Impact of Enterobius vermicularis infection and mebendazole treatment on intestinal microbiota and host immune response.

BACKGROUND: Previous studies on the association of enterobiasis and chronic inflammatory diseases have revealed contradictory results. The interaction of Enterobius vermicularis infection in particular with gut microbiota and induced immune responses has never been thoroughly examined. METHODOLOGY/FINDINGS: In order to answer the question of whether exposure to pinworm and mebendazole can shift the intestinal microbial composition and immune responses, we recruited 109 (30 pinworm-negative, 79 pinworm-infected) first and fourth grade primary school children in Taichung, Taiwan, for a gut microbiome study and an intestinal cytokine and SIgA analysis. In the pinworm-infected individuals, fecal samples were collected again at 2 weeks after administration of 100 mg mebendazole. Gut microbiota diversity increased after Enterobius infection, and it peaked after administration of mebendazole. At the phylum level, pinworm infection and mebendazole deworming were associated with a decreased relative abundance of Fusobacteria and an increased proportion of Actinobacteria. At the genus level, the relative abundance of the probiotic Bifidobacterium increased after enterobiasis and mebendazole treatment. The intestinal SIgA level was found to be lower in the pinworm-infected group, and was elevated in half of the mebendazole-treated group. A higher proportion of pre-treatment Salmonella spp. was associated with a non-increase in SIgA after mebendazole deworming treatment. CONCLUSIONS/SIGNIFICANCE: Childhood exposure to pinworm plus mebendazole is associated with increased bacterial diversity, an increased abundance of Actinobacteria including the probiotic Bifidobacterium, and a decreased proportion of Fusobacteria. The gut SIgA level was lower in the pinworm-infected group, and was increased in half of the individuals after mebendazole deworming treatment.

Worm infestations and development of autoimmunity in children - The ABIS study.

Worm infestations influence the immune system and may therefore decrease the risk for autoimmune diseases. The aim of the study was to determine whether children who have developed autoimmune disease were less likely to have had worm infestations in childhood. The ABIS-study is a prospective population-based cohort study of children born in southeast Sweden 1997/99. 17.055 children participated. As of June 2014 116 individuals had developed Type 1 diabetes, 181 celiac disease, and 53 Juvenile Rheumatoid Arthritis. The parents answered questions on worm infestations when the children were 1, 5 and 8 years of age. The ABIS registry was connected to the National Registry of Drug Prescriptions, and national registries for diagnosis of the studied diseases. We found no differences in incidence of worm infestations at 1, 5 or 8 years of age between children who developed autoimmune disease(s) or healthy controls. At 8 years in total 20.0% of the general child population had experienced a worm infestation; children who developed Type 1 diabetes, 21,3%, celiac disease 19,5% and JRA 18,8%. There was no difference in prescriptions of drugs for treatment of worm infestations between those who had and who had not developed Type 1 diabetes, celiac disease, Juvenile Rheumatoid Arthritis. We found no associations indicating that worm infestations in childhood does not play a role in the development of autoimmune diseases in Sweden.

Immune responses in children infected with the pinworm Enterobius vermicularis in central Greece.

Previous studies have suggested an immunomodulatory and even protective role for Enterobius vermicularis, the least pathogenic human intestinal helminth. Here, in a study using haematological and serological parameters, we tested a total of 215 children from central Greece, with a mean age of 8.39, of whom 105 (48.84%) were infected with E. vermicularis and 110 (51.16%) were matched healthy controls. In particular, we analysed eosinophil counts (EO), serum eosinophil cationic protein (ECP), total and specific serum immunoglobulin E (IgE) and the ECP/EO ratio. The atopic status and the potential occurrence of clinically expressed allergic diseases were both taken into account. Eosinophils, ECP and IgE were found to be higher in infected than in uninfected children, indicating a type-2 immune response activation during infection. Atopic infected children exhibited higher IgE levels compared to non-atopic ones. EO and ECP were found to be lower in atopic children who had a history of allergic disease than in those with no such history. The type-2 oriented immune response elicited against E. vermicularis could contribute to a balanced activation of the immune system in the examined children. Interestingly, although the atopic children showed a stronger activation, they did not exhibit any symptoms and, moreover, there seemed to be some indication of immunosuppression in those children with a positive history of allergic disease.

Strain-related effects of fenbendazole treatment on murine experimental autoimmune encephalomyelitis.

Parasitic infections are a concern in animal facilities, in view of their influence on physiological processes and the immune status of animals. Pinworms are effectively controlled with the anthelminthic fenbendazole (FBZ, [5-(phenylthio)-1H-benzamidazol-2-yl]carbamic acid methyl ester; C(15)H(13)N(3)O(2)S); however, questions remain as to whether prolonged FBZ exposure alters the disease course in specific experimental models, such as those pertaining to the immune system. We report that a three-month regimen of FBZ-medicated feed severely affected the onset and disease severity of murine experimental autoimmune encephalomyelitis (EAE), a disease that mimics multiple sclerosis. Differences were recorded between mouse strains used. Our data suggest that where the use of FBZ is mandatory, its full effect should be verified on the particular EAE variant adopted by the laboratory.

At homeostasis filarial infections have expanded adaptive T regulatory but not classical Th2 cells.

Despite the well-documented immune suppression associated with human helminth infections, studies characterizing the immune response at the single-cell level are scanty. We used multiparameter flow cytometry to characterize the type of effector (Th1, Th2, and Th17) and regulatory (natural T regulatory cells [nTregs] and adaptive Treg cells [aTreg/type 1 regulatory cells (Tr1s)]) CD4(+) and CD8(+) T cells in filaria-infected (Fil(+)) and -uninfected (Fil(-)) individuals at homeostasis (in the absence of stimulation). Frequencies of CD4(+) lymphocytes spontaneously producing IL-4, IL-10, and IL-17A were significantly higher in Fil(+), as were those of IL-10(+)/IL-4(+) double-producing CD4(+) cells. Interestingly, frequencies of Th17 and aTreg/Tr1s but not classical Th1 or Th2 cells were significantly increased in Fil(+) compared to Fil(-) individuals. Although the frequency of nTreg was increased in Fil(+), IL-10 was overwhelmingly produced by CD4(+)CD25(-) cells. Moreover, the concentration of IL-10 produced spontaneously in vitro strongly correlated with the integrated geometric mean fluorescence intensity of IL-10-producing aTreg/Tr1s in Fil(+). Together, these data show that at steady state, IL-10-producing aTreg/Tr1 as well as nTreg and effector Th17 CD4(+) cells are expanded in vivo in human filarial infections. Moreover, we have established baseline ex vivo frequencies of effector and Tregs at homeostasis at a population level.

Effects of fenbendazole on the murine humoral immune system.

Pinworms are highly contagious parasites that have been effectively treated in laboratory rodents with fenbendazole (FBZ). Whether FBZ has any detrimental side effects that may compromise experimental results is unknown. Here we asked whether the immune systems from young and aged mice are altered under FBZ treatment. We compared control and FBZ-treated groups of young (age, 2 to 4 mo) and old (age, 22 to 24 mo) BALB/cN mice. The treated mice received a total of 4 wk (alternating-week treatment regimen) of FBZ-medicated feed. Spleen and bone marrow were collected for immunologic assays, and heart, stomach, intestines, kidneys, and liver were evaluated by histopathology. Our results indicate that FBZ treatment has significant effects on the immune systems of mice; these effects are greater in aged mice. FBZ treatment adversely affected mRNA and protein expression of E2A (a transcription factor crucial for B lymphocytes) in activated precursor B lymphocytes obtained from the bone marrow of young and old mice. These effects were reversed by 6 wk on regular feed after the end of treatment. Activated B lymphocytes from the spleens of young and old mice showed decreased function (cell proliferation, E2A mRNA and protein expression) through the last time point of FBZ treatment but recovered by 2 to 4 wk after treatment. Our findings suggest that FBZ treatment may alter sensitive immune and molecular measures as presented here, and postponing the experimental use of mice until at least 6 wk after treatment should be considered.

Infection with Syphacia obvelata (pinworm) induces protective Th2 immune responses and influences ovalbumin-induced allergic reactions.

Infections with pinworms are common in rodent animal facilities. In this study, we show the consequence of an outbreak in a transgenic barrier facility of infection by Syphacia obvelata, a murine pinworm gastrointestinal nematode. Immune responses were defined in experimental infection studies with BALB/c mice. Infection with S. obvelata induced a transient Th2-type immune response with elevated interleukin 4 (IL-4), IL-5, and IL-13 cytokine production and parasite-specific immunoglobulin G1 (IgG1). In contrast, BALB/c mice deficient in IL-13, IL-4/13, or the IL-4 receptor alpha chain showed chronic disease, with a >100-fold higher parasite burden, increased gamma interferon production, parasite-specific IgG2b, and a default Th2 response. Interestingly, infected IL-4-/- BALB/c mice showed only slightly elevated parasite burdens compared to the control mice, suggesting that IL-13 plays the dominant role in the control of S. obvelata. The influence that pinworm infection has on the allergic response to a dietary antigen was found to be important. Helminth-infected mice immunized against ovalbumin (Ova) elicited more severe anaphylactic shock with reduced Ova-specific IL-4 and IL-5 than did noninfected controls, demonstrating that S. obvelata infection is able to influence nonrelated laboratory experiments. The latter outcome highlights the importance of maintaining mice for use as experimental models under pinworm-free conditions.

Pelvic pain caused by intraperitoneal Enterobius vermicularis (threadworm) ova with an associated systemic autoimmune reaction.

AIM: The aim of this paper, based on a case study was two-fold; firstly to review the sites and gynecologic complications of ectopic Enterobius vermicularis and secondly study the autoimmune accompaniments of parasitic infestations. METHODS: A case of intraperitoneal ectopic Enterobius vermicularis, with accompanying autoimmune signs and symptoms, is presented and its response to surgical and medical treatment described. A medical literature search was carried out into the subject of ectopic Enterobius vermicularis, particularly from the gynecologic perspective along with a study of autoimmune activation associated with parasitic infestation. RESULTS: Pelvic pain was found to be caused by chronic inflammation from ectopic Enterobius vermicularis. This was treated both surgically and medically, with the surgical treatment proving to be inadequate but with a good response to immune modification. In the literature ectopic Enterobius vermicularis was found to be treatable surgically. CONCLUSION: Ectopic Enterobius vermicularis was found to create symptomatic inflammatory lesions that could be treated surgically and an associated autoimmune response treatable by immune modification.

Negative association of Enterobius infestation with asthma and rhinitis in primary school children in Taipei.

BACKGROUND: The relationship between allergy and parasites has been controversial, especially in non-tropical countries. Enterobius vermicularis (human pinworm) is the most prevalent intestinal parasite in industrialized countries. OBJECTIVE: To examine the association between pinworm infestation and allergy in primary school children. METHOD: Peri-anal tape test for pinworm is routinely performed in Taipei primary schools. We collected data from school records and questionnaires distributed to all children in four primary schools grades 1 through 6 (n = 3107). RESULTS: The prevalence of physician-diagnosed asthma (9.3% vs. 14.1%, P = 0.007) and allergic rhinitis (27.4% vs. 38.3%, P = 0.001) was lower in pinworm-positive compared to uninfested children. Pinworm was not correlated with atopic dermatitis or parent allergy. With logistic regression controlling for sex, parent allergy and lower respiratory infection, current asthma (OR = 0.25, 95% CI 0.10-0.63) and rhinitis (OR = 0.61, 95% CI 0.45-0.84) were negatively associated with pinworm. Among children in grades 3-6 who had no asthma or rhinitis before age 7, those with early infestation (pinworm diagnosis at or before grade 1) had a lower risk of having diagnosis of rhinitis during school years, compared to the uninfected group (5.4% vs. 12.3%, P = 0.03; adjusted OR = 0.47, 95% CI 0.21-1.02). CONCLUSIONS: We identified a negative association between pinworm infestation and allergic airway diseases, which could in part be attributed to protective effect of pinworm infestation on development of allergic symptoms. Other mechanisms of association could not be ruled out.

Susceptibility of natural hybrids between house mouse subspecies to Sarcocystis muris.

A previous study showed that the susceptibility of hybrids between two Mus musculus musculus and Mus musculus domesticus did not apply to every parasite. The authors proposed that only parasites which exerted enough constraints would induce the selection of poorly compatible systems of resistance in the subspecies. This study completes the previous work. Experimental infections of mice of the two subspecies and their hybrids with the tissue-dwelling protozoan Sarcocystis muris show that hybrids are more susceptible to the coccidian than M. m. musculus and M. m. domesticus individuals. This result demonstrates that the hybrids are not only susceptible to intestinal helminths, and confirms the 'constraint hypothesis'.

Allergic disease and the infestation of Enterobius vermicularis in Swedish children 4-10 years of age.

BACKGROUND: The possible association between certain childhood infections and the propensity to develop allergic disease may include intestinal helminth infections. The experiences of such associations derive mainly from studies in tropical areas, and the results are not clear-cut. OBJECTIVE: To explore the association between Enterobius vermicularis and allergic disease in Swedish children 4 to 10 years of age. METHOD: The occurrence of E. vermicularis was examined by perianal tape tests in 70 allergic children recovered from a pediatric register of positive skin-prick tests. A nonallergic control group (n = 102) was gathered from a cohort of children previously examined for the prevalence of E. vermicularis and allergic symptoms. RESULTS: In the allergic group 26 of the 70 cases (37%) had a positive tape-test for E. vermicularis, compared to 23 of the 102 cases (23%) in the nonallergic control group (p = .037). CONCLUSION: The results indicate that E. vermicularis could be more frequent in children with allergic disease as defined by allergic symptoms and a positive skin-prick test compared to nonallergic children, i. e., those without a history of allergic disease. These data, however, do not allow any conclusion on the nature of the possible association between E. vermicularis and allergic disease.

[New approaches to the eradication of enterobiasis in children]. / Novye podkhody k ozdorovleniiu detei ot énterobioza.

The paper outlines the results of studies dealt with the detection of risk factors and groups for enterobiasis, the efficiency of the treatment of children suffering from the disease with medamine, biologicals, and Normase. It is shown that risk factors may include an abnormal course of antenatality, minor developmental malformations (diastema, dystrophy, abnormalities of the eye, hand, foot, etc.), as well as early artificial feeding of babies (before they reach 3 months of life). Enterobiasis is found to have a negative influence on the physical, nervous, and mental development and suppression of non-specific immunity in children, which is suggested by the reduction in salivary lysozyme activity, which is lower than the normal level and on blood alpha-interferon production. There is strong evidence for the considerable immunosuppressive effects of enterobiasis on the formation of a postvaccinal immunity against measles. When given in a single course dose, medamine shows a 100% efficiency in the treatment of enterobiasis. Moreover, bificol, bifidumbacterin, and Normase may be useful to enhance the treatment efficiency and children's recovery from enterobiasis.