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The Korean Journal of Parasitology Jun 2021The use of albendazole and mebendazole, i.e., benzimidazole broad-spectrum anthelmintics, in treatment of parasitic infections, as well as cancers, is briefly reviewed.... (Review)
Review
The use of albendazole and mebendazole, i.e., benzimidazole broad-spectrum anthelmintics, in treatment of parasitic infections, as well as cancers, is briefly reviewed. These drugs are known to block the microtubule systems of parasites and mammalian cells leading to inhibition of glucose uptake and transport and finally cell death. Eventually they exhibit ovicidal, larvicidal, and vermicidal effects on parasites, and tumoricidal effects on hosts. Albendazole and mebendazole are most frequently prescribed for treatment of intestinal nematode infections (ascariasis, hookworm infections, trichuriasis, strongyloidiasis, and enterobiasis) and can also be used for intestinal tapeworm infections (taeniases and hymenolepiasis). However, these drugs also exhibit considerable therapeutic effects against tissue nematode/cestode infections (visceral, ocular, neural, and cutaneous larva migrans, anisakiasis, trichinosis, hepatic and intestinal capillariasis, angiostrongyliasis, gnathostomiasis, gongylonemiasis, thelaziasis, dracunculiasis, cerebral and subcutaneous cysticercosis, and echinococcosis). Albendazole is also used for treatment of filarial infections (lymphatic filariasis, onchocerciasis, loiasis, mansonellosis, and dirofilariasis) alone or in combination with other drugs, such as ivermectin or diethylcarbamazine. Albendazole was tried even for treatment of trematode (fascioliasis, clonorchiasis, opisthorchiasis, and intestinal fluke infections) and protozoan infections (giardiasis, vaginal trichomoniasis, cryptosporidiosis, and microsporidiosis). These drugs are generally safe with few side effects; however, when they are used for prolonged time (>14-28 days) or even only 1 time, liver toxicity and other side reactions may occur. In hookworms, Trichuris trichiura, possibly Ascaris lumbricoides, Wuchereria bancrofti, and Giardia sp., there are emerging issues of drug resistance. It is of particular note that albendazole and mebendazole have been repositioned as promising anti-cancer drugs. These drugs have been shown to be active in vitro and in vivo (animals) against liver, lung, ovary, prostate, colorectal, breast, head and neck cancers, and melanoma. Two clinical reports for albendazole and 2 case reports for mebendazole have revealed promising effects of these drugs in human patients having variable types of cancers. However, because of the toxicity of albendazole, for example, neutropenia due to myelosuppression, if high doses are used for a prolonged time, mebendazole is currently more popularly used than albendazole in anti-cancer clinical trials.
Topics: Albendazole; Animals; Anthelmintics; Antineoplastic Agents; Ascariasis; Female; Humans; Male; Mebendazole; Parasites; Trichuriasis
PubMed: 34218593
DOI: 10.3347/kjp.2021.59.3.189 -
Clinical Microbiology Reviews Dec 2021Microsporidia are obligate intracellular pathogens identified ∼150 years ago as the cause of pébrine, an economically important infection in silkworms. There are...
Microsporidia are obligate intracellular pathogens identified ∼150 years ago as the cause of pébrine, an economically important infection in silkworms. There are about 220 genera and 1,700 species of microsporidia, which are classified based on their ultrastructural features, developmental cycle, host-parasite relationship, and molecular analysis. Phylogenetic analysis suggests that microsporidia are related to the fungi, being grouped with the Cryptomycota as a basal branch or sister group to the fungi. Microsporidia can be transmitted by food and water and are likely zoonotic, as they parasitize a wide range of invertebrate and vertebrate hosts. Infection in humans occurs in both immunocompetent and immunodeficient hosts, e.g., in patients with organ transplantation, patients with advanced human immunodeficiency virus (HIV) infection, and patients receiving immune modulatory therapy such as anti-tumor necrosis factor alpha antibody. Clusters of infections due to latent infection in transplanted organs have also been demonstrated. Gastrointestinal infection is the most common manifestation; however, microsporidia can infect virtually any organ system, and infection has resulted in keratitis, myositis, cholecystitis, sinusitis, and encephalitis. Both albendazole and fumagillin have efficacy for the treatment of various species of microsporidia; however, albendazole has limited efficacy for the treatment of Enterocytozoon bieneusi. In addition, immune restoration can lead to resolution of infection. While the prevalence rate of microsporidiosis in patients with AIDS has fallen in the United States, due to the widespread use of combination antiretroviral therapy (cART), infection continues to occur throughout the world and is still seen in the United States in the setting of cART if a low CD4 count persists.
Topics: Gastrointestinal Diseases; Humans; Microsporidia; Microsporidiosis; Phylogeny; Prevalence
PubMed: 34190570
DOI: 10.1128/CMR.00010-20 -
Journal of Clinical Microbiology Nov 2014Microsporidia are highly specialized obligate intracellular organisms that are closely related to fungi. Although traditionally associated with diarrheal illness in... (Review)
Review
Microsporidia are highly specialized obligate intracellular organisms that are closely related to fungi. Although traditionally associated with diarrheal illness in patients with AIDS, extraintestinal infections involving various organs have been reported with increasing frequency in the past decade, particularly in immunocompromised hosts. Diagnosis is usually accomplished by light microscopic identification of spores in body fluids and tissues, using a variety of stains. Transmission electron microscopy, immunofluorescence assays, or molecular methods are necessary for identification to the genus and species level. Early diagnosis is essential for preventing the significant associated morbidity and mortality of extraintestinal microsporidiosis.
Topics: Humans; Immunocompromised Host; Microbiological Techniques; Microsporidia; Microsporidiosis
PubMed: 24829239
DOI: 10.1128/JCM.00971-14 -
Current Opinion in Microbiology Aug 2015Microsporidia comprise one of the largest groups of obligate intracellular pathogens and can infect virtually all animals, but host response to these fungal-related... (Review)
Review
Microsporidia comprise one of the largest groups of obligate intracellular pathogens and can infect virtually all animals, but host response to these fungal-related microbes has been poorly understood. Several new studies of the host transcriptional response to microsporidia infection have found infection-induced regulation of genes involved in innate immunity, ubiquitylation, metabolism, and hormonal signaling. In addition, microsporidia have recently been shown to exploit host recycling endocytosis for exit from intestinal cells, and to interact with host degradation pathways. Microsporidia infection has also been shown to profoundly affect behavior in insect hosts. Altogether, these and other recent findings are providing much-needed insight into the underlying mechanisms of microsporidia interaction with host animals.
Topics: Animals; Disease Models, Animal; Host-Pathogen Interactions; Humans; Immunity, Innate; Insecta; Microsporidia; Microsporidiosis
PubMed: 25847674
DOI: 10.1016/j.mib.2015.03.006 -
Frontiers in Microbiology 2020Microsporidia are found worldwide and both vertebrates and invertebrates can serve as hosts for these organisms. While microsporidiosis in humans can occur in both... (Review)
Review
Microsporidia are found worldwide and both vertebrates and invertebrates can serve as hosts for these organisms. While microsporidiosis in humans can occur in both immune competent and immune compromised hosts, it has most often been seen in the immune suppressed population, e.g., patients with advanced HIV infection, patients who have had organ transplantation, those undergoing chemotherapy, or patients using other immune suppressive agents. Infection can be associated with either focal infection in a specific organ (e.g., keratoconjunctivitis, cerebritis, or hepatitis) or with disseminated disease. The most common presentation of microsporidiosis being gastrointestinal infection with chronic diarrhea and wasting syndrome. In the setting of advanced HIV infection or other cases of profound immune deficiency microsporidiosis can be extremely debilitating and carries a significant mortality risk. Microsporidia are transmitted as spores which invade host cells by a specialized invasion apparatus the polar tube (PT). This review summarizes recent studies that have provided information on the composition of the spore wall and PT, as well as insights into the mechanism of invasion and interaction of the PT and spore wall with host cells during infection.
PubMed: 32132983
DOI: 10.3389/fmicb.2020.00172 -
Revista Chilena de Infectologia :... 2018
Topics: Microsporidia; Microsporidiosis
PubMed: 29652974
DOI: 10.4067/s0716-10182018000100073 -
Frontiers in Microbiology 2022Microsporidia are obligate intracellular, spore-forming parasitic fungi which are grouped with the Cryptomycota. They are both opportunistic pathogens in humans and... (Review)
Review
Microsporidia are obligate intracellular, spore-forming parasitic fungi which are grouped with the Cryptomycota. They are both opportunistic pathogens in humans and emerging veterinary pathogens. In humans, they cause chronic diarrhea in immune-compromised patients and infection is associated with increased mortality. Besides their role in pébrine in sericulture, which was described in 1865, the prevalence and severity of microsporidiosis in beekeeping and aquaculture has increased markedly in recent decades. Therapy for these pathogens in medicine, veterinary, and agriculture has become a recent focus of attention. Currently, there are only a few commercially available antimicrosporidial drugs. New therapeutic agents are needed for these infections and this is an active area of investigation. In this article we provide a comprehensive summary of the current as well as several promising new agents for the treatment of microsporidiosis including: albendazole, fumagillin, nikkomycin, orlistat, synthetic polyamines, and quinolones. Therapeutic targets which could be utilized for the design of new drugs are also discussed including: tubulin, type 2 methionine aminopeptidase, polyamines, chitin synthases, topoisomerase IV, triosephosphate isomerase, and lipase. We also summarize reports on the utility of complementary and alternative medicine strategies including herbal extracts, propolis, and probiotics. This review should help facilitate drug development for combating microsporidiosis.
PubMed: 35356517
DOI: 10.3389/fmicb.2022.835390 -
Trends in Parasitology Apr 2016Intensification of food production has the potential to drive increased disease prevalence in food plants and animals. Microsporidia are diversely distributed,... (Review)
Review
Intensification of food production has the potential to drive increased disease prevalence in food plants and animals. Microsporidia are diversely distributed, opportunistic, and density-dependent parasites infecting hosts from almost all known animal taxa. They are frequent in highly managed aquatic and terrestrial hosts, many of which are vulnerable to epizootics, and all of which are crucial for the stability of the animal-human food chain. Mass rearing and changes in global climate may exacerbate disease and more efficient transmission of parasites in stressed or immune-deficient hosts. Further, human microsporidiosis appears to be adventitious and primarily associated with an increasing community of immune-deficient individuals. Taken together, strong evidence exists for an increasing prevalence of microsporidiosis in animals and humans, and for sharing of pathogens across hosts and biomes.
Topics: Animals; Communicable Diseases, Emerging; Food Chain; Food Parasitology; Humans; Microsporidia; Microsporidiosis
PubMed: 26796229
DOI: 10.1016/j.pt.2015.12.004 -
Developmental and Comparative Immunology Nov 2016Fish intestinal parasites cause direct mortalities and also morbidity, poor growth, higher susceptibility to opportunistic pathogens and lower resistance to stress. This... (Review)
Review
Fish intestinal parasites cause direct mortalities and also morbidity, poor growth, higher susceptibility to opportunistic pathogens and lower resistance to stress. This review is focused on microscopic parasites (Protozoa and Metazoa) that invade the gastrointestinal tract of fish. Intracellular parasites (mainly Microsporidia and Apicomplexa) evoke almost no host immune reaction while they are concealed in the cytoplasmic and nuclear compartments, and can even use fish cells (macrophages) as Trojan horses to spread in the host. Inflammatory reaction only appears when the parasite bursts infected cells. Immunity against extracellular parasites is depicted for the myxozoans Ceratonova shasta and Enteromyxum spp. The cellular and humoral innate responses and the production of antibodies are crucial for resolving some of these myxozoonoses, but an excessive inflammatory reaction (concerted by cytokines) can become a fatal pathophysiological consequence. The local immune response plays a key role, with numerous genes more strongly regulated in the intestine than at lymphohaematopoietic organs.
Topics: Animals; Apicomplexa; Fishes; Gastrointestinal Tract; Immune Evasion; Immunity, Innate; Inflammation; Microsporidia; Microsporidiosis; Myxozoa; Parasitic Diseases, Animal; Protozoan Infections
PubMed: 26828391
DOI: 10.1016/j.dci.2016.01.014 -
Expert Opinion on Therapeutic Targets Nov 2018Microsporidia have been increasingly reported to infect humans. The most common presentation of microsporidiosis is chronic diarrhea, a significant mortality risk in... (Review)
Review
Microsporidia have been increasingly reported to infect humans. The most common presentation of microsporidiosis is chronic diarrhea, a significant mortality risk in immune-compromised patients. Albendazole, which inhibits tubulin, and fumagillin, which inhibits methionine aminopeptidase type 2 (MetAP2), are the two main therapeutic agents used for treatment of microsporidiosis. In addition, to their role as emerging pathogens in humans, microsporidia are important pathogens in insects, aquaculture, and veterinary medicine. New therapeutic targets and therapies have become a recent focus of attention for medicine, veterinary, and agricultural use. Areas covered: Herein, we discuss the detection and symptoms of microsporidiosis in humans and the therapeutic targets that have been utilized for the design of new drugs for the treatment of this infection, including triosephosphate isomerase, tubulin, MetAP2, topoisomerase IV, chitin synthases, and polyamines. Expert opinion: Enterocytozoon bieneusi is the most common microsporidia in human infection. Fumagillin has a broader anti-microsporidian activity than albendazole and is active against both Ent. bieneusi and Encephaliozoonidae. Microsporidia lack methionine aminopeptidase type 1 and are, therefore, dependent on MetAP2, while mammalian cells have both enzymes. Thus, MetAP2 is an essential enzyme in microsporidia and new inhibitors of this pathway have significant promise as therapeutic agents.
Topics: Albendazole; Animals; Antifungal Agents; Cyclohexanes; Drug Design; Fatty Acids, Unsaturated; Humans; Microsporidia; Microsporidiosis; Molecular Targeted Therapy; Sesquiterpenes
PubMed: 30336698
DOI: 10.1080/14728222.2018.1538360