)-10 and IL-13 by peripheral blood mononuclear cells (PBMCs) from individuals living in a Schistosoma mansoni-endemic area was evaluated. In vitro stimulation of PBMCs with soluble egg antigen (SEA) resulted in significantly higher secretion levels of IFN-gamma in egg-negative individuals compared with those with an intensity of infection of more than 100 epg. In contrast, the egg-positive group produced significantly higher amounts of IL-10. Levels of IL-13 did not differ significantly between egg-positive and egg-negative groups. These findings suggest that IL-10 is an important cytokine in the control of the T helper cell (Th) type 1 responses during human S. mansoni infection, shifting the immune response from Th0 in egg-negative individuals from an endemic area to a Th2 polarization in chronic infected individuals.

Adult↗
PubMed2004

Human hookworm infection in the 21st century.

The scientific study of human hookworm infection began at the dawn of the twentieth century. In recent years, there have been dramatic improvements in our understanding of many aspects of this globally widespread parasite. This chapter reviews recent advances in our understanding in the biology, immunology, epidemiology, public health significance and control of hookworm, and to look forward to the study of this important parasite in the 21st century. Advances in molecular biology has lead to the identification of a variety of new molecules from hookworms, which have importance either in the molecular pathogenesis of hookworm infection or in the host-parasite relationship; some are also promising vaccine targets. At present, relatively little is known about the immune responses to hookworm infection, although it has recently been speculated that hookworm and other helminths may modulate specific immune responses to other pathogens and vaccines. Our epidemiological understanding of hookworm has improved through the development of mathematical models of transmission dynamics, which coupled with decades of field research across multiple epidemiological settings, have shown that certain population characteristics can now be recognised as common to the epidemiology, population biology and control of hookworm and other helminth species. Recent recognition of the subtle, but significant, impact of hookworm on health and education, together with the simplicity, safety, low cost and efficacy of chemotherapy has spurred international efforts to control the morbidity due to infection. Large-scale treatment programmes are currently underway, ideally supported by health education and integrated with the provision of improved water and sanitation. There are also on-going efforts to develop novel anthelmintic drugs and anti-hookworm vaccines.

Ancylostomatoidea↗
PubMed2004

Exposure to Schistosoma mansoni infection in a rural area in Brazil. Part III: household aggregation of water-contact behaviour.

Much research points to the importance of the household in the study of water-borne diseases such as schistosomiasis. An important aspect of the household is the clustering of domestic activities associated with water collection, storage and usage. Such activities can result in the sharing of water-contact sites and water-contact behaviour, which expose household members to similar risks of infection. In previous studies, we determined that shared residence accounted for 28% of the variance in Schistosoma faecal egg excretion rates. We now quantify the effect of shared residence on the variation in water-related health behaviours. We found that shared residence accounted for 30% of the variation in total water contacts per week. It also accounted for a large proportion of the variation in individual water-contact behaviour: e.g. agricultural contacts (63%), washing limbs (56%) or bathing (41%). These results implicate the household as an important composite measure of the complex relationships between socioeconomic, environmental and behavioural factors that influence water-contact behaviour and, therefore, the transmission of schistosomiasis. Our results also support a focus on the household in the implementation of schistosomiasis prevention and control efforts.

Activities of Daily Living↗
PubMed2003

Transmission of Helicobacter pylori infection in families of preschool-aged children from Minas Gerais, Brazil.

We evaluated the role of the family in the transmission of Helicobacter pylori infection in preschool-aged children from a rural district in the State of Minas Gerais, Brazil. Sixty-six families (66 index children, 63 mothers, 60 fathers and 134 siblings), defined as at least one parent living in the same household with at least one offspring up to 8 years old, were studied. Odds ratios (OR) and 95% confidence intervals (CI) were estimated by logistic regression controlling for age, gender, number of children in household and H. pylori status of the father, mother and siblings. The prevalence of the infection was 69.7% (469 of 673) and it increased with age (P < 0.001). Positive mothers were a strong and independent risk factor for infection (OR 22.70; 95% CI 2.31-223.21). Positive siblings were also positively associated with infection (OR 1.81; 95% CI 1.01-3.30).

Adolescent↗
PubMed2003

Effect of vaccination with a recombinant fusion protein encoding an astacinlike metalloprotease (MTP-1) secreted by host-stimulated Ancylostoma caninum third-stage infective larvae.

Laboratory dogs were vaccinated intramuscularly with a recombinant fusion protein (expressed and isolated from Escherichia coli) formulated with the Glaxo SmithKline Adjuvant System 02 (AS02). The fusion protein encoded Ac-MTP-1, a developmentally regulated astacinlike metalloprotease secreted by host-stimulated Ancylostoma caninum third-stage larvae (L3). Control dogs were injected intramuscularly with an equivalent amount of AS02 adjuvant alone. The vaccinated and control dogs were then challenged by s.c. injection of 500 L3 of the canine hookworm A. caninum. The vaccinated dogs developed prechallenge immunoglobulin G2 (IgG2) antibody responses specific to anti-Ac-MTP-1-fusion protein with titers ranging between 1:40,000 and 1:364,000, whereas they developed antigen-specific immunoglobulin E antibody responses with titers ranging between 1:500 and 1:1,500. By immunoblotting, canine sera obtained from the vaccinated dogs recognized a protein of the estimated apparent molecular weight of Ac-MTP-1 in activated L3 secretory products. Spearman rank order correlations between the canine intestinal adult hookworm burden and quantitative egg counts at necropsy and anti-Ac-MTP-1 IgG2 antibody titers revealed a statistically significant inverse association (r = -0.89; P = 0.04), suggesting that this molecule offers promise as a recombinant vaccine.

Adjuvants, Immunologic↗
PubMed2002

Emerging patterns of hookworm infection: influence of aging on the intensity of Necator infection in Hainan Province, People's Republic of China.

We examined risk factors associated with Necator americanus infection among persons aged > or =50 years in Hainan Province, People's Republic of China. Age and sex made the most important contributions to the variation in infection intensity (28%-30%), with age alone responsible for 27% of this variation. When stratified by 20-year age intervals, the influence of shared residence was 23% for persons aged > or =50 years and 27% for those aged <20 years, who had the highest and lowest levels of infection intensity, respectively. This points to shared residence as a means of capturing the complex relationship between aging and shared socioeconomic, environmental, and behavioral factors that influence transmission of Necator infection. None of the other 26 personal or 32 household risk factors were found to be significant. The importance of aging in Necator infection reveals an emerging public health problem among the elderly population of developing countries.

Adolescent↗
PubMed2002

Effect of vaccinations with recombinant fusion proteins on Ancylostoma caninum habitat selection in the canine intestine.

Laboratory dogs were vaccinated subcutaneously with 3 different recombinant fusion proteins, each precipitated with alum or calcium phosphate. The vaccinated dogs were then challenged orally with 400 third-stage infective larvae (L3) of the canine hookworm, Ancylostoma caninum. The 3 A. caninum antigens selected were Ac-TMP, an adult-specific secreted tissue inhibitor of metalloproteases; Ac-AP, an adult-specific secreted factor Xa serine protease inhibitor anticoagulant; and Ac-ARR-1, a cathepsin D-like aspartic protease. Each of the 3 groups comprised 6 male beagles (8 +/- 1 wk of age). A fourth group comprised control dogs injected with alum. All of the dogs vaccinated with Ac-TMP or Ac-APR-1 exhibited a vigorous antigen-specific antibody response, whereas only a single dog vaccinated with Ac-AP developed an antibody response. Dogs with circulating antibody responses exhibited 4.5-18% reduction in the numbers of adult hookworms recovered from the small intestines at necropsy, relative to alum-injected dogs. In contrast, there was a concomitant increase in the number of adult hookworms recovered from the colon. The increase in colonic hookworms was as high as 500%, relative to alum-injected dogs. Female adult hookworms were more likely to migrate into the colon than were males. Anti-enzyme and anti-enzyme inhibitor antibodies correlated with an alteration in adult hookworm habitat selection in the canine gastroinntestinal tract.

Ancylostoma↗
PubMed2002

High levels of IgG4 to Schistosoma mansoni egg antigens in individuals with periportal fibrosis.

Specific IgG4 and IgE responses to adult worm antigen and soluble egg antigen (SEA) were examined in 267 individuals from an area in which schistosomiasis mansoni is endemic. Based on information obtained from clinical and sonographic examinations of this sample, the individuals were divided in three groups: 1) 204 individuals without periportal fibrosis, and liver and spleen enlargements; 2) 41 individuals without periportal fibrosis, but presenting with organopathy, with or without organomegaly; and 3) 22 individuals with periportal fibrosis, regardless of their status as having hepatomegaly and/or splenomegaly. Levels of IgG4 to SEA were significantly higher in sera from patients with fibrosis compared with the patients from the other two groups. We also found significantly higher levels of IgG4 against SEA in egg-negative patients with fibrosis compared with egg-negative patients from the other two groups. This report demonstrates a specific humoral response in patients presenting with initial fibrosis, a form of schistosomiasis transient between intestinal and severe hepatosplenic.

Abdomen↗
PubMedDate not supplied

Cellular responses and cytokine profiles in Ascaris lumbricoides and Trichuris trichiura infected patients.

The impact of intestinal helminth infection, i.e. Ascaris lumbricoides and Trichuris trichiura, on cellular responsiveness and cytokine production was investigated in young adults. Ascaris-specific cellular responsiveness was higher in parasite-free endemic controls than in patients infected with T. trichiura, or A. lumbricoides, or patients co-infected with both parasites. Also, mitogen-induced tumour necrosis factor (TNF)-alpha, interleukin (IL)-12 and interferon (IFN)-gamma secretion by peripheral blood mononuclear cells (PBMC) was higher in negative endemic controls than in infected individuals. Ascaris antigen-specific production of TNF-alpha, IL-12 and IFN-gamma was low in singly Ascaris as well as in co-infected patients, whereas secretion of IL-10 and IL-13 was elevated and similarly high in all patient groups. The detection of Trichuris-specific and Ascaris-specific IgG4 revealed significantly higher serum antibody levels in Trichuris or Ascaris patients when compared to endemic controls (P < 0.05), whereas parasite-specific IgE antibody levels were similarly high in infected individuals and in endemic controls. In summary, chronically infected Ascaris and Trichuris patients with a high parasite load presented reduced cellular reactivity and lower type 1 TNF-alpha, IFN-gamma and IL-12 responses when compared with endemic controls, whereas type 2 IL-10 and IL-13 productions were similar in all groups from the endemic area. The former may support parasite persistence, whereas substantial type 2 cytokine release may promote protective immunity, suggesting an adaptation of the host to control the parasite burden while minimizing immune-mediated host self-damage.

Adult↗