Worldwide overview of human infections with Hymenolepis diminuta.

Hymenolepis diminuta is a zoonotic cestode parasitizing the small intestine of rodents (definitive hosts). Humans can accidentally enter into the life cycle of this tapeworm via the ingestion of infected insects (intermediate hosts) containing cestode cysticercoids in their body cavity. More than two centuries after the first record in humans, there are no accurate estimates of the number of human cases around the world. In order to have a more precise idea about the number of human cases with H. diminuta and the current status of the disease (hymenolepiasis) worldwide, we conducted a literature review of published records on human infection with H. diminuta. One thousand five hundred and sixty-one published records of infection with H. diminuta from 80 countries were identified. This review presents an estimate of the number of human cases with H. diminuta and a current overview of the prevalence, geographic distribution, symptoms, diagnosis, exposure to infective stages, and therapeutic approaches for this underestimated zoonotic tapeworm.

Morphological, Molecular, and Pathological Appraisal of Hymenolepis nana (Hymenolepididae) Infecting Laboratory Mice (Mus musculus).

Hymenolepis nana, typically a parasite found in conventionally established mouse colonies, has zoonotic potential characterized by autoinfection and direct life cycle. The objective of this study was to determine the rate of parasite infection in laboratory mice. The hymenolepidide cestode infected 40% of the 50 mice sampled. The rate of infection in males (52%) was higher than in females (28%). Morphological studies on the cestode parasite showed that worms had a globular scolex with four suckers, a retractable rostellum with 20-30 hooks, and a short unsegmented neck. In addition, the remaining strobila consisted of immature, mature, and gravid proglottids, irregularly alternating genital pores, lobulated ovaries, postovarian vitelline glands, and uteri with up to 200 eggs in their gravid proglottids. The parasite taxonomy was confirmed by using molecular characterization based on the sequence analysis of the mitochondrial cytochrome c oxidase subunit 1 (mtCOX1) gene. The parasite recovered was up to 80% identical to other species in GenBank. High blast scores and low divergence were noted between the isolated parasite and previously described H. nana (gb| AP017666.1). The phylogenetic analysis using the COX1 sequence places this hymenolepidid species of the order Cyclophyllidea.

The immune response to Hymenolepis nana in mice decreases tumorigenesis induced by 7,12 dimethylbenz-anthracene.

BACKGROUND: Cancer is a high-impact disease throughout the world. A negative correlation has been established between the development of cancer and the Th2 immune response. Infection by helminth parasites is characterized by the induction of a strong and long-lasting Th2 response. The aim of this work was to evaluate the effect of the immune response induced by the infection with the helminth Hymenolepis nana, on the tumorigenesis induced by dimethylbenz-anthracene (DMBA) in mice. METHODOLOGY: Four different groups of 14 female BALB/c mice were formed; Group A, dimethyl sulfoxide (DMSO) (vehicle) was administered cutaneously, Group B infected with H. nana, group C, cutaneously DMBA and finally Group D infected with H. nana and cutaneous DMBA. The tumor load was determined in those animals that developed cancerous lesions. In all groups were determined: serum concentration of IgE, IFNγ, IL-10, IL-5 and malondialdehyde (MDA). The inflammatory infiltrate was analyzed from skin samples and the expression of the main eosinophilic protein and myeloperoxidase was determined. RESULTS: The group previously infected with H. nana had a reduced amount of tumors with smaller size, in comparison to the group that received only DMBA; this reduction was associated with lower levels of IFNγ and IL-10, while levels of IgE, IL-5 and MDA were higher. Further, the number of eosinophils and neutrophils was statistically higher in the animals that were previously infected with the helminth and developed less tumors. CONCLUSION: The immune response induced by H. nana infection is associated with the reduction of tumors probably due to the activity of eosinophils and neutrophils.

Selected Molecular Mechanisms Involved in the Parasite⁻Host System Hymenolepis diminuta⁻Rattus norvegicus.

The rat tapeworm Hymenolepis diminuta is a parasite of the small intestine of rodents (mainly mice and rats), and accidentally humans. It is classified as a non-invasive tapeworm due to the lack of hooks on the tapeworm's scolex, which could cause mechanical damage to host tissues. However, many studies have shown that metabolites secreted by H. diminuta interfere with the functioning of the host's gastrointestinal tract, causing an increase in salivary secretion, suppression of gastric acid secretion, and an increase in the trypsin activity in the duodenum chyme. Our work presents the biochemical and molecular mechanisms of a parasite-host interaction, including the influence on ion transport and host intestinal microflora, morphology and biochemical parameters of blood, secretion of antioxidant enzymes, expression of Toll-like receptors, mechanisms of immune response, as well as the expression and activity of cyclooxygenases. We emphasize the interrelations between the parasite and the host at the cellular level resulting from the direct impact of the parasite as well as host defense reactions that lead to changes in the host's tissues and organs.

The inflammatory effect of infection with Hymenolepis diminuta via the increased expression and activity of COX-1 and COX-2 in the rat jejunum and colon.

The aim of this study was to determine whether Hymenolepis diminuta may affect the expression and activity of cyclooxygenase 1 (COX-1) and cyclooxygenase 2 (COX-2), resulting in the altered levels of their main products - prostaglandins (PGE2) and thromboxane B2 (TXB2). The study used the same experimental model as in our previous studies in which we had observed changes in the transepithelial ion transport, tight junctions and in the indicators of oxidative stress, in both small and large intestines of rats infected with H. diminuta. In this paper, we investigated not only the site of immediate presence of the tapeworm (jejunum), but also a distant site (colon). Inflammation related to H. diminuta infection is associated with the increased expression and activation of cyclooxygenase (COX), enzyme responsible for the synthesis of PGE2 and TXB2, local hormones contributing to the enhanced inflammatory reaction in the jejunum and colon in the infected rats. The increased COX expression and activity is probably caused by the increased levels of free radicals and the weakening of the host's antioxidant defense induced by the presence of the parasite. Our immunohistochemical analysis showed that H. diminuta infection affected not only the intensity of the immunodetection of COX but also the enzyme protein localization within intestinal epithelial cells - from the entire cytoplasm to apical/basal regions of cells, or even to the nucleus.

Malignant Transformation of Hymenolepis nana in a Human Host.

Neoplasms occur naturally in invertebrates but are not known to develop in tapeworms. We observed nests of monomorphic, undifferentiated cells in samples from lymph-node and lung biopsies in a man infected with the human immunodeficiency virus (HIV). The morphologic features and invasive behavior of the cells were characteristic of cancer, but their small size suggested a nonhuman origin. A polymerase-chain-reaction (PCR) assay targeting eukaryotes identified Hymenolepis nana DNA. Although the cells were unrecognizable as tapeworm tissue, immunohistochemical staining and probe hybridization labeled the cells in situ. Comparative deep sequencing identified H. nana structural genomic variants that are compatible with mutations described in cancer. Invasion of human tissue by abnormal, proliferating, genetically altered tapeworm cells is a novel disease mechanism that links infection and cancer.

Some studies on spontaneous Hymenolepis diminuta infection in laboratory rats.

Hymenolepis diminuta is a tapeworm that occurs worldwide. It is known to be found commonly in areas where large amounts of food grains or other dry feed products, which are the favorite foods for rats. Transmission of disease to human is uncommon; however, it may be a serious threat for population who are living in rural areas which are suffering from excessive rodents. Here, this study had done on spontaneous H. diminuta infection in laboratory rats as a model. Out of thirty five adult laboratory rats investigated for parasitic diseases only nine (25.71%) were diagnosed positive for spontaneous H. diminuta infection. Four of them (44.44%) were found losing of weight and lacking of motility, while the others were normal. On microscopic examination, H. diminuta eggs had been found in their stool. On autopsy, small intestines were found to contain from 5-6 multi-segmented tapeworms in each rat. Histopathologically, intestinal lumen showed varying sections of H. diminuta segments with serrated borders. H. diminuta infection caused multiple mucosal ulcers with absence of intestinal villi from the surface epithelium and excessive mucin. Moreover, inflammatory cells infiltration in the connective tissue core of the villi. Furthermore, the Toluidine blue stain showed that there are Mastiocytosis. Additionally, there were goblet cells hyperplasia on using PAS. Moreover, there were high expression of cyclooxygenase 2 (COX-2), tumor necrosis factor-α (TNF-α) and inducible Nitric-Oxide Synthase (iNOs). This implicate, strong correlation between COX-2, TNF-α and iNOs expression and inflammation induced by H. diminuta.

Murine autoimmune arthritis is exaggerated by infection with the rat tapeworm, Hymenolepis diminuta.

Infection with helminth parasites triggers strong and stereotypic immune responses in humans and mice, which can protect against specific experimentally-induced autoimmune diseases. We have shown that infection with the rat tapeworm, Hymenolepis diminuta, confers a protective effect on FCA-induced joint inflammation. Here, we investigated the effect of a prophylactic infection with H. diminuta on the K/BxN-serum model of polyarthritis in BALB/c mice. Mice were infected with 10 cysticercoids of H. diminuta by oral gavage and 8 days later arthritis was induced by i.p. injection of K/BxN arthritogenic serum. Joint swelling and pain measurements were recorded throughout a 13 day time course. At necropsy, joints and blood serum were collected. K/BxN-treated mice developed joint inflammation in the front paws, hind paws and knees as shown by increased swelling, mechanical allodynia and myeloperoxidase activity. Mice infected with H. diminuta had more severe disease, with increased eosinophil peroxidase activity in their paws and greater inflammatory infiltrate and synovitis in the knee joints. Hymenolepis diminuta-infected mice displayed significant increases in serum levels of C5a and mast cell protease-1 compared with K/BxN-serum only treatment, the latter being indicative of mast cell activation. In contrast to the protective effect of infection with H. diminuta in FCA-induced monoarthritis, infection with this helminth exacerbated K/BxN serum-induced polyarthritis in BALB/c mice. This correlated with increases in C5a and mast cell activation: factors critical in the development of K/BxN-induced arthritis. Thus, while data accumulate from animal models showing that infection with helminth parasites may be beneficial for a variety of auto-inflammatory diseases, our findings demonstrate the potential for helminths to exacerbate disease. Hence care is needed when helminth therapy is translated into a clinical setting.

Histopathological changes in small and large intestines during hymenolepidosis in rats.

The tapeworm Hymenolepis diminuta is a chronic parasite living in the small intestine of rats, mice and humans. The aim of this study was to determine histopathological changes in the rat intestine during experimental hymenolepidosis. Our results showed that in rats infected with H. diminuta slight changes occurred in the length of the villus and crypts in different parts of the digestive tract. The changes were most distinct in the duodenum and jejunum on the 16 days post H. diminuta infection.

Exacerbation of oxazolone colitis by infection with the helminth Hymenolepis diminuta: involvement of IL-5 and eosinophils.

Substantial data show that infection with helminth parasites ameliorates colitis; however, oxazolone-induced colitis is exaggerated in mice infected with the tapeworm, Hymenolepis diminuta. We tested the hypothesis that the IL-5 response to helminth infection enhances the severity of oxazolone-induced colitis. Mice were infected with H. diminuta and 8 days later were treated with oxazolone ± anti-IL-5 antibodies. Colitis was assessed 72 hours postoxazolone treatment by disease activity scores, myeloperoxidase activity, and histopathology. Other mice received injections of a replication-deficient adenovirus that carried the IL-5 (Ad.IL-5) gene or a control adenovirus (Ad.delete) ± oxazolone. The effect of H. diminuta+oxazolone in CCL11/CCL22 (eotaxin-1 and 2) knockout (KO) mice was determined. Helminth infection and Ad.IL-5 treatment increased IL-5 and eosinophil numbers. In vivo neutralization of IL-5 significantly reduced the severity of colitis in H. diminuta+oxazolone-treated mice, and H. diminuta did not exaggerate oxazolone-induced colitis in CCL11/CCL22 KO mice. Mice receiving Ad.IL-5 only had no colitis, while oxazolone-induced colitis was more severe in animals cotreated with Ad.IL-5 (Ad.delete + oxazolone was not significantly different from oxazolone only). Thus, while there is much to be gleaned about antiinflammatory mechanisms from rodent-helminth model systems, these data illustrate the caveat that infection with helminth parasites as a therapy could be contraindicated in patients with eosinophilia or elevated IL-5 unless coupled to appropriate measures to block IL-5 and/or eosinophil activity.

A human case of Hymenolepis diminuta in a child from eastern Sicily.

We report a case of Hymenolepis diminuta infection in a 2-year-old child living in a suburban area of Catania, Italy. This case was initially referred to us as Dipylidium caninum infection, which was not cured after being treated twice with mebendazole. However, by analyzing the clinical presentation and stool samples we arrived to the diagnosis of H. diminuta infection. The case presented with atypical allergic manifestations which had never been reported as clinical features of symptomatic H. diminuta infection; remittent fever with abdominal pain, diffuse cutaneous itching, transient thoracic rash, and arthromyalgias. The patient was treated with a 7-day cycle of oral niclosamide, which proved to be safe and effective. This case report emphasizes that a correct parasitological diagnosis requires adequate district laboratories and trained personnel. In addition, we recommend the importance of reporting all H. diminuta infection cases, in order to improve knowledge on epidemiology, clinical presentation, and treatment protocols.

Food additives and Hymenolepis nana infection: an experimental study.

The effect of sodium benzoate (SB) on the pathogenesis of Hymenolepis nana (H. nana) and its neurological manifestations was studied in the present work. One hundred and thirty five mice were classified into three groups. GI: received SB alone. GII: received SB before & after infection with H. nana and GIII: infected with H. nana. All groups were subjected to parasitological, histopathological, immunohistochemical and biochemical assays. The results revealed a significant decrease in IL-4 serum level with a significant increase in gamma amino butyric acid (GABA) and decrease in zinc brain levels in GI, while GII showed non significant increase in IL-4 level that resulted in a highly significant increase in the mean number of cysticercoids and adult worms with delayed expulsion as compared to GIII. This was reflected on histopathological and immunohistochemical changes in the brain. Also, there was a highly significant increase in GABA and decrease in zinc brain levels in GII to the degree that induced behavioral changes. This emphasizes the possible synergistic effect of SB on the neurological manifestations of H. nana and could, in part, explain the increased incidence of behavioral changes in children exposed to high doses of SB and unfortunately have H. nana infection.

The findings of capsule endoscopy in patients with common variable immunodeficiency syndrome.

BACKGROUND/AIMS: Common variable immunodeficiency syndrome (CVIS) is a primary immunodeficiency disorder characterized by reduced serum immunoglobulins and heterogeneous clinical features. Parasitic and bacterial infections are very common complications of the syndrome. Capsule endoscopy (CE) represents a new and highly innovative method of demonstrating the small intestinal diseases. We evaluated the practical usefulness and diagnostic yield of CE in three patients with CVIS. METHODOLOGY: Between January 2003 and September 2004 CE was performed in 31 patients for different indications including mostly obscure gastrointestinal bleeding. We particularly evaluated 3 patients with CVIS whose diagnosis was based on serum immunoglobulins levels, clinical features and intestinal biopsy. The three CVIS patients with a median age of 25.6 years (ranged 21-34 years) have been followed-up for a period of 6.3 years (range 3-9 years). After introduction of CE in our medical center, this technique was performed with a Given M2A video capsule system in three patients to explain chronic severe and refractory diarrhea and iron deficiency anemia. RESULTS: All three patients were able to complete the study. In one of the three patients, CE demonstrated unlimited sessile and sometimes pedunculated polyp-like lesions of 2 to 6mm in diameter starting from antrum of the stomach to terminal ileum without escaping fashion and a parasite, Hymenolepsis nana that was located in the ileum of the patient. Biopsy obtained by conventional endoscopy from small intestine and antrum demonstrated typical nodular lymphoid hyperplasia. In the second patient, the same capsule endoscopic and histological findings were found on the mucosa of the duodenum and jejunum but not ileum and the stomach. In the third patient in whom the follow-up period was 3 years, CE revealed no abnormality through the small intestine. CONCLUSIONS: Our data indicated that CE may be necessary for the patients with CVIS to evaluate not only the complications but also extension of the small intestinal involvement.

Helminth infection enhances disease in a murine TH2 model of colitis.

BACKGROUND & AIMS: There is convincing evidence from animal and human studies that infection with parasitic helminths can alleviate the histopathology and symptoms of colitis. Here the ability of the rat tapeworm Hymenolepis diminuta to affect the course of oxazolone-induced colitis (a TH2 model) was assessed. METHODS: Mice were infected with H diminuta and 8 days later they received oxazolone (3 mg in 50% EtOH, intrarectal). On autopsy (3 or 7 days postoxazolone), disease severity was assessed by macroscopic clinical scores, histologic damage scores, myeloperoxidase and eosinophil peroxidase activity, and cytokine synthesis. RESULTS: As gauged by all markers of gut function, infection with H diminuta caused a significant exacerbation of oxazolone-induced colitis. Indeed, while mice receiving oxazolone only began to recover approximately 3-4 days posttreatment, the cotreated group continued to deteriorate. Helminth infection, independent of oxazolone administration, enhanced IL-4, IL-5, IL-10, and IL-13 production from in vitro stimulated immune cells and evoked increases in colonic eosinophil peroxidase of cotreated mice. Finally, while knockout of natural killer (NK) and NK-T cells by administration of a neutralizing NK1.1 antibody reduced the inflammation in oxazolone and oxazolone + H diminuta-treated animals, mice in the latter group still displayed significant colitis. CONCLUSIONS: We have shown that H diminuta infection is beneficial in other models of colitis. The current data is presented as a caveat to the position that parasitic helminths in general can be considered as a therapy for heterogeneous inflammatory disorders without careful analysis of the immunologic basis of the condition.

Tapeworm identification in the fat sand rat (Psammomys obesus obesus).

The identification of a tapeworm (Rodentolepis nana, formerly named Hymenolepis nana) infection in a research breeding colony of sand rats (Psammomys obesus obesus) was complicated because of the unexpected long length (< 150 mm) of the worms. Other morphologic features that were consistent with this identification included the number (24), size (16 mm), and shape of the hooks on the rostellum. No evidence of intermediate hosts was found in the colony. Previous surveys of natural populations of sand rats had not identified this tapeworm. However, a detailed search of the literature revealed that variation in the size of R. nana had been reported, thus supporting the final identification of the tapeworm. R. nana is important and interesting because of its zoonotic potential and because it is the only tapeworm that is able to infect its definitive host without use of an intermediate host. This report is presented to help clarify the ambiguity found in the laboratory animal literature about the differences in the size of R. nana among rodent species used in research.