Elsevier

Acta Tropica

Volume 94, Issue 1, April 2005, Pages 61-76
Acta Tropica

Microsporidiosis: An emerging and opportunistic infection in humans and animals

https://doi.org/10.1016/j.actatropica.2005.01.010Get rights and content

Abstract

Microsporidia have emerged as causes of infectious diseases in AIDS patients, organ transplant recipients, children, travelers, contact lens wearers, and the elderly. These organisms are small single-celled, obligate intracellular parasites that were considered to be early eukaryotic protozoa but were recently reclassified with the fungi. Of the 14 species of microsporidia currently known to infect humans, Enterocytozoon bieneusi and Encephalitozoon intestinalis are the most common causes of human infections and are associated with diarrhea and systemic disease. Species of microsporidia infecting humans have been identified in water sources as well as in wild, domestic, and food-producing farm animals, raising concerns for waterborne, foodborne, and zoonotic transmission. Current therapies for microsporidiosis include albendazole which is a benzimidazole that inhibits microtubule assembly and is effective against several microsporidia, including the Encephalitozoon species, but is less effective against E. bieneusi. Fumagillin, an antibiotic and anti-angiogenic compound produced by Aspergillus fumigatus, is more broadly effective against Encephalitozoon spp. and Enterocytozoon bieneusi but is toxic when administered systemically to mammals. Gene target studies have focused on methionine aminopeptidase 2 (MetAP2) for characterizing the mechanism of action and for identifying more effective, less toxic fumagillin-related drugs. Polyamine analogues have shown promise in demonstrating anti-microsporidial activity in culture and in animal models, and a gene encoding topoisomerase IV was identified in Vittaforma corneae, raising prospects for studies on fluoroquinolone efficacy against microsporidia.

Introduction

Microsporidia were first identified as the cause of pébrine disease of silkworms in 1857 (Nägeli, 1857). Since then, over 1200 species of microsporidia have been identified as causes of infection in a wide range of invertebrate and vertebrate hosts (Wittner, 1999). Microsporidia were only sporadically identified in humans prior to 1985 and then emerged as causes of opportunistic infections associated with diarrhea and systemic disease in persons with AIDS. As diagnostic methods improved and awareness increased, microsporidiosis also is being detected in organ transplant recipients, children, travelers, contact lens wearers, and the elderly (Bryan and Schwartz, 1999, Schwartz and Bryan, 1999, Deplazes et al., 2000, Didier et al., 2004).

Section snippets

Organism

Microsporidia are nucleated, single-celled, obligately intracellular parasites that were considered to be early-branching eukaryotic organisms based on the presence of prokaryote-like ribosomes, and the apparent absence of true Golgi, peroxisomes, and mitochondria (Vossbrinck et al., 1987, Vavra and Larsson, 1999, Desportes-Livage, 2000). The microsporidia, however, were recently reclassified with the fungi based on observations that include the presence of chitin in the spore wall,

Disease associated with infection

Clinical symptoms and disease associated with microsporidiosis vary with the species causing the infection and the status of the host's immune system. E. bieneusi infections are believed to result most commonly through ingestion of spores with the primary site of infection developing in the epithelial cells (enterocytes) lining the duodenum and jejunum of the small intestine (Fig. 1). Persistent diarrhea, abdominal pain, and weight loss are common clinical symptoms associated with E. bieneusi

Laboratory diagnosis

Serological methods such as immunofluorescent antibody staining, ELISA, and western blot assay have been useful for diagnosing microsporidiosis in immunologically competent laboratory animals such as rodents, rabbits, and carnivores. E. cuniculi is probably the most common microsporidian identified in laboratory animals, and these serological assays relied upon the availability of E. cuniculi organisms that could be grown in culture for generating the required antigens since 1969 (Shadduck, 1969

Epidemiology

Criteria used to characterize a pathogen as a cause of emerging infectious diseases are that a pathogen recently appeared in humans or animals, rapidly increased in incidence, expanded in geographic range, or developed increased or novel mechanisms of resistance (Institute of Medicine and Report, 1992; http://www.iom.edu/report.asp?id=4572). In this context, microsporidia are considered etiologic agents of emerging infectious disease based on the relatively recent discovery of new species of

Therapy and prevention strategies

The two most frequently administered drugs for treating microsporidiosis in animals and humans include albendazole and fumagillin (Conteas et al., 2000, Gross, 2003). Albendazole is a benzimidazole that inhibits tubulin polymerization and also has been used as an anthelmintic and anti-fungal agent. This drug is effective against Encephalitozoon species of microsporidia that infect mammals (including humans), but is only variably effective against E. bieneusi (Kotler and Orenstein, 1999, Conteas

Conclusions

Interest in the microsporidia has grown tremendously during the last 20 years with the recognition of new species that cause opportunistic infections in AIDS patients. New information about the relationship between microsporidia and other organisms led to a change in classification of microsporidia from the protozoa to the fungi, and continued studies on the molecular phylogeny of the microsporidia are likely to identify new drug targets for developing more effective therapeutic strategies. As

Acknowledgments

This work was presented at the Seventh Annual Conference on New and Re-emerging Infectious Diseases, April 15–16, 2004 in Urbana, IL and was funded through grants RR00164 and AI39968 from the National Institutes of Health.

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