Microsporidia are unicellular spore-forming eukaryotic parasites. The taxonomic classification of these organisms has been controversial during the past few decades. As molecular phylogenetic data have emerged, classification schemes based on morphologic and physiologic characteristics of these parasites have been reconsidered. In 1857, when Nageli¹⁰ named Nosema bombycis as the causative agent of pepper disease in silkworms, he believed that the organism was a yeast and placed it among the schizomycetes, which were an assortment of both yeasts and bacteria. In 1882, Balbiani¹ recognized these unusual organisms as a distinct group, and he proposed the name microsporidia to accommodate the only known microsporidium at the time, N. bombycis.

As eukaryotes lacking identifiable mitochondria, microsporidia were later considered to be ancient protists that had diverged before the evolution of mitochondria. This theory placed microsporidia together with other amitochondriate protists, and they were collectively known as Archezoa.¹⁰ Early molecular genetic analyses of ribosomal RNA also supported the Archezoan hypothesis, as did the absence of organelles such as peroxisomes and Golgi apparati.

However, further analysis of microsporidian phylogeny contradicts the notion that microsporidia derive from a primitive origin. Recent scientific discoveries, including the sequencing of the full genome of Encephalitozoon cuniculi, support the relation of microsporidia to fungi.^11,12 Rather than emerging from primitive origins, microsporidia may be highly reduced, sophisticated fungi that contained mitochondria at one time.^10,13

Although the first microsporidial organism was not discovered until the mid-1800s, since then approximately 150 genera with more than 1,200 different species have been described within the phylum Microspora. Fourteen microsporidian species have been identified as human pathogens (Table 1): Brachiola algerae, B. connori, B. vesicularum, Encephalitozoon cuniculi, E. hellem, E. intestinalis, Enterocytozoon bieneusi, Microsporidium africanum, M. ceylonensis, N. ocularum, Pleistophora ronneafiei, Trachipleistophora anthropophthera, T. hominis, and Vittaforma corneae. Species from several genera have caused documented ocular infection (Table 1), with E. hellem being the most commonly identified organism in reported cases.

Microsporidia infect organisms of many different types, especially animals. Insects and fish are particularly common hosts for microsporidial infection, but a definitive reservoir of human pathogenic species has not been identified. The prevalence and distribution of microsporidiosis in humans is not fully known. Factors that limit our understanding of the epidemiology of microsporidiosis include subclinical infection, diagnostic inconsistency, diverse clinical manifestations of disease, nonrandom study design, and uncertain sources of transmission.