Authors: Bing Han, Guoqing Pan, Louis M Weiss...

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

Review

Authors: Poornima Ramanan, Bobbi S Pritt

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

Review

Authors: Suzannah C Szumowski, Emily R Troemel

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

Review

Authors: Süleyman Yazar, Ozgür Koru, Berna Hamamcı...

All microsporidia are obligate parasites and have no active stages outside their host cells. Microsporidia lack some typical eukaryotic characteristics. There are now over 1200 species identified in 144 genera. The most familiar stage of microsporidia is the small, highly resistant spore, the size of which differs according to the species and is often 1-10 μm. The general life cycle pattern of the microsporidia can be divided into three phases: the infective or environmental phase, the proliferative phase, and the sporogony or spore-forming phase. There are several methods for diagnosing microsporidia: light microscopic, transmission electron microscopy (TEM), immunofluorescence assays (IFA) and molecular methods. The clinical course of microsporidiosis depends on the immune status of the host and site of infection. Microsporidia can cause infections such as diarrhoea, keratitis, myositis, bronchitis and brochiolitis. Human microsporidiosis represents an important and rapidly emerging opportunistic disease, occurring mainly, but not exclusively, in severely immunocompromised patients with AIDS. The treatment of microsporidiosis is generally achieved with medications and supportive care. Depending on the site of infection and the microsporidia species involved, different medications are utilized. The most commonly used medications for microsporidiosis include albendazole and fumagillin.

Topics: Animals; Antifungal Agents; Humans; Immunocompromised Host; Life Cycle Stages; Microsporidia; Microsporidiosis; Opportunistic Infections; Spores, Fungal

PubMed: 23955911
DOI: 10.5152/tpd.2013.28

Review

Authors: Elizabeth S Didier, Louis M Weiss

PURPOSE OF REVIEW

Microsporidiosis is an emerging and opportunistic infection associated with a wide range of clinical syndromes in humans. This review highlights the research on microsporidiosis in humans during the previous 2 years.

RECENT FINDINGS

The reduced and compact microsporidian genome has generated much interest for better understanding the evolution of these parasites, and comparative molecular phylogenetic studies continue to support a relationship between the microsporidia and fungi. Through increased awareness and improved diagnostics, microsporidiosis has been identified in a broader range of human populations that, in addition to persons with HIV infection, includes travelers, children, organ transplant recipients, and the elderly.

SUMMARY

Effective commercial therapies for Enterocytozoon bieneusi, the most common microsporidian species identified in humans, are still lacking, making the need to develop tissue culture and small animal models increasingly urgent. Environmental transport modeling and disinfection strategies are being addressed for improving water safety. Questions still exist about whether microsporidia infections remain persistent in asymptomatic immune-competent individuals, reactivate during conditions of immune compromise, or may be transmitted to others at risk, such as during pregnancy or through organ donation. Reliable serological diagnostic methods are needed to supplement polymerase chain reaction or histochemistry when spore shedding may be sporadic.

Topics: Animals; Humans; Microsporidia; Microsporidiosis

PubMed: 16940873
DOI: 10.1097/01.qco.0000244055.46382.23

Review

Authors: R Weber, R T Bryan, D A Schwartz...

Microsporidia are obligate intracellular spore-forming protozoal parasites belonging to the phylum Microspora. Their host range is extensive, including most invertebrates and all classes of vertebrates. More than 100 microsporidial genera and almost 1,000 species have now been identified. Five genera (Enterocytozoon spp., Encephalitozoon spp., Septata spp., Pleistophora sp., and Nosema spp.) and unclassified microsporidia (referred to by the collective term Microsporidium) have been associated with human disease, which appears to manifest primarily in immunocompromised persons. The clinical manifestations of microsporidiosis are diverse and include intestinal, pulmonary, ocular, muscular, and renal disease. Among persons not infected with human immunodeficiency virus, ten cases of microsporidiosis have been documented. In human immunodeficiency virus-infected patients, on the other hand, over 400 cases of microsporidiosis have been identified, the majority attributed to Enterocytozoon bieneusi, an important cause of chronic diarrhea and wasting. Diagnosis of microsporidiosis currently depends on morphological demonstration of the organisms themselves. Initial detection of microsporidia by light microscopic examination of tissue sections and of more readily obtainable specimens such as stool, duodenal aspirates, urine, sputum, nasal discharge, bronchoalveolar lavage fluid, and conjunctival smears is now becoming routine practice. Definitive species identification is made by using the specific fluorescein-tagged antibody (immunofluorescence) technique or electron microscopy. Treatment options are limited, but symptomatic improvement of Enterocytozoon bieneusi infection may be achieved with the anthelmintic-antiprotozoal drug albendazole. Preliminary observations suggest that Septata intestinalis and Encephalitozoon infections may be cured with albendazole. Progress is being made with respect to in vitro propagation of microsporidia, which is crucial for developing antimicrosporidial drugs. Furthermore, molecular techniques are being developed for diagnostic purposes, taxonomic classification, and analysis of phylogenetic relationships of microsporidia.

Topics: Animals; HIV Infections; Humans; Microscopy, Electron; Microscopy, Electron, Scanning; Microsporida; Microsporidiosis

PubMed: 7834600
DOI: 10.1128/CMR.7.4.426

Authors: Rodrigo Cruz Choappa

Topics: Microsporidia; Microsporidiosis

PubMed: 29652974
DOI: 10.4067/s0716-10182018000100073

Review

Authors: P S Mohamed Yusoff, E Osman, R Z A Raja Sabudin...

Disseminated microsporidiosis is a life-threatening disease resulting from the haematogenous spread of microsporidia species. The diagnosis is challenging owing to its subtle nonspecific clinical presentation, which usually reflects the underlying organ involved. Therefore, a high index of suspicion is required for early diagnosis. Besides, tools for confirmatory laboratory diagnosis are limited. Currently, there is no direct diagnostic method that can detect the infection without involving invasive procedures. Clinical confirmation of disseminated microsporidiosis is usually based on light and transmission electron microscopy of infected tissue specimens. These are then followed by species detection using polymerase chain reaction (PCR). Disseminated microsporidiosis shows the potential to be cleared up by albendazole or fumagillin if they are detected and treated early. Based on a series of case reports, this review aims to present a current update on disseminated microsporidiosis with emphasis on the clinical manifestations based on the organ system infected, diagnostic approach and treatment of this devastating condition.

Topics: Humans; Microsporidia; Microsporidiosis; Polymerase Chain Reaction

PubMed: 33903300
DOI: No ID Found

Review

Authors: M M Marshall, D Naumovitz, Y Ortega...

Protozoan parasites were the most frequently identified etiologic agents in waterborne disease outbreak from 1991 to 1994. The waterborne parasites Giardia lamblia, Naegleria fowleri, Acanthamoeba spp., Entamoeba histolytica, Cryptosporidium parvum, Cyclospora cayetanesis, Isospora belli, and the microsporidia are reviewed. For each parasite, the review includes history, life cycle, incidence, symptoms, and therapy. Clinical detection methods are compared, and emerging technologies are discussed. Information on the association of these parasites with waterborne outbreaks is reviewed. Current information on protozoan parasites identified as etiological agents in waterborne outbreaks is discussed. Water industry issues related to recent disease outbreaks are examined in the context of water quality testing regulations for G. lamblia and those proposed for C. parvum. The review identifies the limitations of the American Society of Testing and Materials water-testing method for these parasites. An overview of federal regulations affecting the water industry and laboratories that test for water quality is also provided. The article highlights the importance of the clinical laboratory as a frontline defense for the detection of infectious organisms. The review points to the need for clinical laboratories, physicians, and public health personnel to cooperatively plan and assess the challenge of meeting this potential public health threat.

Topics: Acanthamoeba; Amebiasis; Amebicides; Animals; Anti-Infective Agents; Antifungal Agents; Antiprotozoal Agents; Antitrichomonal Agents; Coccidiosis; Cryptosporidiosis; Cryptosporidium parvum; Eimeriida; Entamoeba histolytica; Entamoebiasis; Giardia lamblia; Giardiasis; Humans; Isospora; Microsporida; Microsporidiosis; Naegleria fowleri; Protozoan Infections; Water Microbiology; Water Supply

PubMed: 8993859
DOI: 10.1128/CMR.10.1.67

Review

Authors: Bing Han, Louis M Weiss

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