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PubMed1986

IgE antibody and resistance to infection. II. Effect of IgE suppression on the early and late skin reaction and resistance of rats to Schistosoma mansoni infection.

Most helminth parasites induce a strong IgE antibody and elevated eosinophil response in their mammalian hosts and a number of in vitro studies have suggested that IgE, possibly in association with eosinophils, may be an essential element of the host protective immunity against helminth infections. To assess the role of IgE in protective immunity, we examined the effect of suppressing the IgE antibody response on rat immunity to Schistosoma mansoni. Suppression was achieved in neonates by injections of rabbit anti-epsilon chain gamma-globulins, control rats received injections of unspecific gamma-globulins. IgE suppression caused a marked reduction of the inflammatory reaction that developed in the skin of immune rats at the site of a cercarial challenge: the early (30 to 60 min) wheal and flare reaction was abolished, and the late cutaneous reaction (6 to 18 h) associated with intense pruritus, edema and local eosinophilia was greatly reduced. This shows that IgE was critical to the recruitment of effector cells and molecules in the skin during the first 24 h following parasite invasion. Worms were recovered 18 to 30 days after a primary infection and 18 days after a challenge infection from IgE-suppressed and control rats. IgE-suppressed rats cured a first infection as rapidly as the control rats; however, they were two to three times less efficient than the controls at eliminating a second or a third challenge. These observations demonstrate that IgE antibodies are essential for the full development of rat acquired protective immunity against Schistosoma mansoni.

Animals↗
PubMed2004

The Trichuris muris system: a paradigm of resistance and susceptibility to intestinal nematode infection.

Gastrointestinal helminths infect over 1 billion people worldwide. Although rarely causing death, such diseases are associated with high levels of morbidity and furthermore bear a large economic burden within areas where infections are endemic. Trichuris muris, a natural intestinal parasite of mice has been extensively utilised as a laboratory model for the study of human whipworm Trichuris trichiura. This has proven to be an invaluable tool in dissecting the different components involved in immunity to trichuris infection. Moreover, it has become a paradigm of cytokine mediated immunity to gastrointestinal nematodes in general. It is well established that resistance and susceptibility to T. muris infection are tightly associated with the generation of a T helper 2 (TH2) or a T helper 1 (TH1) immune response, respectively. This review gives a detailed account of the experimental work which has provided us with this knowledge, and further builds upon this, by focusing upon the most recent developments and important findings from this host-parasite relationship.

Animals↗
PubMed2006

The beneficial helminth parasite?

There is unequivocal evidence that parasites influence the immune activity of their hosts, and many of the classical examples of this are drawn from assessment of helminth infections of their mammalian hosts. Thus, helminth infections can impact on the induction or course of other diseases that the host might be subjected to. Epidemiological studies demonstrate that world regions with high rates of helminth infections consistently have reduced incidences of autoimmune and other allergic/inflammatory-type conditions. Here I review and assess the possible ways by which helminth infections can block or modulate concomitant disease processes. There is much to be learned from careful analysis of immuno-regulation in helminth-infected rodents and from an understanding of the immune status of acutely and chronically infected humans. The ultimate reward from this type of investigation will likely be a more comprehensive knowledge of immunity, novel ways to intervene in the immune response to alleviate autoimmune and allergic diseases (growing concerns in economically developed areas), and perhaps the development of helminth therapy for patients suffering from specific inflammatory, autoimmune or allergic disorders.

Animals↗
PubMed1990

[Mechanisms of T-cell-mediated hypersensitivity in mice infected with the intestinal helminth Trichinella spiralis].

Intestinal hypersensitivity reactions during parasitic helminth infections are T-cell-dependent. Little is known about the characteristics of T-cells that initiate and regulate intestinal inflammation or about how they do this. In this paper data are presented that indicate that during Trichinella spiralis infections in mice T-cells regulate intestinal inflammation in the same way that they regulate delayed-type hypersensitivity reactions in the skin and cellular immune responses against tumors.

Animals↗
PubMed1990

Effect of drug treatment on the prevalence of intestinal parasites amongst school children in a sub-urban community.

The prevalence of intestinal protozoal and helminthic infection was studied over a period of one year amongst 297 school children, aged 5-20 yr in a sub-urban area. The overall prevalence rate of various protozoal infection, 15.82 per cent had only helminthic infection and 14.47 per cent had combined helminthic and protozoal infection. Ascaris lumbricoides infestation was found to be the commonest helminthic infection (61.70%) while giardiasis was the commonest protozoal infection (59.80%). The prevalence rates, one year after effective anti-protozoal and antihelminthic treatment was administered, were overall parasitic infection 25.92 per cent; only protozoal infection 17.50 per cent, only helminthic infection 5.72 per cent and combined infection 2.69 per cent. The reinfection rate was found to be 7.40 per cent and the fresh infection rate was found to be 11.4 and 39.8 per cent at the end of six months and one year respectively.

Adolescent↗
PubMed2004

Association of intestinal helminths with decreased liver size and sCD23 concentration during falciparum malaria.

To determine if intestinal helminths and the CD23/nitric oxide pathway had an influence on liver size, we conducted a cross-sectional study on 438 patients with confirmed P. falciparum malaria admitted at the Hospital for Tropical Diseases in Bangkok. For all patients the liver size was measured as number of centimeters below the rib cage, a stool examination was conducted, and CD23 and reactive nitrogen intermediates were measured. The median liver size was smaller in helminth-infected patients than in helminth-free patients (chi2 for trend = 9.1, p = 0.003). Liver size significantly increased with the concentration of sCD23 (p < 0.0001). The median sCD23 concentration (OD) was significantly lower in helminth-infected patients than in helminth-free patients, respectively 0.33 (quartiles 0.24-0.57) and 0.45 (quartiles 0.27-0.59), (p = 0.01). There was a negative correlation between sCD23 concentrations and RNI (Spearman's rho = -0.40, p < 0.0001). All the above results remained significant after controlling for potential confounders. These results are compatible with a CD23/NO-mediated decrease in liver size in helminth-infected patients.

Adolescent↗
PubMed2002

Systemic vasculitis with lymphocytic temporal arteritis and Toxocara canis infection.

Vasculitis associated with helminthic infection is rare. We report a case of systemic negative antineutrophil cytoplasmic antibodies vasculitis associated with Toxocara canis infection documented by enzyme-linked immunosorbent assay and Western blot analysis. This case report is unusual because of lymphocytic temporal arteritis and renal involvement. The spontaneous remission of systemic vasculitis without use of steroids or immunosuppressive agents favors a close relationship between vasculitis and the parasite that is more than a coincidental association. To our knowledge, this is the first observation of temporal vasculitis associated with helminthic infection, extending the clinical spectrum of visceral larva migrans.

Aged↗
PubMed1999

Human onchocerciasis and tetanus vaccination: impact on the postvaccination antitetanus antibody response.

To investigate whether helminth infections may affect the efficacy of vaccines by impairing the immune response to nonparasite vaccine antigens, we compared the antibody responses to tetanus toxoid (TT) after tetanus vaccination in 193 subjects with Onchocerca volvulus infection with 85 comparable noninfected controls. After vaccination, the proportions of subjects in each group attaining protective levels of antitetanus antibodies were similar (96.9% infected versus 97.6% noninfected). Postvaccination increases in antitetanus immunoglobulin G (IgG) and the predominant IgG isotype, IgG1, were equivalent in both groups, as were increases in specific IgG4 and IgE; however, significantly greater increases in specific IgG2 (P < 0.05) and IgG3 (P < 0.001) were observed in the noninfected group. Stratification of the O. volvulus-infected group into two groups representing light and heavy infections revealed a significantly impaired antitetanus IgG response in those with heavy infections compared to those with light infections (P < 0.01) or no infection (P < 0.05). The impact of concurrent intestinal helminth infections on the antitetanus response was also examined; an increased IgG4/IgE ratio was seen in those infected with Strongyloides stercoralis (P < 0.05) and when all helminth infections were combined as a single group (P < 0.05). These findings indicate that concurrent infection with O. volvulus does not prevent the development of a protective antitetanus response, although heavier O. volvulus infections are able to alter the magnitude of this response, and concurrent helminth infections (O. volvulus and intestinal helminths) may alter TT-specific antibody isotype responses.

Adolescent↗
PubMed2004

Can helminth antigens be exploited therapeutically to downregulate pathological Th1 responses?

In developing countries where helminth infections are highly prevalent, Th1 autoimmune diseases are almost never reported. A hypothesis suggesting that this may be due to effects of helminth infection on the immune system has been developed, and has inspired scientists to explore the possibility of using helminth antigens to treat autoimmune diseases. In animal models, helminth infection and helminth products have been successfully used to prevent different Th1-mediated autoimmune diseases. Results from initial studies were interpreted based upon the Th1/Th2 paradigm: A Th2-polarizing helminth infection correcting a Th1 autoimmune 'imbalance'. Intriguingly, however, allergies rarely develop in the host, despite the strong Th2 polarization induced by parasite antigens. Helminth infections act on the immune system of the host at many different levels. For this reason, identifying one or more products with therapeutic potential, from the 20,000 genes that a helminth can express, is a challenging task. In this review, we summarize the results achieved in animal models, and suggest possible approaches for the design of therapies appropriate for use in human Th1-mediated autoimmune pathologies.

Animals↗
PubMed2003

[Eosynophils in parasitic infections--clinical and functional significance].

Eosinophils are multifunctional cells which contain and produce many biologically active substances. Their presence is mainly associated with parasitic infections or allergic manifestations. Eosinophilia is a common feature of helminth infections occurring both in the blood and at local sites of infection. The highly toxic basic proteins in eosinophil granules exert a range of biological effects not only against helminth parasites but also in host tissue being responsible for their damage. Eosinophils have been shown to be strong effectors killing helminth parasites in vitro, especially the larval stages. However, this function in vivo was established only for the very small number of parasites. In the last years an opportunity has appeared to perform experiments with parasites on genetically modified mice: over expressing the gene encoding Il-5 as well as lacking some receptors on eosinophils. These new studies in mice demonstrated that Il-5 and eosinophils had a different impact on different helminth infections. Eosinophilia in human patients has only a limited predictive value for the presence of helminth infections. However, the likelihood of the presence of helminth infections increases considerably with the extent of eosinophilia.

Animals↗
PubMed2002

Treatment of intestinal worms is associated with decreased HIV plasma viral load.

BACKGROUND: We have previously suggested that helminthic infections make the host more susceptible to HIV infection and enhance its progression due to the chronic immune activation they cause. OBJECTIVE: To study the effect of antihelminthic treatment on HIV plasma viral load (VL) in HIV- and helminth-infected individuals living in Ethiopia. METHODS: Fifty-six clinically asymptomatic HIV-1-infected individuals, 31 (55%) of whom were also infected with helminths, were studied. All participants received antihelminthic treatment at baseline and at 3 and 6 months. Worm egg excretion, HIV plasma VL, and T-cell subsets were determined at baseline and 6 months after treatment. RESULTS: The mean age, number of CD4 T cells, and gender distribution were similar in the helminth-infected and -noninfected groups. At baseline, HIV plasma VL was strongly correlated to the number of eggs excreted (p <.001) and was higher in individuals infected with more than one helminth (5.28 +/- 0.35 versus 4.30 +/- 1.13 log RNA copies/mL, respectively; p =.16). After treatment of helminths, the 6-month change in HIV plasma VL was significantly different between the successfully treated group and the persistently helminth-positive group (p =.04) CONCLUSIONS: Helminth "load" is correlated to HIV plasma VL, and successful deworming is associated with a significant decrease in HIV plasma VL. The results of the current study, if confirmed in a larger study, may have important implications for slowing disease progression and reducing risks of transmission.

Acquired Immunodeficiency Syndrome↗
PubMed2004

[Infections with helminths and/or protozoa in cats in animal shelters in the Netherlands].

To determine the prevalence of infections with helminths and protozoa in cats in animal shelters, faecal samples from 305 cats from 22 animal shelters in the Netherlands were examined, using a centrifugation-sedimentation-flotation-technique. The association between potential risk factors and the occurrence of an infection was also tested. Infections with helminths and/or protozoa were found in 160 samples (52.5%). Toxocara cati was found in 86 cats (28.2%), Cystoisospora felis in 59 cats (19.3%), Cystoïsospora rivolta in 43 cats (14.1%), Capillaria spp. in 34 cats (11.2%), Ancylostoma tubaeforma in 9 cats (3.0%), Taenia taeniaeformis in 9 cats (3.0%), Aelurostrongylus abstrusus in 8 cats (2.6%), Giardia intestinalis in 3 cats (1.0%), Dipylidium caninum in 2 cats (0.7%) and Toxoplasma gondii in 1 cat (0.3%). The highest prevalence was seen in kittens and stray cats. The main preventive factor against infection was a short stay in a shelter.

Age Factors↗
PubMed2005

Expression of cytokines and monosaccharide transporters in the duodenal mucosa of patients with gastrointestinal symptoms in rural Thailand.

Levels of cytokines and GLUT family monosaccharide transporters in the duodenal mucosa were examined in patients from Nong Khai, Thailand, who had underwent gastroscopy because of gastrointestinal problems. Duodenal biopsy specimens were collected from a total of 33 patients (24 males and 9 females, 45.0 +/- 13.5 years old). Ten patients had present or recent intestinal helminth infections, including strongyloidiasis, taeniasis or ascariasis (group A), 7 were urease-test positive, indicating Helicobacter pylori infection (group B), and 16 had neither helminth infections nor urea-test positivity (group C). Total RNA was extracted from the biopsied specimens and a semi-quantitative RT-PCR was performed. The positivities for IL-13, IL-5 and IFN-gamma mRNA expressions in the patients were 24.2, 60.6 and 100%, respectively, with the highest IL-13 and IL-5 positivities in group A, followed by group C and B. The IL-5 positive rate was significantly higher among patients with high peripheral blood eosinophil counts (> 4%) than in patients with low peripheral blood eosinophil counts. GLUT-1 and GLUT-5 were detectable in all the patients. Although GLUT-1 expressions did not differ among groups A, B and C. GLUT-5 expressions were significantly lower in group B than in group C. These results indicate that helminth and H. pylori infections result in different immunopathological responses in the duodenal mucosa, lower expressions of type 2 cytokines and monosaccharide transporters in H. pylori infections than in helminth infections.

Adult↗
PubMed2001

Helminths, human immunodeficiency virus and tuberculosis.

Helminth infections affect over a quarter of the world's population, especially in the developing countries. These long-lasting parasitic infections cause widespread immune activation and dysregulation, a dominant Th2 cytokine immune profile and an immune hyporesponsiveness state. Considering these profound immune changes and the similar geographic distributions of helminthic infections, HIV and tuberculosis (TB), we suggest that helminthic infections play a major role in the pathogenesis of AIDS and TB. They apparently make the host more susceptible to infection by HIV and Mycobacterium tuberculosis, and impair his/her ability to generate protective immunity against both infections. The implication of these ideas is that without eradication of helminth infections and/or modulation of the immune changes that they cause, HIV and TB vaccines may fail to confer protection against their respective infections in helminth-endemic areas.

AIDS-Related Opportunistic Infections↗
PubMed2006

Respiratory atopic disease, Ascaris-immunoglobulin E and tuberculin testing in urban South African children.

BACKGROUND: Epidemiological relation of intestinal helminth infection and atopic disease, both associated with a T-helper (Th) 2 immune response, is controversial, as it has been reported that helminth infection may either suppress or pre-dispose to atopic disease. This relation has not been tested in an area with a high burden of Mycobacterium tuberculosis (MTB) infection, a known Th1-stimulating infection. OBJECTIVE: To study the association of intestinal helminth infection and atopic disease in a community where helminth infection is endemic and MTB infection is high. METHODS: Three-hundred and fifty-nine randomly selected children aged 6-14 years from a poor urban suburb were tested with allergy questionnaire, skin prick test (SPT) to common aeroallergens, Ascaris-specific IgE (Ascaris-sIgE), fecal examination for pathogenic intestinal helminths and tuberculin skin testing (TST). Histamine bronchoprovocation was tested in the group of children aged 10 years and older. RESULTS: were corrected for demographic variables, socioeconomic status, parental allergy, environmental tobacco smoke (ETS) exposure in the household, recent anthelminthic treatment and for clustering in the sampling unit. Results Ascaris-sIgE was elevated in 48% of children, Ascaris eggs were found in 15% and TST was positive in 53%. Children with elevated Ascaris-sIgE had significantly increased risk of positive SPT to aeroallergens, particularly house dust mite, atopic asthma (ever and recent), atopic rhinitis (ever and recent) and increased atopy-related bronchial hyper-responsiveness. In children with negative TST (<10 mm), elevated Ascaris-sIgE was associated with significantly increased risk of atopic symptoms (adjusted odds ratio (OR(adj)) 6.5; 95% confidence interval (CI) 1.9-22.4), whereas in those with positive TST (>/=10 mm) this association disappeared (OR(adj) 0.96; 95% CI 0.4-2.8). CONCLUSIONS: These results suggest that immune response to Ascaris (Ascaris-sIgE) may be a risk factor of atopic disease in populations exposed to mild Ascaris infection and that MTB infection may be protective against this risk, probably by stimulation of anti-inflammatory networks.

Adolescent↗
PubMed1984

Cell-mediated damage to helminths.

Although it is difficult to draw any sweeping conclusions that would be applicable to all helminth infections, the main features that are emphasized in this review may be summarized briefly. Pathogenic helminths, although extremely diverse in structure and behaviour, have one common feature, namely that they present to the host's defenses large, non-phagocytosable surfaces. Because of this, they are susceptible to a range of effector mechanisms differing either quantitatively or qualitatively from those that are active against other parasites or against normal or abnormal host cells. As an extreme example, the various types of cytotoxic lymphocyte, with one interesting exception, are inactive against helminths. Instead, helminth infections are characterized by high IgE responses and increased numbers of circulating eosinophils. Such eosinophils are activated, and show a marked capacity to kill a variety of target helminths in vitro. Further activation may occur in response to mast cell mediators released as a result of IgE-dependent degranulation; and IgE, as well as IgG and complement, can mediate eosinophil attachment and killing. It may therefore be suggested that the eosinophil/IgE/mast cell axis represents a powerful host defense against helminth infections. IgE can also mediate macrophage-dependent killing of several helminths, a process which involves a functional change in the macrophage, resembling activation. Although eosinophil-mediated and IgE-dependent macrophage-mediated effects are particularly potent, other effector cells are not excluded: in certain circumstances, neutrophils and conventionally activated macrophages may be equally or more effective. Neutrophils appear to act solely by oxidative killing mechanisms, whereas degranulation and the release of toxic granule contents is equally or more important in eosinophil-mediated damage. Different stages of different helminths vary in their degree of susceptibility to different mechanisms. Eosinophils appear to be somewhat less active than neutrophils against ensheathed nematodes, whereas trematodes and exsheathed nematodes are highly susceptible to eosinophil attack. In many experimental helminth infections, studies in vivo suggest a role for antibody-dependent cell-mediated immune effector mechanisms. The identity of the effector cell is difficult to establish because of a lack of techniques for specific manipulation of individual cell types, but histological studies frequently point to a strong eosinophil or macrophage involvement. The development and analysis of in vitro assays allows the study of immune effector mechanisms in man.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed2006

Intestinal parasitic infections among school children of the Dhahira Region of Oman.

OBJECTIVE: To determine the prevalence of intestinal parasitic infections among primary school children in Dhahira region of Oman. METHODS: The study took place in the Dhahira region of Oman from September 2004 to March 2005. We randomly recruited 436 students of 9-10 years of age. Their anthropometric measurements were noted. We collected the stool sample of each student and examined for different intestinal parasites. Stereoscopic microscopy and the World Health Organization's approved KATO-KATZ technique were used. RESULTS: Of the 436 students examined, 65 children (15%) were undernourished (body mass index (BMI) <14 kg/m(2)). The prevalence of intestinal parasitic infections was 38.7% (95% CI 33.2-42.2). The prevalence of protozoan infection was 36% while helminth infection was 9.4%. The prevalence of Entamoeba histolytica/Entamoeba dispar was 24%, Giardia species 10.5% and Escherichia coli 1.4%. The hookworm (Ancylostoma duodenale, Necator americanus), Ascariasis lumbricoides, Trichuris trichiura, Hymenolepiasis nana, Taenia species, Enterobius vermicularis and Strongyloides infections in our study had very low prevalence. Only 29 (6.4%) students had parasitic infection by more than one parasite. The wet zone was significantly associated to the intestinal parasitic infections [Adjusted odds ratio (OR)=3.2 (95% CI 1.9-5.2)]. CONCLUSION: Dhahira region could be classified as low prevalence and low intensity area for soil transmitted helminths infections. However, the magnitude of the protozoan infection was high. The school health program should focus on parasitic infection treatment and addressing the underlying causes of this problem.

Animals↗
PubMed2004

Schistosoma mansoni infection modulates the immune response against allergic and auto-immune diseases.

Chronic Schistosoma mansoni infection leads to a type 2-immune response with increased production of interleukin (IL-10). Evidence indicates chronic exposure to S. mansoni down regulates the type 1 immune response and prevents the onset of Th1-mediated diseases such as multiple sclerosis, diabetes mellitus and Crohn's disease. Furthermore, our own studies have revealed that chronic exposure to S. mansoni also down regulates atopic disease, Th2-mediated diseases. Our studies show an inverse association between the skin prick test reactivity and infection with S. mansoni and show the severity of asthma is reduced in subjects living in an endemic area of S. mansoni. Moreover, we hypothesize the mechanisms involved in the modulation of inflammatory response in atopic individuals, is likely dependent on IL-10 production, an anti-inflammatory cytokine elevated during helminth infections. Patients with asthma and helminth infections produced less IL-5 than patients with asthma without helminth infections, and this down regulation could, in part, be mediated by IL-10. In conclusion, helminthic infections, through induction of regulatory mechanisms, such as IL-10 production, are able to modulate the inflammatory immune response involved in the pathology of auto-immune and allergic disease.

Animals↗