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Effect of age and helminthic infection on IgE levels in slum children.

Helminthic infections can cause an IL-4-dependent polyclonal synthesis of IgE, which is the major cause of the elevated serum levels of this immunoglobulin in tropical populations. In the present study, we measured the IgE levels in the serum of children of different ages in slum areas of Caracas, Venezuela, where intestinal helminths are endemic. As would be expected, in children over 5 years of age, the IgE levels were highly elevated, and in addition, the cord blood serum levels were higher than those reported for populations where parasitic infections are uncommon. However, the IgE levels measured in the sera of children under 5 years of age were relatively low, and within the generally accepted normal ranges. This was surprising because the latter children were infected by parasites and had high IgG antibody levels against helminths. We found, however, that whereas older children had detectable IL-4 levels in their sera, the younger children did not. These results suggest that, despite infection of these slum children by common intestinal helminths, a polyclonal stimulation of IgE synthesis did not occur, possibly due to a lack of IL-4 production by an immature immune system.

Adolescent↗

Helminth infections and allergic diseases: from the Th2 paradigm to regulatory networks.

Both helminth infections and allergic diseases are characterized by a Th2 response. The former mostly affects developing countries while the later is steadily increasing in westernized countries, since most parasitic diseases have been eradicated. However, besides the cytokine pattern, both pathologies display striking similarities regarding the cell types involved in the process, the mucosal component of the inflammatory reaction and the immunoglobulin isotypes produced, IgE and IgA. Recent advances also suggest that allergic pathologies and some other inflammatory diseases arise from a similar dysfunction of the regulatory mechanisms, existing within the immune system. Such a dysregulation leads to a rupture of tolerance towards allergen. Chronic and moderate helminth infections might be beneficial to the induction of various regulatory mechanisms, involving specific regulatory cell populations (dendritic cells and lymphocytes), inhibitory receptors, blocking antibodies and two prominent cytokines: IL-10 and TGF-b, which would decrease the incidence of allergic diseases. This mechanism could provide a new vision of the so-called "hygiene hypothesis".

Animals↗

Cutaneous manifestations of intestinal helminthic infections.

Several intestinal helminths may involve the skin. In cutaneous larva migrans and enterobiasis this is often the only organ involved, whereas hookworm and trichinosis are characterized by multisystem disease. The clinical spectrum of strongyloidiasis may range from a low-grade chronic dermatitis to a fulminant, often fatal, hyperinfection syndrome in the immunocompromised host. In the absence of recent breakthroughs in diagnostic testing, a meticulous history and knowledge of the life cycles and the often characteristic skin manifestations of these parasites remain essential to prompt diagnosis and effective treatment.

Antiparasitic Agents↗

[Organ pathology in chronic tissue-dwelling helminthic infections: role of blood and tissue eosinophilia, immunoglobulinemia E, G4, and immune response-inducing factors].

The results of earlier clinical, pathomorphological, and immunological studies of organic visceral and tissue lesions in helminthic infections [2, 3, 8, 10, 11, 14, 46] and present clinical and immunological ones [4-6, 44, 45] were analyzed and discussed in the light of a fundamental literature data review. The chronic visceral pathology in tissue-dwelling helminthic infections is associated with super- and reinfections [1, 2, 16, 36], with an inadequate immune response of humans to the invasion of zoonotic agents [2, 6, 13, 20] and with an individual invalidity of an immune response to infections [1, 2, 6, 16, 54]. The persistent course of infections, especially zoonotic, leads to organic pathology, sometimes irreversible [2, 13, 15, 21, 34, 46] if an individual (population) does not respond by immunity or by acquired (inherited) tolerance of invasion [1, 2, 3, 11, 16, 20, 36]. Transplacental transfer of Opisthorchis felineus antigens in the hyperendemic foci of the infection does not prevent superinfections, but does prevent the acute phase of disease and significantly mitigates the organic lesions in the chronic phase in spite of a very high intensity of infection [7, 10, 11]. Paramyosines (Pmes), proteins expressed on the tegument of Schistosoma mansoni and S. japonicum, show their immunogenic effect [42]. Antibodies to PM of Lumbricoidea and to a cardiac muscle myosin peptide (alpha-mp), known to induce experimental allergic myosites [55], were revealed in the sera of 32 trichinellosis, toxocarosis, opisthorchiasis, and hydatid echinococcosis patients with organic visceral abnormalities. The levels of antibodies against alpha-mp correlated with the severity of pathology [44]. S. mansoni PM peptide smp97 is a homologue of alpha-mp [25]. This fact suggests that there is a relationship between the development of an immune response to Pmes immunological processes in helminthiases. The relationship between organic visceral pathology and a competitive with serum IgE serum IgG4 hyperproduction at the early [6] and late stages of the studied helminthic infections was revealed. One may resume that this balance of production of these isotypes is not beneficial for the development of disease as IgG4-antibody hyperproduction is not beneficial for reinfection resistance [26, 28, 54]. One of the mechanisms may be serum IgG4 blocking the antibody-dependent cytotoxic effect, as it was supposed for unspecific IgE hyperproduction [47]. The selected development of cardiomyopathy or obstructive fibrosis in the lung after trichinellosis [2, 6, 45], endomyocardiofibrosis in the foci of filariases [21, 31] suggests that their development like resistance or susceptibility to infections [54] should be programmed.

Chronic Disease↗

Cytokine-mediated regulation of intestinal helminth infections: the Trichuris muris model.

The Trichuris muris-mouse model of intestinal helminth infection provides a convenient system to examine the immune mechanisms operating during acute and chronic infection. Particular subsets of helper T lymphocytes (CD4+Th cells) play an important role in regulating infection via the secretion of distinct groups of cytokines. Reciprocal activation of Th cell subsets is associated with either expulsion of the parasites from the intestine (Th2 cells) or chronic infection (Th1 cells). In vivo neutralization experiments using anti-cytokine monoclonal antibodies show that critical cytokines are involved, with interferon-gamma playing an important role in the establishment of chronic trichuriasis and interleukin-4 in expulsion of the parasite from the gut. This model has provided clear evidence of a crucial role for distinct cytokines in mediating host protection against intestinal helminth infection and that manipulation of the immune response through the Th cell-cytokine axis can benefit either the host or the parasite. As such, the T. muris model is poised to generate important new data relevant not only to intestinal helminthiasis but to the wider field of parasite immunity and infection in general.

Animals↗

On the solution of mathematical models of herd immunity in human helminth infections.

The general solution of the mathematical model of herd immunity to human helminth infections recently proposed by Anderson and May is obtained. The numerical solution of a more accurate biological model is indistinguishable from the corresponding exact solution of a more tractable mathematical model. Computer simulations of some particular cases of this model support the notion that both ecological and immunological factors determine the observed convex patterns of age-prevalence and age-intensity curves of human helminth infections.

Animals↗

Epidemiological patterns of gastrointestinal and lung helminth infections in grazing calves in The Netherlands.

The patterns of gastrointestinal and lung helminth infections in grazing calves were studied in two small grazing experiments carried out between May and October in 1985 and 1986, respectively, at Utrecht State University. For lungworm a very rapid translation of infective larvae was seen in both experiments, resulting in a rapid build-up of the worm burdens, and in July the second generation of Dictyocaulus caused husk. After the end of patency for lungworm, in the beginning of August, a rapid decrease in pasture infectivity, measured by pasture larval counts and worm counts of tracer calves, was observed. For the gastrointestinal nematodes the translation of infective larvae was much slower as a distinct 'midsummer increase' of pasture infectivity was not seen before the end of July. The worm counts of the tracer calves and the pasture larval counts showed that these larvae remained on pasture much longer than the lungworm larvae. As in Dictyocaulus, patency stopped in August-September in Nematodirus but not in Ostertagia and Cooperia, indicating a slower rate of development of immunity in both latter genera. In contrast to lungworm, the results indicate a clear and predictable seasonal pattern for gastrointestinal helminth infections.

Animals↗

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↗

Saturation of immunoglobulin E (IgE) binding sites by polyclonal IgE does not explain the protective effect of helminth infections against atopy.

One hypothesis for the decreased rates of atopy observed among helminth-infected individuals is that parasite-induced polyclonal immunoglobulin E (IgE) out-competes allergen-specific IgE for FcepsilonRI binding on basophils and mast cells. In experiments with fresh blood drawn from filaria-infected patients, we found no association between ratios of polyclonal to Brugia malayi antigen (BmAg)-specific IgE (range, 14:1 to 388:1) and basophil responses to BmAg as measured by histamine release. Using serum samples from a filaria-infected patient who also had dust mite (Dermatophagoides pteronyssinus)-specific IgE antibodies from time points with various ratios of polyclonal to D. pteronyssinus-specific IgE (16:1 to 86:1), we demonstrated that increased ratios of polyclonal to D. pteronyssinus-specific IgE did not attenuate basophil sensitization as measured by D. pteronyssinus-specific histamine release. Suppression of histamine release was likely not observed in either of these sets of experiments because polyclonal to antigen-specific IgE ratios were not sufficiently high, as concurrent passive sensitization of basophil experiments required ratios of polyclonal to antigen-specific IgE of greater than 500:1 to suppress basophil histamine release. Further, the intensity of IgE staining in basophil populations from 20 patients with active filaria infections correlated strongly with total serum IgE levels (rho = 0.698; P = 0.0024) with no plateau in intensity of IgE staining, even though some patients had total IgE levels of greater than 10,000 ng/ml. Our data therefore suggest that in helminth infections (and in filarial infections in particular), the ratios of polyclonal to allergen-specific IgE rarely reach those levels necessary to inhibit allergen-specific IgE-FcepsilonRI binding and to suppress allergen-induced degranulation of mast cells and basophils.

Animals↗

The role of helminth infections in protection from atopic disorders.

PURPOSE OF REVIEW: The observation that allergies are less prevalent in developing countries, especially in rural areas, has stimulated considerable research to identify environmental factors associated with protection against allergic disorders. Here, we review recent studies conducted in developing countries. RECENT FINDINGS: Epidemiological studies conducted in South America, Asia and Africa have attempted to identify factors associated with differences in prevalence of atopy, asthma and atopic dermatitis. Particular attention is given to the complex relationship between helminth infections and allergies. In answer to the question of whether helminth infections are associated with protection against allergic disorders, conflicting data have been generated. In addition to epidemiological studies, animal models have been utilized to gain insight into the immunological mechanisms involved in the interaction between helminth infections and allergies. These animal studies are discussed. The possible explanations for discrepancies found within both human and murine studies have been considered, highlighting the need for further research. SUMMARY: An in-depth understanding of the relevant protective mechanisms against allergic disorders will open the possibility of developing novel therapeutics to prevent the allergic march worldwide.

Allergens↗

Influence of helminth infections on the clinical course of and immune response to Leishmania braziliensis cutaneous leishmaniasis.

BACKGROUND: Helminth infections influence the clinical outcome of and immune response to certain immune-mediated diseases. METHODS: We conducted a cohort study of 120 patients to examine the role that intestinal helminth infection plays in the clinical course of and immune response to cutaneous leishmaniasis (CL) treated with pentavalent antimony. RESULTS: Patients coinfected with Leishmania braziliensis and helminths took longer to heal (relative hazard for healing, 0.47 [95% confidence interval, 0.26-0.85]; P=.01) than patients with CL without helminths, with 70% of coinfected patients being cured at 90 days, compared with 92% of helminth-free patients. Coinfected patients had an immune response shifted toward the T helper 2 type, with increased total immunoglobulin E levels (P<.06) and a tendency toward increased interleukin-5 levels, compared with helminth-free patients with CL. CONCLUSIONS: Helminths influence both the clinical outcome and the immune response of patients with CL. These results may have clinical implications for the care of patients with CL caused by Leishmania braziliensis, because screening for and treatment of helminths may improve responses to treatment and possibly reduce the risk of progression to mucosal disease.

Adolescent↗

Effect of intestinal helminth infection on some nutritional parameters among rural villagers in Nepal.

We report the prevalence of intestinal helminthiasis and its impact on health of Nepalese in two different rural Village Development Committees (VDC) in Nepal. A total of 261 school children from Okharpauwa VDC in Nuwakot district (Central Region) and 242 inhabitants of Boya VDC in Bhojpur district (Eastern Region) in Nepal were included in this study. The overall prevalence in these two different districts were 57.5% and 55.4%, respectively. Altogether four types of helminths were detected. In both districts, Ascaris lumbricoides was the commonest helminth. Mixed helminth infection in both study areas accounted for less than 5.0%. All helminth infected subjects were treated with a single dose of albendazole. Heavy Trichuris trichiura infection needed a second dose. Blood hemoglobin and serum total protein level in school children in Okharpauwa VDC increased significantly after chemotherapy (P < 0.05). Eosinophil count (10.1%; SD 5.0325) returned to normal (4.8%; SD 4.6997). Helminth infection in Boya VDC was more common in children than in adults. Serum total protein, albumin, total cholesterol and triglycerides levels were not influenced by the presence or absence of helminths among the inhabitants of Boya VDC. In both districts, more than 80.0% of the household had no latrine. In Boya VDC, 94.0% of inhabitants interviewed were not aware of other intestinal parasite other than A. lumbricoides.

Adolescent↗

Immune dysregulation in Ethiopian immigrants in Israel: relevance to helminth infections?

The infectious disease background and particularly the helminth infections that are endemic in Africa could have profound effects on the host immune system. Studies that we have performed on an Ethiopian HIV- immigrant population that has recently reached Israel, lend support to this notion. They have indeed revealed a very high prevalence of helminth and several other infections with an extreme immune dysregulation, consisting of: (i) highly elevated plasma IgE, IgG, placental isoferritin, p75 soluble TNF receptor (sTNFR) levels and very high blood eosinophilia; (ii) increased secretion from phytohaemagglutinin (PHA)-simulated peripheral blood mononuclear cells (PBMC) of the cytokines IL-2, IL-4, IL-10 and p75 sTNFR, and decreased secretion of interferon-gamma (IFN-gamma) and IL-6; (iii) increased and decreased surface expression of p75 TNFR and IL-6 receptor on lymphocytes, respectively. The causal relationship between this immune dysregulation and the infectious background is highly suggestive, and could have far-reaching implications in the resistance to other infections.

Black or African American↗

Soil-transmitted helminth infections in school children from Cocle Province, Republic of Panama.

A survey was carried out to determine values for the prevalence and intensity of infection of intestinal helminths in children living in Cocle Province, Republic of Panama. The data set consisted of the results of microscopic examinations (modified Kato Katz technique) of stool samples collected in November 1987 from 661 children attending primary schools in 4 communities in the province. The overall prevalences of Ascaris lumbricoides, hookworm and Trichuris trichiura infections were found to be 18.2, 12.0 and 27.5% respectively. There were significant differences between the infection prevalence values for children attending the different schools, but not with respect to age or sex. Positive associations were detected between particular pairs of infections and these were most evident when Trichuris trichiura was involved. The data revealed evidence of a positive association between siblings at one school only for each helminth infection. There was extreme variation in the values for intensity of infection (20-126180 epg for A. lumbricoides). Highly significant, and unexplained, differences were observed in the intensity of A. lumbricoides infection by primary school; this finding did not apply to hookworm or T. trichiura. The analysis also revealed that children heavily infected with A. lumbricoides were also likely to be heavily infected with T. trichiura. Comparisons with the results of surveys carried out in Cocle Province in 1926 and 1974 indicate that these infections are declining in this region of Panama.

Analysis of Variance↗

Epidemiology of helminth infections: implications for parasite control programmes, a South African perspective.

OBJECTIVES: To determine the epidemiology of helminthic infections and the efficacy of parasite treatment among rural South African primary school children in the province of KwaZulu-Natal. To assess the South African government's parasite control policy. METHODS: The study recruited 268 school children, aged 8 to 10, and randomly allocated them into treatment and placebo groups (treatment consisted of a single dose of albendazole (400 mg) and praziquantel (40 mg/kg)). Anthropometric measurements and the prevalence and intensity of helminth infections were taken at baseline (prior to treatment) and 16 weeks post treatment. Two weeks after treatment prevalence and intensity were again measured for an approximate 50% sub-sample of the children to investigate efficacy of treatment. An analysis of the South African government's policies concerning parasite control is assessed in the light of these epidemiological findings. RESULTS: Low levels of both stunting and wasting were observed throughout the study (approximately 10% and 1%, respectively), but did not vary significantly across either treatment group or time period (P >0.50). At baseline the observed prevalences for the three main helminths found in this study among the treated children were Ascaris lumbricoides 29.5%, Trichuris trichiura 51.9% and Schistosoma haematobium 22.3%. These prevalences declined significantly to 4.7% (P <0.0005), 38.0% (P < 0.03), and 3.3% (P < 0.0002), respectively, 16 weeks post treatment. The majority of infections observed at baseline were of light intensity, namely A. lumbricoides (50%), T. trichiura (80%) and S. haematobium (100%), and following treatment these levels were reduced significantly (P <0.0001, P< 0.05 and P < 0.005, respectively). The levels of both prevalence and intensity in the untreated group remained constant. The cure rates over the first two weeks of the study were found to be 94.4% for A. lumbricoides, 40% for T. trichiura and 72.2% for S. haematobium. CONCLUSION: The benefits of targeted, school-based treatment in reducing the prevalence and intensity of infection supports the South African government's focus of using school-based interventions as part of an integrated parasite control programme. These strategies and programmes are consistent with recommendations of the World Health Organization (WHO) and The United Nations Children's Fund (UNICEF).

Albendazole↗

The role of Th2 cytokines, chemokines and parasite products in eosinophil recruitment to the gastrointestinal mucosa during helminth infection.

Trichinella spiralis and Trichuris muris are nematode parasites of the mouse, dwelling in the small and large intestines, respectively: worm expulsion requires development of a Th2 immune response. The chemokine CCL11 is agonist for the chemokine receptor CCR3 and acts in synergy with IL-5 to recruit eosinophils to inflammatory sites. The role of CCL11 in gastrointestinal helminth infection has not been previously studied. We challenged wild-type (WT) BALB/c, CCL11 single knockout (SKO) and CCL11 IL-5 double knockout (DKO) mice with either T. spiralis muscle larvae or T. muris eggs in order to examine eosinophil recruitment to the small and large intestine during helminth infection. A peripheral eosinophilia was seen in WT and SKO mice during T. spiralis infection but not with T. muris. Gastrointestinal eosinophilia was markedly reduced but not ablated in SKO mice -- and negligible in DKO mice -- infected with either nematode. The residual eosinophilia and up-regulation of CCL24 mRNA in the gastrointestinal tract of SKO mice infected with either nematode, together with the presence of an eosinophil-active factor in T. spiralis and T. muris products, suggest that CCL11 is the salient but not the sole eosinophil chemoattractant of biological significance during gastrointestinal helminth infection.

Animals↗

Immunodiagnostic tests for protozoan and helminthic infections.

Immunodiagnostic tests for human protozoan and helminthic infections are reviewed. The need for immunodiagnostic tests varies with each infection but is of paramount importance in those infections that cannot be parasitologically diagnosed readily such as toxoplasmosis, pneumocystosis, Chagas' disease, trichinosis, hydatidosis, cysticercosis, and visceral larva migrans. Immunoassays are also needed for those worldwide highly prevalent infections with severe morbidity to be used in seroepidemiology and in the follow-up evaluation of control programs. The most important are malaria, schistosomiasis, onchocerciasis, lymphatic filariasis, and trypanosomiasis. Major advances have been made in the use of enzyme-linked immunosorbent assay (ELISA) as a practical and rapid test for use in endemic countries and in the identification and isolation of diagnostic parasite antigens aided in particular by the use of monoclonal antibodies. Development of immunodiagnostic tests for specific parasite antigens in body fluids for many infections is being actively pursued.

Amebiasis↗

Antigen-specific cellular hyporesponsiveness in a chronic human helminth infection is mediated by T(h)3/T(r)1-type cytokines IL-10 and transforming growth factor-beta but not by a T(h)1 to T(h)2 shift.

Exposure to infective larvae of the filarial nematode Onchocerca volvulus (Ov) either results in patent infection (microfilaridermia) or it leads to a status called putative immunity, characterized by resistance to infection. Similar to other chronic helminth infections, there is a T cell proliferative hyporesponsiveness to Ov antigen (OvAg) by peripheral blood mononuclear cells (PBMC) from individuals with patent infection, i.e. generalized onchocerciasis (GEO), compared to PBMC from putatively immune (PI) individuals. In this study, mechanisms mediating this cellular hyporesponsiveness in GEO were investigated: the low proliferative response in PBMC from GEO individuals was associated with a lack of IL-4 production and significantly lower production of IL-5 compared to those from PI individuals, arguing against a general shift towards a T(h)2 response being the cause of hyporesponsiveness. In contrast, IL-10 and transforming growth factor (TGF)-beta, two cytokines associated with a T(h)3 response, seemed to mediate hyporesponsiveness: PBMC from individuals with GEO produced significantly more IL-10, and T cell proliferative hyporesponsiveness in this group could be reversed by the addition of anti-IL-10 and anti-TGF-beta antibodies. Hyporesponsiveness was specific for OvAg and not observed upon stimulation with related nematode antigens, arguing for a T cell-mediated, Ov-specific down-regulation. Ov-specific T cells could be cloned from GEO PBMC which have a unique cytokine profile (no IL-2 but high IL-10 and/or TGF-beta production), similar to the T cell subsets known to suppress ongoing inflammation (T(h)3 and T(r)1), indicating that this cell type which has not been found so far in infectious diseases may be involved in maintaining Ov-specific hyporesponsiveness.

Animals↗