Essentials of Diagnosis
- Most cases of microsporidiosis occur in male patients with HIV infection and CD4 counts of < 100.
- In HIV-infected patients, microsporidiosis most commonly presents as chronic diarrhea, although cholecystitis, respiratory infection, keratoconjunctivitis, and myositis have also been reported.
- Infections in non-HIV-infected patients are rare but include central nervous system infection, corneal infection, and myositis.
- Diagnosis is difficult and depends on identification of 1- to 2-um spores.
General Considerations
Epidemiology
Microsporidia were first discovered in 1857, but it was not until 1973 that a human case of microsporidiosis was confirmed from a case described in 1959. Awareness of the diversity of microsporidial infections has heightened, especially in light of the AIDS epidemic. Central nervous system, respiratory, corneal, muscular, and gastrointestinal microsporidial infections have all been identified.
Microsporidiosis has been found worldwide. Before the AIDS epidemic, only 10 cases had been reported. Subsequently, hundreds of cases have been recognized, mostly in the United States. Between 23% and 33% of patients with AIDS with chronic diarrhea have been diagnosed with microsporidiosis, with Enterocytozoon bieneusi being the most common culprit. Most cases of microsporidiosis occur in male patients with HIV with severe immunosuppression and CD4 counts of < 100. Of 11 cases reported in non-HIV-infected patients, 4 had other forms of immunosuppression such as earlier liver and bone marrow transplants, and 4 had infections of the cornea, a site that is considered to be immunoprivileged. Infection in immunocompetent patients may be under-recognized because of transient infection or milder disease. Self-limited diarrhea has been documented in an immunocompetent traveler, and an asymptomatic carrier state has been identified.
Little is known about transmission of microsporidiosis, and there have been no reports of common-source outbreaks. However, microsporidium spores have been identified in respiratory secretions, urine, stool, and duodenal aspirates, suggesting that person-to-person transmission may occur by fecal-oral contacts, aerosolized secretions, sexual transmission, or direct corneal inoculation. Microsporidia infect insects, fish, snails, and mammals and are also present in surface water, which suggests the zoonotic and environmental transmission of these resistant spores. The spores have been shown to survive > 1 year in water kept at 4 °C.
Microbiology
Microsporidia are obligate intracellular, spore-forming protozoa of the order Microsporidia and the phylum Microspora. Primitive eukaryotes that lack mitochondria, microsporidia undergo a life cycle with three phases. In the first phase, infection, spores are ingested or inhaled. The host environment stimulates eversion of the spore coat, at which time a coiled tubular apparatus anchors the spore to the host cell. After the spore is attached, it allows the injection of sporoplasm into the cell, which begins the second phase, merogony. Within the cell, the parasite proliferates by fission, creating multiple multinucleated plasmodial meronts. Sporogony, the third phase, occurs when the meront cell matures and its membrane thickens to form a mature thick-walled spore with a diameter of 1-2 um. Cell rupture releases ovoid spores that either reinfect the host or are passed into the environment by urine, stool, or respiratory secretions. These resistant spores can be viable for = 4 months.
Five genera from the protozoan phylum Microspora have been implicated in human disease: Encephalitozoon (Encephalitozoon hellem and Encephalitozoon cuniculi), Pleistophora, Enterocytozoon (Enterocytozoon bieneusi), Septata (Septata intestinalis), and Nosema, which was recently reclassified as Vittaforma. Unclassified species are placed under a sixth taxon, Microsporidium. The genera and species are separated primarily based on the location of the parasite in relation to the host, that is, whether the parasite is in direct contact with host cytoplasm, separated into a vesicle made by the host, or located in a parasitophorous vacuole.
Pathogenesis
Little is known of the etiology of microsporidia. Spores infect epithelia, mesenchymal cells, endothelia, and macrophages. Spores are found in enterocytes with associated intestinal villi shortening, fusion, and crypt elongation, as well as a lymphocytic infiltrate. S intestinalis spreads by lymphatics and blood vessels whereas E bieneusi spreads to the lungs by aspiration. Corneal infection is associated with ulceration, infected epithelium, and an infiltrate of macrophages and neutrophils.