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Immunological aspects of human schistosomiasis.

Helminth infections are characteristically associated with Th2-dependent responses leading to IgE production and eosinophilia. However, the effect of such responses varies between different hosts. In murine schistosomiasis, for example, Th1 responses are associated with protection against infection, and Th2 responses with egg-induced morbidity. In human schistosomiasis, in contrast, Th2 responses with the production of IgE antibodies against a restricted range of adult worm antigens are associated with protection against reinfection after chemotherapy, while individuals in whom Th2 responses against egg antigens predominate show less severe egg-associated morbidity than those in whom Th1 responses predominate. It is suggested that Th2-mediated responses are selectively advantageous to the human host in the context of schistosomiasis and possibly other helminth infections. The implications of this for vaccination, for control through chemotherapy, and for the study of interactions with other infections are briefly discussed.

Adolescent↗

Allergy, parasites, and the hygiene hypothesis.

The increase of allergic diseases in the industrialized world has often been explained by a decline in infections during childhood. The immunological explanation has been put into the context of the functional T cell subsets known as T helper 1 (TH1) and T helper 2 (TH2) that display polarized cytokine profiles. It has been argued that bacterial and viral infections during early life direct the maturing immune system toward TH1, which counterbalance proallergic responses of TH2 cells. Thus, a reduction in the overall microbial burden will result in weak TH1 imprinting and unrestrained TH2 responses that allow an increase in allergy. This notion is contradicted by observations that the prevalence of TH1-autoimmune diseases is also increasing and that TH2-skewed parasitic worm (helminth) infections are not associated with allergy. More recently, elevations of anti-inflammatory cytokines, such as interleukin-10, that occur during long-term helminth infections have been shown to be inversely correlated with allergy. The induction of a robust anti-inflammatory regulatory network by persistent immune challenge offers a unifying explanation for the observed inverse association of many infections with allergic disorders.

Antibody Specificity↗

Perceptions and treatment of intestinal worms in rural Bangladesh: local differences in knowledge and behaviour.

A survey was conducted on 131 mothers in rural Bangladesh to examine knowledge and perceptions of helminth infection in relation to use of health facilities and treatment-seeking behaviour. Almost all respondents considered worms to be a cause of bad health and a high percentage of mothers had obtained deworming treatment for their children. However, marked differences were found in mothers' descriptions of the causes and prevention of helminth infection in two adjacent areas; Pullakandi and Shekpara. The discrepancies in biomedical knowledge corresponded with differences in treatment-seeking behaviour in the two areas. All households in the area had access to free deworming treatment provided by a health clinic, but this facility was predominantly used by women living nearby in Pullakandi. Because of the cultural and social constraints on female activities, women living further from the clinic, in Shekpara, preferred to send their husbands to a pharmacy in the nearby town to buy deworming treatment. As a consequence, these households were at a relative disadvantage in respect of the low exposure of women to health education and the greater financial cost of deworming treatment. The study highlights the influences of social and cultural factors on treatment-seeking behaviour, which in turn affect women's exposure to health education and biomedical knowledge of helminths. Further questions are raised, however, on the ability of women to implement preventive measures and the impact of health education on rates of parasitic infection.

Adolescent↗

Human IgE, IgG4 and resistance to reinfection with Schistosoma haematobium.

A well recognized feature of the immune response to parasitic helminth infections, including schistosomiasis, is the production of large amounts of specific and nonspecific IgE1,2. Immunological pathways involving IgE can lead to damage to the developing schistosomulum and it has been suggested that responses involving IgE could have evolved as protection against helminth infections. There has been no epidemiological evidence to support this idea and the only significant IgE responses known in man are those involved in the pathogenesis of allergic disease. Here we measure serological response during reinfection with S. haematobium and demonstrate that IgE antibodies in man can be beneficial. Our results support the hypothesis that the slow build-up of IgE to high levels and the early production of IgG4 antibodies, which may block IgE pathways are responsible for delaying the development of protective immunity to S. haematobium.

Adolescent↗

A Brugia malayi antigen specifically recognized by infected individuals.

Western blot analyses were performed on 444 serum specimens: 40 sera from microfilaraemic individuals, 10 sera from elephantiasis patients, 24 treated individuals, 50 sera from residents of endemic areas without anti-filarial IgG4 antibodies (endemic normals), 20 sera from amicrofilaraemic individuals with high anti-filarial IgG4 antibodies, 200 sera from healthy city-dwellers (non-endemic samples), and 100 sera from soil-transmitted helminth-infected individuals. Phast electrophoresis system was used to electrophorese Brugia malayi soluble adult worm antigen on 10-15% SDS-PAGE gradient gels followed by electrophoretic transfer onto PVDF membranes. Membrane strips were then successively incubated with blocking solution, human sera, and monoclonal anti-human IgG4 antibody-HRP, with adequate washings done in between each incubation step. Luminol chemiluminescence detection was then used to develop the blots. An antigenic band with the MW of approximately 37 kDa was found to be consistently present in the Western blots of all microfilaraemic sera, all amicrofilaraemic sera with high titres of anti-filarial IgG4 antibodies, some treated patients, and some elephantiasis patients. The antigen did not occur in immunoblots of individuals with other helminthic infections, normal endemic individuals, and city dwellers. Therefore the B. malayi antigen of with the MW of approximately 37 kDa demonstrated specific reactions with sera of B. malayi-infected individuals and thus may be useful for diagnostic application.

Adult↗

The influence of sampling effort and the performance of the Kato-Katz technique in diagnosing Schistosoma mansoni and hookworm co-infections in rural Côte d'Ivoire.

The Klato-Katz method is widely used for diagnosing helminth infections in epidemiological surveys, but is known to have a low sensitivity. In the case of Schistosoma mansoni, statistical methods have been developed to compensate for the poor sensitivity, but the same is not true of any other helminth parasite, or infections with multiple-helminth species. We screened 101 schoolchildren from a rural area of Côte d'Ivoire over 5 consecutive days and made 5 Kato-Katz readings from each stool specimen. We estimated single and dual-species infections with S. mansoni and hookworm based on raw egg count data and after developing a latent-class model. The cumulative prevalence of co-infections was estimated at 9.9% after reading slides on the first day, and 57.0% after reading all 25 slides per person. The latent class model yielded a co-infection prevalence estimate of 79.6%, with marginal prevalence estimates for hookworm and S. mansoni infections of 83.9% and 91.6% respectively. The sensitivities of a single Kato-Katz thick smear for detection of S. mansoni alone, hookworms alone, or S. mansoni plus hookworms were 22.4%, 8.0% and 17.7%, respectively. In the current setting this could be attributable to low infection intensities of both parasites, combined with intra-specimen and day-to-day variation in egg output. If confirmed in other settings, these findings have implications for estimating the prevalence of multiple species helminth infections, and hence the design and implementation of efficacious and cost-effective control programmes.

Ancylostomatoidea↗

Nippostrongylus brasiliensis: changes in plasma levels of gastrointestinal hormones in the infected rat.

Plasma concentrations of gastrointestinal hormones were measured by radioimmunoassay in fasted rats 9 days after infection with a range of doses of Nippostrongylus brasiliensis. Values for infected rats fed ad libitum were compared with those of weight matched, pair fed, uninfected rats to control for the possible effects of dose-dependent reductions in food intake associated with infection. The plasma concentrations of some of the gastrointestinal hormones in infected rats were very different from those of their pair fed partners. The magnitude and direction of the changes varied according to the hormone being examined. Plasma concentrations of gastrin and pancreatic polypeptide were similar in pair fed and infected rats at all doses used. For the other hormones assayed, infection was associated with dose-related changes. The plasma concentrations of cholecystokinin and insulin were slightly but significantly reduced in infected rats. In contrast, secretin, enteroglucagon, and pancreatic glucagon concentrations were markedly increased. At the highest dose given (52 larvae/g body wt), the plasma levels of secretin and enteroglucagon in infected rats were elevated 9 X and 15 X, respectively. A comparison of the changes seen in N. brasiliensis-infected rats with those reported for other helminth infections revealed striking differences. The possible etiology of alterations in plasma gastrointestinal hormone concentrations and their contribution to the pathological changes seen in animals infected with helminths are discussed.

Animals↗

Helminthic food-borne infections.

The importance of food-borne helminthic infections is not well recognized and has not received the same attention as food-borne bacterial infections. Poverty, overpopulation, and cultural practices contribute to conditions that maintain food-borne helminthic infections. The development of better means of transportation and the ease of reaching otherwise inaccessible markets have increased significantly our risk of coming in contact with food containing infectious organisms. The education of industry, public health workers, governmental organizations, and consumers is the most effective means to prevent food-borne helminthic infections and safeguard the world's food supply. Prevention and intervention measures focused at the production level to disrupt the parasite's life cycle are critical for maintaining a safe food supply.

Animals↗

Effect of deworming on human T cell responses to mycobacterial antigens in helminth-exposed individuals before and after bacille Calmette-Guérin (BCG) vaccination.

The protective efficacy of BCG vaccination against pulmonary tuberculosis (TB) is highly variable in different populations. The reason remains to be elucidated. This study aims to investigate the possible effect of intestinal helminths on the immune response to PPD in naturally immunized or BCG-vaccinated humans. The study population was assessed for helminthic infection and those found to be positive were randomly assigned to either an albendazole treatment group or a control group who received a placebo. The immune response to PPD was compared between the two groups. In addition, subjects who were tuberculin skin test-negative in both groups were BCG vaccinated and later on tested for PPD-specific responses. Albendazole induced elimination/or reduction in intestinal worms resulting in a significant improvement in T cell proliferation and in interferon-gamma production by peripheral blood mononuclear cells (PBMC) stimulated with PPD. Moreover, BCG vaccination significantly improved PPD-specific immune responses in the treated group but not in the placebo group. The differences in the in vivo skin test responses were not significant. The data show that cellular immune responses to PPD are reduced in persons with concurrent helminthic infections, perhaps reflecting a lowered resistance to mycobacterial infections. This could explain, at least in part, the reduced efficacy of BCG against TB in helminth-endemic areas of the world.

Adolescent↗

Serodiagnosis of human onchocerciasis: evaluation of sensitivity and specificity of a purified Litomosoides carinii adult worm antigen.

Sensitivity and specificity of a Litomosoides carinii macrofilariae aqueous crude extract and a purified antigen which was isolated by preparative flat bed electrofocusing, were evaluated for the immunodiagnosis of human onchocerciasis in 3 serological tests: Double diffusion test (DT), latex agglutination test (LAT) and ELISA. Testing sera from proven cases of onchocerciasis (n = 28), loiasis (n = 4) filariasis bancrofti (n = 4), and other non filarial helminth infections (n = 29) in all tests the purified antigen was clearly more sensitive and specific. Testing onchocerciasis sera highest sensitivity was found by ELISA (92.9%) followed by latex agglutination test (89.3%) and double diffusion test (82.1%). Specificity controls of the purified antigen with sera from patients with helminth infections others than filariases led to 0% (DT), 6.9% (LAT) and 10.3% (ELISA) false positive reactions. When the 3 tests were used in combination in a way that at least two positive reactions in different tests were regarded as necessary to declare a serum as positive, sensitivity increased to 100% and unspecific reactions were found only testing one serum (3.4%) originating from a case of cystic echinococcosis.

Antibodies↗

Immunodiagnosis of toxocarosis in humans: evaluation of a new enzyme-linked immunosorbent assay kit.

Excretory/secretory (E/S) antigen derived from second-stage larvae of Toxocara canis maintained in defined medium in vitro has been well established worldwide for the immunodiagnosis of human toxocarosis by enzyme-linked immunosorbent assay. Such an enzyme-linked immunosorbent assay, based on the detection of human anti-T. canis (E/S antigen) serum immunoglobulin G, has recently been commercialized by Biokema-Affinity Products (Crissier-Lausanne, Switzerland). This commercial test kit was evaluated with regard to its application in a routine diagnostic laboratory and the reliability of the results. Of 78 patients with suspected clinical toxocarosis, 71 had anti-T. canis antibodies (positive serological result) corresponding to a diagnostic sensitivity of 91%; 14% of serum samples (n = 199) from patients with protozoan or with helminthic infections also showed positive reactions mainly related to infections with Trichinella, Strongyloides, and Fasciola species. An epidemiological study with 1,000 serum samples from randomly selected healthy blood donors and children in Switzerland demonstrated a seroprevalence of 2.7%. The test kit under evaluation had an overall diagnostic sensitivity of 91% and a relative specificity of 86%, the latter being related to some protozoan and helminthic infections. Because of the scarcity of such infections, potential cross-reactivity does not play a major role under the conditions found in the middle part of Europe. In conclusion, the application of the test kit provided for use in this study can be recommended for routine diagnostic use.

Animals↗

IL-18, although antiallergic when administered with IL-12, stimulates IL-4 and histamine release by basophils.

IL-18 is a proinflammatory cytokine that plays an important role in natural killer cell activation and T helper 1 (Th1) cell responses. Mast cells and basophils are major inducers and effectors of allergic inflammation. Here we show that basophils and mast cells derived by culture of bone marrow cells with IL-3 for 10 days express IL-18Ralpha chain and that basophils produce large amounts of IL-4 and IL-13 in response to stimulation with IL-3 and IL-18. Injection of IL-12 and IL-18 inhibits IgE production in helminth-infected wild-type mice and abolishes the capacity of their basophils to produce IL-4 and IL-13 in response to stimulation either with IL-3 and IL-18 or with FcepsilonR cross-linkage. By contrast, this combination of cytokines actually increases IgE levels in helminth-infected IFN-gamma(-/-) mice and enhances IL-4 and IL-13 production by their basophils. Furthermore, injection of IL-18 alone enhances basophil production of IL-4 and histamine both in wild-type and IFN-gamma(-/-) mice. Thus, IL-18 has the potential to stimulate basophils but, when given with IL-12, exhibits an antiallergic action in vivo.

Animals↗

[Trichinellosis outbreaks in Spain (1990-2001)].

INTRODUCTION: Trichinellosis is a helminth infection having a wide geographical distribution. It is acquired by ingestion of raw or undercooked meat infected with Trichinella spp. The present work reviews the human trichinellosis outbreaks recorded in Spain during 1990-2001, taking into account both the geographical distribution and source of the infection. METHODS: The parasite was isolated from suspected meats with the digestion technique. Molecular characterization of Trichinella isolates was done by random amplified polymorphic DNA (RAPD) analysis and Western-blot with US5 and US9 monoclonal antibodies. Anti-Trichinella antibodies in the patients' sera were investigated by indirect immunofluorescence (IIF). RESULTS: A total of 49 trichinellosis outbreaks were detected in Spain during 1990-2001, 75.5% produced by ingestion of infected wild boar, 14.3% by infected domestic pig and 10.2% by an unknown source. Of the 49 outbreaks, 21 were followed up in our laboratory. We were able to perform molecular identification of the Trichinella species involved in 13 outbreaks, with 61.5% produced by T. britovi and 38.5% by T. spiralis. Serological diagnosis of the trichinellosis patients by IIF allowed confirmation of helminth infection. CONCLUSIONS: With the use of molecular markers, T. spiralis and T. britovi were identified as the causative organisms in trichinellosis outbreaks detected in Spain during 1990-2001. These results reveal the importance of T. britovi in Spanish public health.

Animals↗

Tuft cell acetylcholine is released into the gut lumen to promote anti-helminth immunity.

Upon parasitic helminth infection, activated intestinal tuft cells secrete interleukin-25 (IL-25), which initiates a type 2 immune response during which lamina propria type 2 innate lymphoid cells (ILC2s) produce IL-13. This causes epithelial remodeling, including tuft cell hyperplasia, the function of which is unknown. We identified a cholinergic effector function of tuft cells, which are the only epithelial cells that expressed choline acetyltransferase (ChAT). During parasite infection, mice with epithelial-specific deletion of ChAT had increased worm burden, fitness, and fecal egg counts, even though type 2 immune responses were comparable. Mechanistically, IL-13-amplified tuft cells release acetylcholine (ACh) into the gut lumen. Finally, we demonstrated a direct effect of ACh on worms, which reduced their fecundity via helminth-expressed muscarinic ACh receptors. Thus, tuft cells are sentinels in naive mice, and their amplification upon helminth infection provides an additional type 2 immune response effector function.

Animals↗

Toxocariasis: serological diagnosis by enzyme immunoassay.

An enzyme-immunoassay was developed to measure the concentration of serum antibody specific for the secretory antigens released by migrating toxocaral larvae. This technique was evaluated by testing sera from healthy UK adults, and from patients with and without toxocariasis. In 922 healthy adults, 2.6% were found to have elevated specific antibody levels. Elevated values were observed twice as frequently in males as in females but showed no significant regression with age between 20 and 65 years. Of 62 patients with non-toxocaral helminthic infections, all had antitoxocaral antibody levels within the range of values observed in healthy controls and had a mean level which was not significantly elevated. All of 13 patients with clinical toxocariasis had enzyme-linked immunosorbent assay (ELISA) antibody levels above the 100th percentiles of both the healthy population and the helminth-infected group and had a significantly high mean value (p less than 0.001) more than 12 times that of the healthy or infected controls. The high degree of sensitivity and specificity of the toxocariasis enzyme-immunoassay indicates that this new test should be useful in reference immunodiagnostic applications and in large-scale seroepidemiological surveys.

Antibodies↗

Intestinal helminthiasis, nutritional status, and their relationship; a cross-sectional study in urban slum school children in Indonesia.

In a study of urban slum school children (276 boys and 231 girls), in Ujung Pandang, Indonesia, parasitological and anthropometric exams were cross-sectionally performed to assess prevalence and intensity of helminth infections and nutritional status. Prevalence of Ascaris, Trichuris and hookworm was 92%, 98%, and 1.4%, respectively. 91% children had both Ascaris and Trichuris infections. About half of the Ascaris- and Trichuris-infected children (46% and 58%, respectively) had moderate infections. Stunting was seen in 55% of the children, while wasting was observed in 10%. Boys had lower nutritional status than girls (p < 0.001), based on weight-for-age (WA) and height-for-age (HA) Z-scores. Age had an inverse relationship with WA and HA Z-scores (p < 0.0004). A relationship between helminth infections and nutritional status was observed between log Trichuris egg count and WA and HA Z-scores after controlling for age, sex, and log Ascaris egg count (p = 0.048 for HA Z-score, and p = 0.058 for WA Z-score). The relationship was also found when Trichuris infection was categorized into mild, moderate, and severe infections (p = 0.017 and p = 0.001 for HA and WA Z-scores, respectively). Scheffe's test for multiple mean comparisons showed that Trichuris-infected children with above 1,000 eggs per gram feces had significantly lower nutritional status than lower epg or non-infected children (p < 0.001 and p < 0.05 for HA and WA Z-scores respectively).

Child↗

Pyogenic liver abscess in children: some observations in the Espírito Santo State, Brazil.

Pyogenic liver abscess in children is uncommon in developed countries and there are few reports about the disease in developing countries including Brazil. As pyogenic liver abscesses in children are frequently diagnosed in Vitória (E. Santo State, Brazil), the records of admissions at the Children's Hospital (Hospital Infantil N.S. da Glória) were surveyed. Sixty-five cases of pyogenic liver abscess were observed over a period of three years, from May 1991 through April 1994 (mean of admissions of 2800 children/year). Fourty-seven cases occurred in boys (mean of ages 8.1 +/- 3.5 yr, median 8 yr) and 18 in girls (mean of ages 6.1 +/- 3.3 yr, median 7 yr) with a 2.7:1 male/female ratio. Predisposing factors were skin infections (23 cases), bile duct ascariasis (six cases), trauma (two cases) but in 30 cases a predisposing factor was not evident. Staphylococcus aureus was the bacteria most frequently isolated (16/29 examined). Entamoeba histolytica trophozoites were never found in the exudate of abscesses and cysts were found once in fecal examination. Clinical manifestations were similar to those observed in other reports about pyogenic liver abscess in children. There was a high frequency of intestinal helminth infection (80.6% of 36 cases in which a fecal examination was recorded) and eosinophilia in the peripheral blood (36.2% of 61 cases). In addition most cases came from the urban periphery of Vitória, where intestinal parasites are frequent. These data showed that the frequency of pyogenic liver abscess is higher in Vitória (one case/138 admissions) than in developed countries (25 cases or less/10,000 admissions in USA). We hypothesyse that the helminth infection (mainly with ascaris and toxocara), whose larvae migrate through the liver inducing granulomas, could enhance the localization of bacteria, increasing the risk for pyogenic liver abscess.

Brazil↗

Failure of twice-weekly iron supplementation to increase blood haemoglobin and serum ferritin concentrations: results of a randomized controlled trial.

In order to increase the intestinal absorption of iron whilst simultaneously minimising the side-effects and thus increasing compliance, once- or twice-weekly, instead of daily, iron supplementation has been widely recommended. In a randomized, placebo-controlled, double-blind study in western Kenya, a tablet of ferrous dextran (containing 60 mg elemental iron) or an identical-looking placebo tablet was provided twice-weekly for 12 months to each child or adult investigated. At baseline each subject had a moderately low blood concentration of haemoglobin (Hb). Initial Hb and serum ferritin (SF) concentrations were determined and each subject was tested for malarial and helminth infection and treated, if necessary, with the appropriate anthelminthic drug(s). Overall, 200 children (aged 4-15 years) and 129 adults (aged 16-63 years) completed the 12-month study. At baseline, 47.5% of the children and 58.1% of the adults were anaemic, hookworm (detected in 60.0% of the children and 69.9% of the adults) was the most common helminth infection, and malaria was endemic. The results of bivariate analyses indicated that twice-weekly iron supplementation had no significant effect on blood Hb or SF concentrations, either in the children or the adults investigated. The results were confirmed in multiple linear-regression analyses, which revealed that the predictors of the final Hb concentration in the children investigated were age and infection, after enrollment, with Ascaris lumbricoides. Gender and the serum concentration of alpha-1-antichymotrypsin (ACT) at final follow-up were predictors of the final SF concentration in the children. In adults, the predictors of the final Hb concentration were gender and HIV infection, and the predictors of the final SF concentration were age and the serum concentration of ACT at the final follow-up. Twice-weekly iron supplementation did not increase Hb or iron stores in children or adults. Since compliance appeared to be high, this lack of effect may be the result of an inadequate dose of iron or of subjects who have deficiencies in micronutrients other than iron.

Adolescent↗