Follow-up study of prevalence and control of ascariasis in swine populations in Serbia

The cause of the most significant helminth diseases in swine — Ascaris suum, can also causes infections in humans. The use of swine manure in agriculture renders the eggs of this ascaridida an accessible source of infection, thus posing a significant risk factor for human health. With the objective of proving the prevalence of infection with A. suum nematodes in the territory of Serbia, investigations were carried out in the period between 2007–2011 in the territories of five districts: North Ba?ka, South Banat, Brani?evo, Zlatibor and Ni?ava. The investigations covered coprological examinations of 1031 feces samples of swine originating from farms owned by individual breeders. The samples were examined using the standard flotation method with a saturated water solution of NaCl. The established prevalence of ascariasis infection amounted to 47.62% (1031/491). The biggest prevalence of infection was determined in the territory of the Brani?evo District, 65.78% (301/198), and the smallest in the territory of the Ni?ava District, 32.24% (183/59). In spite of its prevalence and vast economic importance, there is still insufficient information about the key aspects of the biology and epidemiology of A. suum. Viewed from the aspect of epizootiology, it is very important to know the prevalence of swine infections with Ascaris because of the possible infection of humans by its migrating larvae.     

<Emphasis Type="Italic">Toxocara</Emphasis> and <Emphasis Type="Italic">Ascaris</Emphasis> seropositivity among patients suspected of visceral and ocular larva migrans in the Netherlands: trends from 1998 to 2009

Toxocara canis, Toxocara cati and Ascaris suum are roundworms of dogs, cats and pigs, respectively, that can also infect humans. These zoonotic helminths have a worldwide distribution and are also endemic in the Netherlands. Infection with Toxocara sp. may result in visceral larva migrans (VLM) or ocular larva migrans (OLM) caused by the migrating larvae. Although A. suum has been reported to occasionally mature to the adult stage in humans, clinical cases of VLM suspected to be caused by A. suum have been described. Diagnosis of these helminth infections relies mainly on serology. Here we analyse the results from the Toxocara and Ascaris IgG-ELISA from a total of 2,838 serum samples from VLM and OLM suspected patients that were sent to our institution from 1998 to 2009. Results indicate that for each year the Ascaris seropositivity is significantly higher compared to the Toxocara seropositivity. Furthermore, while Toxocara seropositivity has decreased over time, the Ascaris seropositivity has not significantly changed for the past 12 years. The Ascaris and Toxocara seropositivity was also shown to increases with age and, while gender has no influence on the Ascaris seropositivity, males showed higher Toxocara seropositivity.     

High titre of anti-Ascaris immunoglobulin E associated with bronchial asthma symptoms in 5-year-old rural Bangladeshi children

Background Increasing interest has arisen whether helminthic infections protect against asthma and allergy. The prevalence of wheezing among Bangladeshi children is higher in rural areas where helminthic infectious burden is greater, which is contrary to the general assumption. Objective We therefore examined the association between Ascaris infection, serum level of anti‐Ascaris IgE, which should be investigated differently from the infection, and wheezing in 5‐year‐old children from rural Bangladesh. Methods A total of 219 children who reported wheezing during the previous 12 months and 122 randomly selected age‐matched individuals who had never experienced wheezing were tested for serum levels of total and specific Ascaris, Dermatophagoides pteronyssinus, alternaria and cockroach IgEs, and for intestinal helminth infection as well. Results Anti‐Ascaris IgE levels were significantly and independently associated with current wheezing during the previous 12 months [odds ratio (OR) per log_e increment is 1.31 (95% confidence interval (CI) 1.08–1.60), P=0.007], a history of at least four episodes of wheezing [OR per log_e increment is 1.52 (95% CI 1.18–1.96), P=0.001], wheezing with sleep disturbances [OR per log_e increment is 1.35 (95% CI 1.10–1.64), P=0.011] and wheezing with speech disturbances [OR per log_e increment is 1.57 (95% CI 1.19–2.08), P=0.001]. These were adjusted for gender, pneumonia history, parental asthma, Trichuris infection, use of dry leaves as fuel and other specific IgE levels. The prevalence of Ascaris infection by the presence of wheezing was not significantly different (76% vs. 72%, respectively). Conclusion We conclude that a high titre of anti‐Ascaris IgE is associated with an increased risk of asthma symptoms among 5‐year‐old rural Bangladeshi children with a high helminthic infectious load.     

Threadworms and IgE in allergic asthma

A high incidence of infection with the threadworm Enterobius vermicularis has been demonstrated in a group of children with allergic asthma, but also in a non-allergic group. There was no evidence of infection with any other helminth parasites. Presence or absence of threadworm infection was not clearly correlated with differences in total serum IgE level in either allergic or non-allergic children although levels of this immunoglobulin were raised in the former group. Some of the allergic children gave positive skin reactions following intradermal injection of an antigen extracted from E. vermicularis. The suggestion is therefore put forward that hypersensitivity to E. vermicularis allergen absorbed from the bowel might contribute to the allergic symptoms. The results are also discussed in relation to recently discovered experimental evidence that helminth infection may non-specifically potentiate unrelated IgE antibody responses.     

Ascaris sensitivity in the dog. I. Isolation and characterization of an antigen

After an infection dogs will develop a high titer of reaginic antibody to Toxocara canis, which cross reacts with an antigen from pig Ascaris suum. This report describes the purification of the Ascaris antigen by molecular sieve and ion-exchange chromatography. The end product is immuno-electrophoretically pure, with a molecular weight of 18,400; 3.46 moles of tryptophan; 4.35 of tyrosine and 5.4 of hexose per mole. The pI appears to be 5.1. The purified protein will cause an immediate hypersensitivity reaction in the skin or pulmonary system of a sensitive dog and appears to be the only such material present in the crude preparation.Unlike other preparations of Ascaris reported in the literature (Uvnas and Wold, 1967), this material has no direct mast cell degranulation properties.     

Precipitating factors in respiratory allergic disease in Indonesian children

Skin test results and IgE antibody levels measured by RAST indicate that hyper-sensitivity to house dust mite (D. pteronyssinus) is a major feature of asthma and allergic rhinitis in Indonesian children. Total serum IgE levels were higher in the allergic than in control children. 60% (twenty-one out of thirty-five) of the asthmatic children and 56% (five out of nine) of the children with allergic rhinitis had IgE antibodies to the helminth Ascaris lumbricoides compared with none out of four control children. A tendency was found for high IgE antibody levels to D. pteronyssinus to occur in association with low IgE antibody levels to A. lumbricoides and vice versa.     

Infections and allergy - helminths, hygiene and host immune regulation

There is increasing evidence that helminth infections can protect the host against Th2-mediated allergic pathologies, even though helminths themselves are strong Th2 inducers. In murine model systems, alleviation of allergy is not achieved through immune deviation to Th1, but is linked to expansion of regulatory T cell activity. Parasite infection does not prevent allergen sensitisation, but restricts the Th2 effector phase responsible for inflammation. Suppression of allergic inflammation can be transferred by Treg phenotype cells from an infected, allergen-na?ve animal to an uninfected, sensitized recipient. Patent allergy in humans is also known to be modulated by helminth infections, suggesting that a similar regulatory network may be controlling immunopathologic disease in man.     

Early infection with Trichuris trichiura and allergen skin test reactivity in later childhood

Background Allergic diseases cause a large and increasing burden in developed countries and in urban centres in middle‐income countries. The causes of this increase are unknown and, currently, there are no interventions to prevent the development of allergic diseases. The ‘hygiene hypothesis’ has tried to explain the increase through a reduction in the frequency of childhood infections causing a failure to program the immune system for adequate immune regulation. Intestinal helminth parasites are prevalent in childhood in developing countries and are associated with a lower prevalence of allergen skin test reactivity and asthma. Objectives To investigate whether children who had intestinal helminth infections during early childhood have a lower prevalence of allergen skin test reactivity later in childhood. Methods We re‐visited a population of 1055 children from whom stool samples had been collected for detection of intestinal helminth infections for another study, and collected new stool samples and performed allergen skin prick testing. Information on potential confounding variables was collected. Results Children with heavy infections with Trichuris trichiura in early childhood had a significantly reduced prevalence of allergen skin test reactivity in later childhood, even in the absence of T. trichiura infection at the time of skin testing in later childhood. Conclusion Early heavy infections with T. trichiura may protect against the development of allergen skin test reactivity in later childhood. Novel treatments to program immune‐regulation in early childhood in a way that mimics the effects of early infections with T. trichiura may offer new strategies for the prevention of allergic disease.     

The prevalence of allergic sensitisation in immigrant children in The Netherlands

BACKGROUND: Differences in the prevalence of allergic sensitisation have been reported in immigrant children living in the same urban environment. The purpose of this study is to investigate the prevalence of allergic sensitisation in school children of Dutch, Turkish and Moroccan origin. METHODS: The prevalence of sensitisation to aero-allergens was assessed using the skin prick test in a non-selected sample of 512 children (response rate 54%) living in the same inner city district of Utrecht. In addition, exhaled nitric oxide (FeNO) was determined. RESULTS: The prevalence of allergic sensitisation was dependent on the ethnic origin. As compared with Dutch children (19.1%), a higher prevalence of allergic sensitisation was observed in immigrant children for whom both parents were born in Turkey (23.6%, not significant) or Morocco (30.6%, p<0.05). The prevalence of allergic sensitisation in Dutch children was nearly 2 times lower than the reported prevalence in German children. In all sensitised children, the mean FeNO value was significantly (p<0.05) higher than in non-sensitised children, and the mean FeNO level was highest in Moroccan children sensitised to indoor allergens. CONCLUSION: In The Netherlands, immigrant children show a higher prevalence of allergic sensitisation as compared to Dutch children.     

Mycobacterium tuberculosis infection may protect against allergy in a tuberculosis endemic area

BACKGROUND: Epidemiological studies have shown an inverse relation of mycobacterial infection and the frequency of allergic diseases and asthma. Recent evidence suggests that allergic inflammation may be inhibited in the presence of chronic and persistent infections, such as that by Mycobacterium tuberculosis (MTB). The relation of tuberculin skin test (TST) size, an accepted marker of MTB infection and the frequency of allergic disease symptoms has not been reported from an area where MTB infection is endemic. OBJECTIVE: To investigate the association of TST and allergic disease symptoms, in children living in a tuberculosis (TB) endemic area. METHODS: In this cross-sectional study, 841 children aged 6-14 years from randomly selected household addresses in two poor communities of Cape Town, South Africa, were investigated with TST and standardized International Study on Asthma and Allergies in Childhood-based questionnaire on allergic disease symptoms. RESULTS: Children with positive TST (> or =10 mm) were significantly less likely to have allergic disease symptoms, in particular allergic rhinitis (AR) (adjusted odds ratio 0.43; 95% confidence interval 0.24-0.79) than those with negative TST. This association remained significant after adjusting for possible confounders and correcting for the effect of clustering (>1 child per household address) in the sample. There was a significant inverse linear trend in the relation of TST size in millimetre and the frequency of allergic disease symptoms, in particular AR (P<0.001). CONCLUSIONS: These results of inverse association of strong TST reaction and allergic disease symptoms in children from a TB endemic area are in support of the hypotheses that allergic inflammation may be inhibited by chronic infections, such as MTB.     

Reactivity and Specificity of Trichinella spiralis Fractions in Cutaneous and Serological Tests

Six diethylaminoethyl-cellulose fractions of a larval Trichinella spiralis extract, an Ascaris suum extract, and a nonrelated protein were used for cutaneous tests in guinea pigs with 8-, 14-, and 73-day-old T. spiralis infections, in guinea pigs with 13-day-old A. suum infections, and in normal guinea pigs. A selected T. spiralis fraction was used in hemagglutination (HA) tests with sera of 8 T. spiralis-infected rabbits, 41 sera of trichinellosis patients positive by bentonite agglutination tests, and 50 sera of clinically healthy persons. Immediate-type cutaneous reactions revealed extensive cross-reactivity between both parasites, although the establishment of conventional limits for considering a reaction positive allowed the specific diagnosis of acute or chronic trichinellosis with different fractions. Delayed-type reactions were specific with all fractions except one, and different fractions reacted during either the acute or the chronic phase of trichinellosis. HA detected anti-Trichinella antibodies in all the rabbits 9 to 10 days postinfection, in all trichinellosis patients, and in none of the healthy people. Correlation between HA and bentonite agglutination titers and other considerations suggest that HA with the selected fraction detects early antibodies. HA inhibition tests with A. suum extract suggest lack of HA cross-reactivity between the A. suum- and T. spiralis-selected fractions. The use of different fractions in diverse tests for clinical or epidemiological studies is suggested.     

Zur serologischen Differenzierung vonAscaris suum- undToxocara canis-Infektionen beim Schwein

Zusammenfassung Je 8 Miniaturschweine wurden mit 1500 embryonierten Eiern vonAscaris suum oderToxocara canis bzw. mit je 1000 Eiern der beiden Spulwurmarten infiziert. Seren der Tiere wurden vor der Infektion sowie 3 und 6 Wochen post infectionem mit dem ELISA in Mikrotiterplatten gegen Antigene verschiedener Entwicklungsstadien untersucht. Bei Verwendung von Extrakten adulterAscaris undToxocara als Antigene waren sowohl bei den infizierten als auch bei den nichtinfizierten Kontrollen deutliche Reaktionen nachweisbar. Antigene aus embryonierten Eiern bzw. Larven beider Askaridenarten erzeugten nur bei den infizierten Tieren deutliche positive Reaktionen einschließlich bei den heterolog infizierten Schweinen, jedoch nicht bei den nicht infizierten Kontrolltieren.Nach Absättigung der Seren mit den jeweils heterologen Antigenen konnten mit homologen Antigenextrakten deutliche Antikörperreaktionen nachgewiesen werden. Auf diese Weise gelang es, Infektionen mit den beiden Nematodenarten serologisch zu differenzieren.

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Serological differentiation ofAscaris suum andToxocara canis infections in pigs

Groups of eight miniature pigs were infected either with 1,500 embryonated eggs each ofAscaris suum orToxocara canis or with 1,000 eggs each of both nematodes. Sera were sampled before the infection as well as three and six weeks postinfection and then investigated in the ELISA on microtitre plates against antigens of various developmental stages. When extracts of adultAscaris andToxocara worms were used as antigens, distinct reactions were registered both in the infected and in the uninfected control groups. Antigens isolated from either embryonated eggs or larvae of both worms produced distinctly positive reactions with sera of the infected animals, including those pigs with heterologous infections but not with sera from uninfected controls. After saturation with heterologous antigens, the sera showed distinct antibody reactions against homologous antigen extracts and in this way infections with the two nematode species could be serologically differentiated.

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Herrn Prof. Dr. G. Piekarski zum 70 Geburtstag giwidmet     

The tropics,helminth infections and hygiene hypotheses

The Tropics is very appropriate to test the hypotheses raised to explain the increasing trends of allergy and other inflammatory diseases worldwide. The absence of parasite infection as a possible cause of the increase of allergic diseases was proposed by J. Gerrard a long time ago; however, the idea that helminth infections, which induce a strong Th2 could reduce allergy symptoms seems counterintuitive; but the fact is that they have a dual effect: they increase the Th2 responses but also exert immunosuppression and both effects influence the symptoms of allergy. Basic experimentation has provided valuable information about the mechanisms of allergic inflammation and more recently, about its control by helminth induced immunomodulation, discovering helminth molecules with anti-inflammatory properties that are meant to replace the live helminth therapeutic approaches. The immunosuppressive power of helminths makes them excellent candidates to be considered in the hygiene hypotheses. Future comprehensive studies evaluating simultaneously the role of microbial infections, helminth infections, microbiota, pollution and biodiversity will help to elucidate the causes of the increasing trends of allergic disorders. Doing this in the tropics, where all these variables are still present could be difficult but no doubt that will be more informative.     

Respiratory responses to Ascaris antigen in rhesus and cynomolgus monkeys

Responses to Ascaris antigen were evaluated in rhesus and cynomolgus monkeys. Of 19 cynomolgus monkeys tested, 15 were found to have cutaneous reactivity to Ascaris: 13 of these responded to Ascaris aerosols with changes in respiratory function including an increase in respiration rate, decrease in tidal volume and peak expiratory flow rate, decrease in dynamic compliance, and an increase in resistance. Four of the six rhesus monkeys studied with cutaneous reactivity to Ascaris responded to Ascaris aerosols: the changes in respiratory function observed after the Ascaris challenge in these monkeys were similar to those observed in the cynomolgus monkeys. Responses to repetitive Ascaris challenges were obtained in monkeys of both species with a recovery period of 30 to 60 min between challenges. In monkeys of both species that reacted to Ascaris aerosols, blood pressure was elevated transiently; changes in heart rate were variable. Changes in cardiovascular measurements were not observed in monkeys that did not respond to Ascaris aerosols. Thus, it appears that the cynomolgus monkey responds to an aerosol Ascaris challenge in a manner similar to the rhesus monkey and is an additional suitable model for the study of allergic respiratory responses.     

Concurrent infection with an intestinal helminth parasite impairs host resistance to enteric Citrobacter rodentium and enhances Citrobacter-induced colitis in mice

Infections with intestinal helminth and bacterial pathogens, such as enteropathogenic Escherichia coli, continue to be a major global health threat for children. To test the hypothesis that intestinal helminth infection may be a risk factor for enteric bacterial infection, a murine model was established by using the intestinal helminth Heligomosomoides polygyrus. To analyze the modulatory effect of a Th2-inducing helminth on the outcome of enteric bacterium Citrobacter rodentium infection, BALB/c and STAT 6 knockout (KO) mice were infected with H. polygyrus, C. rodentium, or both. We found that only BALB/c mice coinfected with H. polygyrus and C. rodentium displayed a marked morbidity and mortality. The enhanced susceptibility to C. rodentium and intestinal injury of coinfected BALB/c mice were shown to be associated with a significant increase in helminth-driven Th2 responses, mucosally and systemically, and correlated with a significant downregulation of protective gamma interferon and with a dramatic upregulation of the proinflammatory tumor necrosis factor alpha response. In addition, C. rodentium-associated colonic pathology in coinfected BALB/c mice was significantly enhanced, whereas bacterial burden was increased and clearance was delayed. In contrast, coinfection in STAT 6 KO mice failed to promote C. rodentium infection or to induce a more severe intestinal inflammation and tissue injury, demonstrating a mechanism by which helminth influences the development of host protective immunity and susceptibility to bacterial infections. We conclude that H. polygyrus coinfection can promote C. rodentium-associated disease and colitis through a STAT 6-mediated immune mechanism.     

Suppression of type 2 immunity and allergic airway inflammation by secreted products of the helminth Heligmosomoides polygyrus

Allergic asthma is less prevalent in countries with parasitic helminth infections, and mice infected with parasites such as Heligmosomoides polygyrus are protected from allergic airway inflammation. To establish whether suppression of allergy could be mediated by soluble products of this helminth, we tested H. polygyrus excretory‐secretory (HES) material for its ability to impair allergic inflammation. When HES was added to sensitising doses of ovalbumin, the subsequent allergic airway response was suppressed, with ablated cell infiltration, a lower ratio of effector (CD4⁺CD25⁺Foxp3^?) to regulatory (CD4⁺Foxp3⁺) T (Treg) cells, and reduced Th1, Th2 and Th17 cytokine production. HES exposure reduced IL‐5 responses and eosinophilia, abolished IgE production and inhibited the type 2 innate molecules arginase‐1 and RELM‐α (resistin‐like molecule‐α). Although HES contains a TGF‐β‐like activity, similar effects in modulating allergy were not observed when administering mammalian TGF‐β alone. HES also protected previously sensitised mice, suppressing recruitment of eosinophils to the airways when given at challenge, but no change in Th or Treg cell populations was apparent. Because heat‐treatment of HES did not impair suppression at sensitisation, but compromised its ability to suppress at challenge, we propose that HES contains distinct heat‐stable and heat‐labile immunomodulatory molecules, which modulate pro‐allergic adaptive and innate cell populations.     

The role of parasitic infections in atopic diseases in rural schoolchildren

BACKGROUND: There is increasing evidence that the farming environment has a protective effect as regards allergic diseases. Exposure to animal parasites, particularly helminth infections, is common in the farming environment. However, the role of helminths in this environment is not well determined to date. METHODS: This analysis focuses on 613 children 6-13 years of age from rural areas of Austria, Germany and Switzerland, who took part in the Allergy and Endotoxin (ALEX) study. Allergic diseases and farming characteristics were assessed by a standardized questionnaire and as a crude measure of possible exposure to helminths, IgG antibodies to Ascaris lumbricoides were measured. RESULTS: Exposure to nematodes, as determined by the levels of antibody to A. lumbricoides, was more frequent among farmers' children than non-farmers' children (39.8%vs 31.1%, P = 0.03). This positive serology was found to be significantly associated with high total IgE levels [odds ratio (OR) = 3.05, 95% confidence interval (CI) = 1.81-5.12] and eosinophilia (OR = 2.84, 95% CI = 1.66-4.84). However, no association between anti-nematode serology and the prevalences of asthma, wheeze, hay fever or atopy was found. A weak association for atopy was observed after adjustment for total IgE. CONCLUSION: Immunoglobulin G antibodies to A. lumbricoides, as a crude measure of possible exposure to helminths, did not indicate any protective effect against allergic diseases in this population. Although farmers' children had increased antibody levels reactive to helminth parasites indicating exposure, this did not explain the protective effect of farming against atopic diseases.     

Eosinophilic Pneumonias

Summary: This review starts with discussions of several infectious causes of eosinophilic pneumonia, which are almost exclusively parasitic in nature. Pulmonary infections due specifically to Ascaris, hookworms, Strongyloides, Paragonimus, filariasis, and Toxocara are considered in detail. The discussion then moves to noninfectious causes of eosinophilic pulmonary infiltration, including allergic sensitization to Aspergillus, acute and chronic eosinophilic pneumonias, Churg-Strauss syndrome, hypereosinophilic syndromes, and pulmonary eosinophilia due to exposure to specific medications or toxins.     

Novel T‐cell epitopes on Schistosoma japonicum SjP40 protein and their preventive effect on allergic asthma in mice

Allergic asthma is a chronic inflammatory disease mediated by Th2 cell immune responses. Currently, immunotherapies based on immune deviation are attractive, preventive, and therapeutic strategies for asthma. Many studies have shown that intracellular bacterial infections such as mycobacteria and their components can suppress asthmatic reactions by enhancing Th1 responses, while helminth infections and their proteins can inhibit allergic asthma via immune regulation. However, some helminth proteins such as SmP40, the major egg antigen of Schistosoma mansoni, are found as Th1 type antigens. Using a panel of overlapping peptides, we identified T‐cell epitopes on SjP40 protein of Schistosoma japonicum, which can induce Th1 cytokine and inhibit the production of Th2 cytokines and airway inflammation in a mouse model of allergic asthma. These results reveal a novel form of immune protective mechanism, which may play an important role in the modulating effect of helminth infection on allergic asthmatic reactions.