Helminth infections are widespread worldwide, and pose a serious threat to human health and animal husbandry development. Understanding of helminth-host interactions is critical to effective control and ultimate eradication of helminthiasis. Following host infections, helminth infections firstly initiate innate immune responses and then mediate adaptive immune responses. Type 1 immune responses are predominant at early stage of helminth infections, which mainly play anti-infective actions, and type 2 immune responses are predominant at late stage of infections, which are associated with helminth immune evasion and aggravation of tissue damages. This review summarizes the progress of researches on type 1/2 immune responses-associated signaling pathways mediated by helminth infections in hosts.
Animals ; Humans ; Helminthiasis ; Helminths ; Immunity, Innate ; Signal Transduction ; Host-Parasite Interactions

Traditional medications used for treating autoimmune diseases often come with a wide range of adverse effects. Current treatments focus mainly on symptom management, resulting in significant health issues and financial burdens for patients. Recently, clinical research has demonstrated the potential of helminths and their derivatives as effective therapies for autoimmune disorders. Helminths, being a near-natural immunomodulator, exhibit milder effects than broad-spectrum immunosuppressants and corticosteroids, thereby presenting a promising alternative for the treatment of autoimmune diseases. However, different helminths' therapeutic efficacy and mechanisms and their derivatives in treating autoimmune diseases may vary. Therefore, we aim to review recent clinical advancements in the use of helminths and their derivatives for treating inflammatory bowel disease, multiple sclerosis, and autism spectrum disorder, with a view to offering novel clinical treatment approaches.
Animals ; Humans ; Autism Spectrum Disorder ; Autoimmune Diseases/drug therapy* ; Helminths ; Inflammatory Bowel Diseases

Mebendazole (MBZ), a microtubule depolymerizing drug commonly used for the treatment of helminthic infections, has recently been noted as a repositioning candidate for angiogenesis inhibition and cancer therapy. However, the definite anti-angiogenic mechanism of MBZ remains unclear. In this study, we explored the inhibitory mechanism of MBZ in endothelial cells (ECs) and developed a novel strategy to improve its anti-angiogenic therapy. Treatment of ECs with MBZ led to inhibition of EC proliferation in a dose-dependent manner in several culture conditions in the presence of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) or FBS, without selectivity of growth factors, although MBZ is known to inhibit VEGF receptor 2 kinase. Furthermore, MBZ inhibited EC migration and tube formation induced by either VEGF or bFGF. However, unexpectedly, treatment of MBZ did not affect FAK and ERK1/2 phosphorylation induced by these factors. Treatment with MBZ induced shrinking of ECs and caused G2-M arrest and apoptosis with an increased Sub-G1 fraction. In addition, increased levels of nuclear fragmentation, p53 expression, and active form of caspase 3 were observed. The marked induction of autophagy by MBZ was also noted. Interestingly, inhibition of autophagy through knocking down of Beclin1 or ATG5/7, or treatment with autophagy inhibitors such as 3-methyladenine and chloroquine resulted in marked enhancement of anti-proliferative and pro-apoptotic effects of MBZ in ECs. Consequently, we suggest that MBZ induces autophagy in ECs and that protective autophagy can be a novel target for enhancing the anti-angiogenic efficacy of MBZ in cancer treatment.
Apoptosis ; Autophagy* ; Caspase 3 ; Chloroquine ; Endothelial Cells* ; Fibroblast Growth Factor 2 ; Helminths ; Intercellular Signaling Peptides and Proteins ; Mebendazole* ; Microtubules ; Phosphorylation ; Phosphotransferases ; Receptors, Vascular Endothelial Growth Factor ; Vascular Endothelial Growth Factor A

The roles of mast cells in allergic diseases and helminth infections are well known. However, the roles of mast cells in T. gondii infection is poorly understood. This study was focused on the production of pro-inflammatory cytokines (TNF-α, IL-4), chemokines (CXCL8, MCP-1) and nitric oxide (NO) by mast cells in response to soluble lysate of T. gondii tachyzoites. Production of CXCL8 (IL-8), MCP-1, TNF-α and IL-4 were measured by RT-PCR and ELISA. Western blot were used for detection of CXCR-1 and CXCR2. Our results showed that T. gondii lysates triggered mast cells to release CXCL8, MCP-1, TNF-α, IL-4 and to produce NO. This suggests that mast cells play an important role in inflammatory responses to T. gondii.
Blotting, Western ; Chemokines ; Cytokines ; Enzyme-Linked Immunosorbent Assay ; Helminths ; Humans ; Interleukin-4 ; Mast Cells ; Nitric Oxide ; Toxoplasma

There have been some reports on schistosomiasis of school children in Sudan’s Nile River basin area; however, information about the infection status of Schistosoma species and intestinal helminths among village residents of this area is very limited. Urine and stool samples were collected from the 1,138 residents of the Al Hidaib and Khour Ajwal villages of White Nile State, Sudan in 2014. The prevalence of overall schistosomiasis and intestinal helminthiasis was 36.3% and 7.7%, respectively. Egg positive rates were 35.6% for Schistosoma haematobium, 2.6% for S. mansoni, and 1.4% were mixed. The prevalence of schistosomiasis was significantly higher in men (45.6%) than in women (32.0%), in Khou Ajwal villagers (39.4%) than in Al Hidaib villagers (19.2%), and for age groups ≤15 years old (51.5%) than for age groups >15 years old (13.2%). The average number of eggs per 10 ml urine (EP10) of S. haematobium infections was 18.9, with 22.2 eggs in men vs 17.0 in women and 20.4 in Khou Ajwal villagers vs 8.1 in Al Hidaib villagers. In addition to S. mansoni eggs, 4 different species of intestinal helminths were found in the stool, including Hymenolepis nana (6.6%) and H. diminuta (1.0%). Collectively, urinary schistosomiasis is still prevalent among village residents in Sudan’s White Nile River basin and was especially high in men, children ≤15 years, and in the village without a clean water system. H. nana was the most frequently detected intestinal helminths in the 2 villages.
Child ; Eggs ; Female ; Helminthiasis ; Helminths ; Humans ; Hymenolepis nana ; Male ; Ovum ; Prevalence ; Rivers ; Schistosoma ; Schistosoma haematobium ; Schistosoma mansoni ; Schistosomiasis haematobia ; Schistosomiasis ; Sudan ; Water

Adult specimens of Echinochasmus caninus n. comb. (Verma, 1935) (Trematoda: Echinostomatidae) (syn. Episthmium caninum Yamaguti, 1958) were recovered from 11 riparian people who resided along the Mekong River in Khammouane Province, Lao PDR. In fecal examinations done by the Kato-Katz technique, the cases revealed eggs of Opisthorchis viverrini/minute intestinal flukes, hookworms, and in 2 cases echinostome eggs. To recover the adult helminths, praziquantel 30–40 mg/kg and pyrantel pamoate 10–15 mg/kg in a single dose were given and purged with magnesium salts. Various species of trematodes (including O. viverrini and Haplorchis spp.), cestodes, and nematodes were recovered from their diarrheic stools. Among the trematodes, small echinostome flukes (n=42; av. 3.8 specimens per case) of 0.7–1.2 mm in length are subjected in this study. They are morphologically characterized by having 24 collar spines interrupted dorsally and anterior extension of vitellaria from the cirrus sac or genital pore level to the posterior end of the body. Particularly based on this extensive distribution of vitellaria, the specific diagnosis was made as Echinochasmus caninus. The cases were co-infected with various other helminth parasites; thus, clinical manifestations specific for this echinostome infection were difficult to determine. The present paper describes for the first time human E. caninus infections in Lao PDR. Our cases marked the 4–14th human infections with this echinostome around the world following the 3 previous cases reported from Thailand.
Adult ; Ancylostomatoidea ; Animals ; Cestoda ; Comb and Wattles ; Diagnosis ; Eggs ; Helminths ; Humans ; Magnesium ; Opisthorchis ; Ovum ; Parasites ; Praziquantel ; Pyrantel Pamoate ; Rivers ; Salts ; Spine ; Thailand ; Trematoda

Coenurosis is an important zoonotic helminthic disease caused by the larval stage of the tapeworm Taenia multiceps. This parasite typically infects the brain of the intermediate hosts, including sheep, goat, cattle and even humans. We report a case of T. multiceps infection in a yak confirmed by clinical symptoms, morphological characteristics, and molecular and phylogenetic analyses. The coenurus was thin-walled, whitish, and spherical in shape with a diameter of 10 cm. The parasite species was identified as T. multiceps by PCR amplification and sequencing of the 18S rRNA, cox1 and nad1 genes. Three gene sequences all showed high homology (all above 97%) with the reference sequences from different hosts. Moreover, phylogenetic reconstructions with the 3 published Taenia gene sequences confirmed that the Qinghai yak isolate was closely related to T. multiceps. Although there are advanced diagnosis and treatment methods for coenurosis, early infection is difficult to diagnose. Importantly, the findings of yak infection case should not be ignored due to its zoonotic potential.
Animals ; Brain ; Cattle ; Cestoda ; China ; Diagnosis ; Goats ; Helminths ; Humans ; Parasites ; Polymerase Chain Reaction ; Sheep ; Taenia

This study aimed to determine the prevalence of intestinal helminth parasitic infections and associated risk factors for the human infection among the people of Samarkand, Uzbekistan. Infection status of helminths including Echinococcus granulosus was surveyed in domestic and wild animals from 4 sites in the Samarkand region, Uzbekistan during 2015–2018. Fecal samples of each animal were examined with the formalin-ether sedimentation technique and the recovery of intestinal helminths was performed with naked eyes and a stereomicroscope in total 1,761 animals (1,755 dogs, 1 golden jackal, and 5 Corsac foxes). Total 658 adult worms of E. granulosus were detected in 28 (1.6%) dogs and 1 (100%) golden jackal. More than 6 species of helminths, i.e., Taenia hydatigena, Dipylidium caninum, Diplopylidium nolleri, Mesocestoides lineatus, Toxocara canis, and Trichuris vulpis, were found from 18 (1.0%) dogs. Six (T. hydatigena, Toxascaris leonina, Alaria alata, Uncinaria stenocephala, D. caninum, and M. lineatus) and 2 (D. nolleri and M. lineatus) species of helminths were also detected from 5 Corsac foxes and 1 golden jackal, respectively. Taeniid eggs were found in 2 (20%) out of 10 soil samples. In the present study, it was confirmed that the prevalences of helminths including E. granulosus are not so high in domestic and wild animals. Nevertheless, the awareness on the zoonotic helminth infections should be continuously maintained in Uzbekistan for the prevention of human infection.
Adult ; Ancylostomatoidea ; Animals ; Animals, Wild ; Dogs ; Echinococcus granulosus ; Eggs ; Foxes ; Helminths ; Humans ; Jackals ; Mesocestoides ; Ovum ; Prevalence ; Risk Factors ; Soil ; Taenia ; Toxascaris ; Toxocara canis ; Trichuris ; Uzbekistan

Environmental variations induced by industrialization and climate change partially explain the increase in prevalence and severity of allergic disease. One possible mechanism is the increase in allergen production leading to more exposure and sensitization in susceptible individuals. House dust mites (HDMs) are important sources of allergens inducing asthma and rhinitis, and experimentally they have been demonstrated to be very sensitive to microenvironment modifications; therefore, global or regional changes in temperature, humidity, air pollution or other environmental conditions could modify natural HDM growth, survival and allergen production. There is evidence that sensitization to HDMs has increased in some regions of the world, especially in the subtropical and tropical areas; however, the relationship of this increase with environmental changes is not so clear as has reported for pollen allergens. In this review, we address this point and explore the effects of current and predicted environmental changes on HDM growth, survival and allergen production, which could lead to immunoglobulin E (IgE) sensitization and allergic disease prevalence. We also assess the role of adjuvants of IgE responses, such as air pollution and helminth infections, and discuss the genetic and epigenetic aspects that could influence the adaptive process of humans to drastic and relatively recent environmental changes we are experiencing.
Air Pollution ; Allergens ; Asthma ; Climate Change ; Dust ; Epigenomics ; Helminths ; Humans ; Humidity ; Hypersensitivity ; Immunoglobulin E ; Immunoglobulins ; Pollen ; Prevalence ; Pyroglyphidae ; Rhinitis

Cathepsin D (CatD, EC 3.4.23.5) is a member belonging to the subfamily of aspartic endopeptidases, which are classified into the MEROPS clan AA, family A1. Helminth parasites express a large set of different peptidases that play pivotal roles in parasite biology and pathophysiology. However, CatD is less well known than the other classes of peptidases in terms of biochemical properties and biological functions. In this study, we identified 2 novel CatDs (CsCatD1 and CsCatD2) of Clonorchis sinensis and partially characterized their properties. Both CsCatDs represent typical enzymes sharing amino acid residues and motifs that are tightly conserved in the CatD superfamily of proteins. Both CsCatDs showed similar patterns of expression in different developmental stages of C. sinensis, but CsCatD2 was also expressed in metacercariae. CsCatD2 was mainly expressed in the intestines and eggs of C. sinensis. Sera obtained from rats experimentally infected with C. sinensis reacted with recombinant CsCatD2 beginning 2 weeks after infection and the antibody titers were gradually increased by maturation of the parasite. Structural analysis of CsCatD2 revealed a bilobed enzyme structure consisting of 2 antiparallel β-sheet domains packed against each other forming a homodimeric structure. These results suggested a plausible biological role of CsCatD2 in the nutrition and reproduction of parasite and its potential utility as a serodiagnostic antigen in clonorchiasis.
Animals ; Aspartic Acid Endopeptidases ; Biology ; Cathepsin D ; Cathepsins ; Clonorchiasis ; Clonorchis sinensis ; Eggs ; Helminths ; Humans ; Intestines ; Metacercariae ; Ovum ; Parasites ; Peptide Hydrolases ; Rats ; Reproduction