Enteric tuft cells coordinate timely expulsion of the tapeworm Hymenolepis diminuta from the murine host by coordinating local but not systemic immunity.

Recognizing that enteric tuft cells can signal the presence of nematode parasites, we investigated whether tuft cells are required for the expulsion of the cestode, Hymenolepis diminuta, from the non-permissive mouse host, and in concomitant anti-helminthic responses. BALB/c and C57BL/6 mice infected with H. diminuta expelled the worms by 11 days post-infection (dpi) and displayed DCLK1+ (doublecortin-like kinase 1) tuft cell hyperplasia in the small intestine (not the colon) at 11 dpi. This tuft cell hyperplasia was dependent on IL-4Rα signalling and adaptive immunity, but not the microbiota. Expulsion of H. diminuta was slowed until at least 14 dpi, but not negated, in tuft cell-deficient Pou2f3-/- mice and was accompanied by delayed goblet cell hyperplasia and slowed small bowel transit. Worm antigen and mitogen evoked production of IL-4 and IL-10 by splenocytes from wild-type and Pou2f3-/- mice was not appreciably different, suggesting similar systemic immune reactivity to infection with H. diminuta. Wild-type and Pou2f3-/- mice infected with H. diminuta displayed partial protection against subsequent infection with the nematode Heligmosomoides bakeri. We speculate that, with respect to H. diminuta, enteric tuft cells are important for local immune events driving the rapidity of H. diminuta expulsion but are not critical in initiating or sustaining systemic Th2 responses that provide concomitant immunity against secondary infection with H. bakeri.

[Hymenolepis diminuta infection in an adult's lung: a case report].

Hymenolepis diminuta is a common parasite of rats and mice, but is very rare in humans with cases reported from various parts of the world. Here, we reported a case of Hymenolepis diminuta infection involving both the respiratory and digestive tracts in a 49-year-old male patient whose initial imaging and symptoms were strikingly similar to pneumonia. Since no disease-causing pathogens were found during routine examinations, we considered respiratory infection by specific pathogens before metagenomic next-generation sequencing of broncho-alveolar lavage fluid confirmed the diagnosis of Hymenolepis diminuta. After confirming the diagnosis, we retested the patient's stool repeatedly and found Hymenolepis diminuta eggs finally. To help doctors better understand this condition and avoid misdiagnosis, this article provided a summary of the clinical characteristics, diagnostic techniques, and therapeutic options for infection by Hymenolepis diminuta.

Human infections by Hymenolepis diminuta in Europe: a case report and literature review.

We performed a review of published and gray literature of human Hymenolepis diminuta cases across Europe up to July 2022. Of all detectable publications and records, we further analyzed only those that contained demographic, clinical or epidemiological data regarding the infected subjects. Additionally, one case of hymenolepiasis in a 16-mo-old boy living in the urban part of Belgrade was included in the analysis. Published studies were based in 13/50 European countries and identified 104 laboratory-confirmed cases in total. Almost one-half (49%) of all cases originated from Mediterranean countries. Among symptomatic children, the infection most often manifested with diarrhea, abdominal pain, allergic reaction and behavioral changes. The diagnosis was made by the detection and identification of H. diminuta eggs or parts of strobila in stool samples, although cases of misdiagnosis were also reported. The parasite clearance was established with praziquantel or niclosamide, while the administration of albendazole or mebendazole led to unfavorable results. Future multicentric prospective studies focused on infection screening and the gathering of detailed sociodemographic and clinical data could provide an updated insight into the true distribution and characteristics of H. diminuta infection across Europe.

Efficacy of Lactobacillus taiwanensis S29 and Lactiplantibacillus plantarum S27 against tapeworm infection in Swiss Albino rats.

Hymenolepis diminuta a zoonotic tapeworm infection in human remains an important cestode model for anthelmintic study as it display common clinical symptoms like other adult human tapeworms during heavy infestation. The use of Lactobacillus as a probiotic is an alternative to drugs which have increased in research and usage considerably during the last decade. The present study aims to determine the anthelmintic efficacy of two probiotics, L. taiwanensis strain S29 and L. plantarum strain S27 against H. diminuta in infected rat. Four groups of animals, each with six numbers were randomly chosen as the negative control (Group I), positive control (infected) (Group II) and the infected treated with two probiotics Group III and Group IV respectively. Another four groups (Group V-VIII) were selected and further subdivided into four sub-groups to investigate the development of larvae to adult during probiotics treatment. Worm burden, egg per gram were determined after treatment with these two probiotics. Furthermore, hematological assays and levels of biochemical markers were estimated, tissue damage was assayed through histological study and intestinal mitochondria detection was done. Worm sustainability reduced about 70-90% and EPG count decreased by 81-94% in probiotics treated groups. A significant level of unsuccessful establishment of larvae was observed in the developmental phase. Improvement in hematological parameter along with some biochemical parameters in the host were significantly observed after treatment with probiotics. The architecture damaged caused in the intestine and mitochondria density due to parasite infection improved significantly as that of control after probiotics treatment.

Human infections by the rat tapeworm Hymenolepis diminuta in China.

The rat tapeworm Hymenolepis diminuta is a parasite that usually uses rats as a definitive host. It also infects humans and non-human primates. Human infections have been reported in 80 countries worldwide, including China. Nevertheless, nearly all the literature on human infections in China by the rat tapeworm is in Chinese journals, which are very difficult to access by readers outside China. The main aim of the current manuscript was to systematically review human infections by the rat tapeworm in China for readers inside and outside the country. Chinese characters for H. diminuta were used to search several databases, including Google Scholar. In total, 511 infections were reported in 24 Chinese provinces/autonomous regions, which surpassed 320 in Costa Rica as the country with the highest number of infections. Furthermore, three nationwide surveys on parasitic infections in the past 3 decades revealed detailed prevalence of this parasite along with that of roundworm, whipworm, hookworm and pinworm in Chinese populations. These data contribute to better understanding of this greatly neglected zoonosis in the world's most populated country.

Gallic acid and Catechin induce morphological alterations on the zoonotic parasite Hymenolepis diminuta.

Tapeworm infections cause insidious and irreversible effects in the infected individuals and some of them have already shown resistance to available drugs. A search for alternative treatment is urgently required. Phenolic compounds are amongst the most researched natural substances for their medicinal use. The present study aims to determine anthelmintic efficacy of two polyphenols Gallic acid and Catechin against the zoonotic rat tapeworm Hymenolepis diminuta. Both compounds are potent anti-oxidants and play major roles in combating pathogens, while their anthelmintic property according to our knowledge is yet to be explored. The parasite model H. diminuta was procured from intestine of infected rats raised in our laboratory. Two sets of parasites were treated in vitro with 5, 10, 20 and 40 mg/ml concentrations of each Gallic Acid and Catechin separately, another set of parasites were treated with standard dose of Praziquantel in RPMI 1640, while still another set of worms were kept in RPMI 1640 at 37 ± 10C with 1% Dimethyl sulfoxide as control. Motility and structural alterations were the parameters assessed for anthelmintic efficacy of the compounds. After paralysis the worms were processed for morphological, histological, and ultrastructural study and observed under light and electron microscope. Dose-dependent efficacy was observed in both compounds. Shrinkage of suckers, deformed proglottids and architectural alteration of the tegument were observed throughout the body of treated parasites compared to control. Although in terms of time taken for paralysis and mortality Gallic acid was more effective than Catechin, the degree of morphological aberrations caused were almost similar, except histological alteration was more in Catechin treated worms than in Gallic acid. Nevertheless, both Gallic acid and Catechin are suggested to possess anthelmintic efficacy besides other health benefits but extended studies are required to compare their efficacy.

Hymenolepiasis Caused by Hymenolepis nana in Humans and Natural Infection in Rodents in a Marginal Urban Sector of Guayaquil, Ecuador.

BACKGROUND Hymenolepiasis is a globally prevalent zoonosis of the monoxenic cycle. Humans acquire the disease through fecal-oral transmission by ingesting food or water with infective eggs from infected rodents. This report presents 3 cases of hymenolepiasis in children, due to zoonotic transmission from rodents and presumably associated with the consumption of powdered milk contaminated with infective eggs of Hymenolepis nana, and shows that awareness and early diagnosis contributed to timely treatment of the disease. CASE REPORT Three children, aged 9, 12, and 13 years, living in a marginal urban area of Guayaquil, Guayas province, Ecuador, presented symptoms of diarrhea, low body weight, abdominal discomfort, anorexia, paleness, and anal itching. Subsequently, their fecal samples were analyzed by direct coproparasitic methods, flotation and sedimentation with centrifugation using saline solution; the presence of H. nana eggs was determined. Blood biometry was performed. Further, 10 rodents were captured and necropsied to obtain intestinal contents. The powdered milk consumed by the children was analyzed, the same powder that contained rodent feces. Subsequently, these were studied with the above-mentioned coproparasitic methods. H. nana eggs were identified in the 6 trapped rodents, the powdered milk, and the feces of rodents found in the milk powder. CONCLUSIONS Hymenolepiasis can affect populations of endemic areas. In this case, the disease was identified in 3 children, who were diagnosed with eosinophilia and anemia. Additionally, the presence of H. nana eggs in captured rodents and in powdered milk was determined, indicating that the community was exposed to this zoonotic disease.

Hymenolepis diminuta, phylogenetic analyses of nuclear rRNA + ITS and mitochondrial cox1 and its infections in non-human primates.

Hymenolepis diminuta is a tapeworm commonly found worldwide in small rodents such as rats with occasional reports in other definitive hosts such as primates including chimpanzees and humans. It has not been reported in African green monkey (AGM, Chlorocebus sabaeus), and the parasite's molecular phenotype and phylogeny remain primitively sketchy. The aims of the current study were to determine if H. diminuta infected AGMs, to molecularly characterize H. diminuta and to review its infection in non-human primates. Feces of AGMs were examined visually for adult helminths and microscopically for eggs using centrifugation flotation. Total DNA extracted from eggs was amplified by PCR followed by DNA sequencing of targeted sequences of nuclear rRNA + internal transcribed spacers (ITS) and mitochondrial cox1. Phylogenetic analyses were performed. The DNA sequences of both nuclear rRNA + ITS and mitochondrial cox1 showed more than 98% and 99% identity to the known sequences respectively. Hymenolepis diminuta has been reported in various non-human primates with the highest prevalence of 38.5% in the white-headed capuchin monkey. The study presented here confirms that this tapeworm is capable of infecting various species of non-human primates with the first report of infections in AGM. Phylogenetic analyses of rRNA + ITS and mitochondrial cox1 demonstrated three separated clades I, II and III with the newly described AGM1 isolate belonging to the clade I. Whether these differences are at species level remains to be confirmed.

Hymenolepis diminuta Infection Affects Apoptosis in the Small and Large Intestine.

The rat tapeworm Hymenolepis diminuta has been shown to cause alterations in gastrointestinal tissues. Since hymenolepiasis induces a number of reactions in the host, it is reasonable to assume that it may also be involved in the mechanisms of apoptosis in the intestines. Individual research tasks included an examination of the effect of H. diminuta infection on; (i) the cellular localization of the expression of pro-apoptotic protein Bax and anti-apoptotic protein Bcl-2, as well as caspase-3 and caspase-9, and (ii) the effects of the infection on the expression of Bcl-2, Bax, Cas-3 and Cas-9, at the mRNA and protein levels. Molecular tests (including mRNA (qRT PCR) and the protein (Western blot) expression of Bax, Bcl-2, and caspases-3, -9) and immunohistochemical tests were performed during the experiment. They showed that H. diminuta infection activates the intrinsic apoptosis pathway in the small and large intestine of the host. H. diminuta infection triggered the apoptosis via the activation of the caspase cascade, including Cas-3 and Cas-9. Hymenolepiasis enhanced apoptosis in the small and large intestine of the host by increasing the expression of the pro-apoptotic gene and protein Bax and by decreasing the expression of the anti-apoptotic gene and protein Bcl-2.

Infection with intestinal helminth (Hymenolepis diminuta) impacts exploratory behavior and cognitive processes in rats by changing the central level of neurotransmitters.

Parasites may significantly affect the functioning of the host organism including immune response and gut-brain-axis ultimately leading to alteration of the host behavior. The impact of intestinal worms on the host central nervous system (CNS) remains unexplored. The aim of this study was to evaluate the effect of intestinal infection by the tapeworm Hymenolepis diminuta on behavior and functions of the CNS in rats. The 3 months old animals were infected, and the effects on anxiety, exploration, sensorimotor skills and learning processes were assessed at 18 months in Open Field (OF), Novel Object Recognition (NOR) and the Water Maze (WM) tests. After completing the behavioral studies, both infected and non-infected rats were sacrificed, and the collected tissues were subjected to biochemical analysis. The levels of neurotransmitters, their metabolites and amino acids in selected structures of the CNS were determined by HPLC. In addition, the gene expression profile of the pro- and anti-inflammatory cytokines (TNF-α, IL-1ß, IL-6 and IL-10) was evaluated by Real-Time PCR to determine the immune response within the CNS to the tapeworm infection. The parasites caused significant changes in exploratory behavior, most notably, a reduction of velocity and total distance moved in the OF test; the infected rats exhibited decreased frequency in the central zone, which may indicate a higher level of anxiety. Additionally, parasite infestation improved spatial memory, assessed in the WM test, and recognition of new objects. These changes are related to the identified reduction in noradrenaline level in the CNS structures and less pronounced changes in striatal serotonergic neurotransmission. H. diminuta infestation was also found to cause a significant reduction of hippocampal expression of IL-6. Our results provide new data for further research on brain function during parasitic infections especially in relation to helminths and diseases in which noradrenergic system may play an important role.

Occurrence of Hymenolepis diminuta: a potential helminth of zoonotic importance in murid rodents / Ocorrência de Hymenolepis diminuta: um helminto potencial de importância zoonótica em roedores murídeos

The study reveals the prevalence of a potential rodent-borne zoonotic helminth species, Hymenolepis diminuta in commensal rodents caught from irrigated and rain-fed areas of Swat, Pakistan. Three hundred and fifty rodents (269 rats and 81 mice) trapped during vegetative, flowering/fruiting and mature/harvesting stages of crops were studied from 2011-2013. Hymenolepisdiminuta eggs were identified on the basis of their shape, size, colour and markings on the surface of the egg shell and three pairs of embryonic hook-lets. Overall prevalence of H. diminuta was 3.14% (n=11/350). The highest prevalence 3.49% (n=5/143) of H. diminuta was noted at harvesting stages of the crops whereas the lowest 2.59% (n=2/77) during vegetative stage. Infection was higher in males 3.25% (n=7/215) than females 2.96% (n=4/135). Adult rodents were highly infected while no sub-adult was found infected. Infection was higher in mice 3.70% (3/81) than rats 2.69% (8/269) while no significance (p=1.0000:0.1250 to 32.00 CI). Rats and mice appears to show the most suitable reservoirs by hosting H. diminuta a zoonotic helminth. The presence of these rodents in all possible habitats can act as a main channel of transferring parasites through various habitats and can pose a hazard to humans in the area.

O estudo revela a prevalência de uma espécie potencial de helmintos zoonóticos transmitidos por roedores, Hymenolepis diminuta, em roedores comensais capturados em áreas irrigadas e alimentadas pela chuva de Swat, Paquistão. Trezentos e cinquenta roedores (269 ratos e 81 camundongos) presos durante os estágios vegetativo, floração/frutificação e maturidade/colheita das safras foram estudados de 2011-2013. Ovos de Hymenolepisdiminuta foram identificados com base em sua forma, tamanho, cor e marcações na superfície da casca do ovo e três pares de anzóis embrionários. A prevalência geral de H. diminuta foi de 3,14% (n = 11/350). A maior prevalência 3,49% (n = 5/143) de H. diminuta foi observada na fase de colheita das lavouras, enquanto a menor 2,59% (n = 2/77) durante a fase vegetativa. A infecção foi maior nos homens 3,25% (n = 7/215) do que nas mulheres 2,96% (n = 4/135). Roedores adultos foram altamente infectados, enquanto nenhum subadulto foi encontrado infectado. A infecção foi maior em camundongos 3,70% (3/81) do que em ratos 2,69% (8/269), embora sem significância (p = 1,0000: 0,1250 a 32,00 CI). Ratos e camundongos parecem mostrar os reservatórios mais adequados hospedando H. diminuta um helmintos zoonótico. A presença desses roedores em todos os habitats possíveis pode atuar como um canal principal de transferência de parasitas através de vários habitats e pode representar um perigo para os humanos na área.

Cooperation between host immunity and the gut bacteria is essential for helminth-evoked suppression of colitis.

BACKGROUND: Studies on the inhibition of inflammation by infection with helminth parasites have, until recently, overlooked a key determinant of health: the gut microbiota. Infection with helminths evokes changes in the composition of their host's microbiota: one outcome of which is an altered metabolome (e.g., levels of short-chain fatty acids (SCFAs)) in the gut lumen. The functional implications of helminth-evoked changes in the enteric microbiome (composition and metabolites) are poorly understood and are explored with respect to controlling enteric inflammation. METHODS: Antibiotic-treated wild-type, germ-free (GF) and free fatty-acid receptor-2 (ffar2) deficient mice were infected with the tapeworm Hymenolepis diminuta, then challenged with DNBS-colitis and disease severity and gut expression of the il-10 receptor-α and SCFA receptors/transporters assessed 3 days later. Gut bacteria composition was assessed by 16 s rRNA sequencing and SCFAs were measured. Other studies assessed the ability of feces or a bacteria-free fecal filtrate from H. diminuta-infected mice to inhibit colitis. RESULTS: Protection against disease by infection with H. diminuta was abrogated by antibiotic treatment and was not observed in GF-mice. Bacterial community profiling revealed an increase in variants belonging to the families Lachnospiraceae and Clostridium cluster XIVa in mice 8 days post-infection with H. diminuta, and the transfer of feces from these mice suppressed DNBS-colitis in GF-mice. Mice treated with a bacteria-free filtrate of feces from H. diminuta-infected mice were protected from DNBS-colitis. Metabolomic analysis revealed increased acetate and butyrate (both or which can reduce colitis) in feces from H. diminuta-infected mice, but not from antibiotic-treated H. diminuta-infected mice. H. diminuta-induced protection against DNBS-colitis was not observed in ffar2-/- mice. Immunologically, anti-il-10 antibodies inhibited the anti-colitic effect of H. diminuta-infection. Analyses of epithelial cell lines, colonoids, and colon segments uncovered reciprocity between butyrate and il-10 in the induction of the il-10-receptor and butyrate transporters. CONCLUSION: Having defined a feed-forward signaling loop between il-10 and butyrate following infection with H. diminuta, this study identifies the gut microbiome as a critical component of the anti-colitic effect of this helminth therapy. We suggest that any intention-to-treat with helminth therapy should be based on the characterization of the patient's immunological and microbiological response to the helminth.

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.

Worm expulsion is independent of alterations in composition of the colonic bacteria that occur during experimental Hymenolepis diminuta-infection in mice.

The tapeworm Hymenolepis diminuta fails to establish in mice. Given the potential for helminth-bacteria interaction in the gut and the influence that commensal bacteria exert on host immunity, we tested if worm expulsion was related to alterations in the gut microbiota. Specific pathogen-free (SPF) mice, treated with broad-spectrum antibiotics, or germ-free wild-type mice were infected with H. diminuta, gut bacterial composition assessed by 16S rRNA gene sequencing, and worm counts, blood eosinophilia, goblet cells, splenic IL-4, -5 and -10, and colonic cytokines/chemokines mRNA were assessed. Effects of a PBS-soluble extract of adult H. diminuta on bacterial growth in vitro was tested. H. diminuta-infected mice displayed increased α and ß diversity in colonic mucosa-associated and fecal bacterial communities, characterized by increased Lachnospiraceae and clostridium cluster XIVa. In vitro analysis revealed that the worm extract promoted the growth of anaerobic bacteria on M2GSC agar. H. diminuta-infection was accompanied by increased Th2 immune responses, and colon from infected mice had increased levels of IL-10, IL-25, Muc2, trefoil factor 3, and ß2-defensin mRNA. SPF-mice treated with antibiotics, or germ-free mice, expelled H. diminuta with kinetics similar to control SPF mice. In both settings, measurements of Th2-immune responses were not significantly different across the groups. Thus, while infection with H. diminuta results in subtle but distinct changes to the colonic microbiota, we have no evidence to support an essential role for gut bacteria in the expulsion of the worm from the mouse host.

Comparison of the effects of multiple variables on the levels of infection of the rat tapeworm, Hymenolepis diminuta, in its intermediate host, the confused flour beetle Tribolium confusum.

The interaction of the rat tapeworm, Hymenolepis diminuta, with its intermediate beetle host, Tribolium confusum, is a well-studied model system. However, there is so much variation in the methods and designs of the studies that it is difficult to draw comparisons. This study simultaneously compared several aspects of the infection protocol including beetle age, sex, density and mating status; parasite egg condition, infection environment humidity and the times for the three steps of infection: starvation, feeding and post-feeding development. Although statistically limited by low prevalence and intensity levels, we were able to detect the relative effects of the variables. The effects of these variables on prevalence (percent infection) and intensity (mean number of cysticercoids) do not necessarily correlate with each other. Egg condition, reduced starvation times, higher beetle density and longer development times reduced prevalence. However, differences in intensity were only detected with older beetles. When coupled with survivorship data, our study found that our current infection protocol is optimal for infection success. However, the results suggest extending the study to other intermediate hosts and the inclusion of additional variables.

Suppression of systemic lupus erythematosus in NZBWF1 mice infected with Hymenolepis microstoma.

Intestinal helminths induce immune suppressive responses thought to regulate inflammatory diseases including allergies and autoimmune diseases. This study was designed to evaluate whether helminthic infections suppress the natural development of systemic lupus erythematosus (SLE) in NZBWF1 mice. Infection of NZBWF1 SLE-prone mice with two nematodes failed to establish long-lasting settlement. However, the Hymenolepis microstoma (Hm) rodent tapeworm successfully established long-term parasitization of NZBWF1 mice and was used to evaluate the suppressive effects of helminth infection. Ten-month-old NZBWF1 mice developed symptoms including autoantibody generation, proteinuria, glomerular histopathology, and splenomegaly, but mice infected with Hm at 2 months of age did not show any clinical signs. Furthermore, infection with Hm reduced lymphocyte activation and increased regulatory T cells in the spleen and mesenteric lymph nodes. These results indicate that infection with Hm protects NZBWF1 mice from naturally developing SLE and suggest that pathological immunity is attenuated, presumably because of the induction of regulatory T cells.