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Pathology of Microsporidia

Dr Sampurna Roy MD

 

                                                                                                                      

 

 

Microspora are obligate intracellular parasites, ranging from 1.5 to 5 micrometer wide and from 2 to 7 micrometer long, and include approximately 80 genera and over 700 species.

They are categorised by the production of unique spores that contain a complex tubular extrusion mechanism by which the infective material , 'sporoplasm', is injected into the host cells.

Since the first case of intestinal microsporidiosis was reported in 1985, numerous cases of microsporidiosis have been reported in immunocompromised patients, especially those in the later stages of human immunodeficiency virus (HIV) infection.

The vast majority of Microspora primarily infect non-human hosts, with only Encephalitozoon , Nosema , Pleistophora and Enterocytozoon infecting human beings.

Two major microsporidia, Enterocytozoon bieneusi and Encephalitozoon or Septate intestinali (Enterocytozoon intestinalis) have been identified in the human gut.

The clinical manifestations of microsporidiosis are diverse and include intestinal, pulmonary, ocular, muscular, and renal disease.

Enterocytozoon bieneusi is particularly prevalent in patients with AIDS and causes chronic diarrhoea.

Recently, this organism was also reported to have caused self-limited travellers' diarrhoea in immunocompetent individuals.

Enterocytozoon Intestinalis was first described in 1992 and infects the small intestine, the biliary tract, the respiratory tract, renal tubules and glomeruli, nasal mucosa , conjunctiva and other organs.

Enterocytozoon bieneusi and Enterocytozoon intestinalis both have a strong predilection for distal duodenum and proximal jejunum.

The colon is rarely involved.

Detection of the organism:  

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.

Microscopic features :   

These two major microorganisms are quite difficult to  detect on routine haematoxylin and eosin stained biopsy specimens, primarily due to their minute size, poor staining quality and lack of associated specific mucosal changes.

The small intestinal mucosa shows a spectrum of degenerative changes that generally parallel the burden of parasites.

The small intestinal mucosa may be normal appearing, but typically shows mild villous blunting, focally increased intraepithelial lymphocytes, crypt hyperplasia and some surface epithelial damage including tufting and vacuolation.

Neutrophils are usually absent.

Enterocytozoon bieneusi:

A tufted and budding arrangement of groups of enterocytes is common in the upper half of the villi with clusters of pseudostratified nuclei and a tendency for these areas to appear tangentially sectioned.

This organism can be identified in normal, but more frequently abnormal, enterocytes over the upper portion of villi (rarely seen below the mid-villus), as small pale haematoxyphilic structures in the supranuclear apical cytoplasm usually surrounded by an artifactual halo, causing nuclear indentation of the enterocytes.

Meronts and sporonts may also be seen by light microscopy as slightly haematoxyphilic against the cytoplasm.

All stages are typically seen in the cytoplasm on the luminal side of the enterocyte. 

The resulting cupping of the associated enterocyte nucleus is a useful clue to diagnosis.

The presence of small slit-like areas within the organism is also a useful diagnostic feature.

Enterocytozoon Intestinalis:

In contrast, it can infect the entire length of villi , even the base of crypts, and appears as clusters of variable refractile bluish bodies in the supranuclear, apical cytoplasm.

The most notable feature is the presence of large numbers of spores within enterocyte vacuoles.

These are identified more easily than Enterocytozoon bieneusi spores as they are slightly larger and more numerous and the pre-spore stages are more harder.

The other feature that differentiates them from Enterocytozoon bieneusi is the presence of spores in macrophages and occasionally free within the lamina  propria , perhaps correlating with its tendency to disseminate.

The upper parts of the villi tend to show greater density of infection and these areas may show focal necrosis and cell sloughing.

Semi-thin resin embedded sections may help in the identification and recognition of the organism.

Both spores are better visualised with Gram, acid fast, periodic acid-Schiff, Giemsa or modified trichrome stains.    

Frazen et al successfully amplified Microsporidian DNA from Enterocytozoon bieneusi in duodenal biopsy specimens. Detection of microsporidia (Enterocytozoon bieneusi) in intestinal biopsy specimens from human immunodeficiency virus-infected patients by PCR.J Clin Microbiol. 1995 Sep;33(9):2294-6.

Encephalitozoon species (Enterocytozoon cuniculi and Enterocytozoon hellum)

Enterocytozoon cuniculi and Enterocytozoon hellum are similar and can only be distinguished by biochemical or immunological methods.

In 1991 the new species Enterocytozoon hellum was characterised after isolation from the eyes of patients with keratoconjunctivitis.

There is systemic spread of these organisms with wide range of organ involvement (Example: Urinary and renal spread, nasal and sinus infection and tracheobronchial tree and lung involvement).

Image1  ; Image2 (Oscar Xavier Hernández-Rodríguez, Octavio Alvarez-Torres, and Norma Ofelia Uribe-Uribe, “Microsporidia Infection in a Mexican Kidney Transplant Recipient,” Case Reports in Nephrology, vol. 2012, Article ID 928083, 4 pages, 2012. doi:10.1155/2012/928083)

                                                

Further reading:

Intestinal microsporidiosis:

A case of Enterocytozoon bieneusi infection in an HIV-negative renal transplant recipient.

Microsporidiosis: molecular and diagnostic aspects.

Detection of Enterocytozoon bieneusi in two human immunodeficiency virus-negative patients with chronic diarrhea by polymerase chain reaction in duodenal biopsy specimens and review.

Microsporidial infections in humans: current practice and developments in laboratory diagnosis.

Human microsporidial infections.

Histological diagnosis of intestinal microsporidiosis in patients with AIDS.


 

 

 


 

 

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