Microsporidia are widely recognised pathogens in both invertebrates and vertebrates. Microsporidia belong to the phylum Microsporidia, with more than 144 genera and 1200 species[1, 2]. The most common human pathogens are: Encephalitozoon, Enterocytozoon, Pleistophora and Nosema.
Microsporidia are small (1.5-2.5 μm × 2.5-4 μm), oval shaped, obligate intracellular microorganisms found in epithelial and endothelial cells, fibroblasts, macrophages, astrocytes[1, 2]. Although their human pathogenic potential has been reported, they have become increasingly recognized as opportunistic pathogens with the advent of the AIDS epidemic. Initially, Enterocytozoon bieneusi was identified as a cause of diarrhoea and Encephalitozoon (E.) intestinalis (formerly Septata intestinalis), and E. cuniculi for diarrhoeal or disseminated illnesses[2, 3].
Microsporidial hepatitis, sclerosing cholangitis, peritonitis, cardiac, sinusal, urinary, pulmonary, renal or ocular involvement have been reported. Microsporidia have been detected in clinical samples from intestines, livers, muscles, corneas, kidneys, adrenals, gonads, ganglia, small arteries, biliary tracts, urine, sinuses, and brain[4, 5]. Whereas the incidence of microsporidiosis has decreased in HIV-infected people since the availability of cART, this infection has been increasingly reported in non-HIV-infected individuals, such as solid organ and bone marrow transplant recipients, as well as in cancer, diabetic and elderly patients. Furthermore, microsporidiosis has even been reported in immunocompetent persons[6, 7] and in solid organ transplant recipients of latently infected donors. We decided to report this case 12 years later because of this new emerging evidence and increased interest. Moreover, we now seek to alert physicians to potentially include microsporidiosis in the differential diagnosis not only in HIV-infected patients.
Cerebral microsporidiosis was first reported in 1959 [cited by reference and 12 cases due to E. cuniculi, all in HIV-infected persons, can be found in the medical literature from 1991 to 1998. Several other cases were described in immunosuppressed, transplant recipients and HIV-infected individuals[6, 10]. In addition, one case was reported in an immunocompetent patient, displaying hemiparesis and epilepsy. Some diagnosed patients benefited from treatment with albendazole, which is active against E. cuniculi.
In this case report, cerebral microsporidiosis was documented post mortem by morphologic examination of brain samples. Interestingly, this diagnosis was not initially considered when the patient was living. The patient presented with no other clinical manifestations such as diarrhea, keratoconjunctivitis, sinusitis, cholangitis, hepatitis, renal injury, which may have suggested a microsporidial infection. In addition, his CD4+ count at admission and 2 months prior was greater than 330 cells/μL in the absence of antiretroviral therapy. Moreover, the brain CT-Scan and MRI findings were suggestive of PML.
Unfortunately, no tests for microsporidia were performed and no treatment was initiated while the patient was living, thus, there was no logical reason to suspect microsporidiosis. At necropsy, no other techniques, such as tissue culture, monoclonal antibodies staining, PCR amplification of ribosomal RNA or DNA were performed to identify and characterize the implicated microsporidian species.
It is unclear as to how and when the patient acquired this infection. Microsporidiosis can be transmitted by a respiratory route, contaminated water or food, contact with animals (such as dogs and rabbits), birds, invertebrates or by contact with an infected person. In spite of well-preserved CD4+ counts and CD4+/CD8+ ratios, this patient presented with diminished CD16+56+ cell counts (10–60 cells/μL; normal 130–700) - the main subpopulation of natural killer (NK) cells. This reduced cell count may have, in part, contributed to his illness. Unfortunately, this finding was not considered during his hospitalisations. Although the T-cell mediated responses are the main protective mechanisms against microsporidiosis, the NK cells may contribute to the immune response and control of this infection.
There is growing evidence that latent microsporidiosis is common in immunocompetent individuals and could, therefore, be reactivated during immunosuppression, such as in HIV-infected and immunosuppressed persons, the elderly, transplant recipients, as well as in patients with malignancies or diabetes[6, 14]. It is, therefore, possible that our patient experienced a reactivation of latent microsporidiosis that he had acquired before becoming HIV-infected. The diminished CD16+56+ cell counts may likely be responsible, at least in part, for the reactivation.
We would suggest that cerebral microsporidiosis should be considered in the differential diagnosis of brain lesions in HIV-infected as well as in other immunossupressed patients or transplant recipients, particularly when the etiology is unknown. We would suggest that urinary and CSF specimens should be submitted for detection of Microsporidia. A pre-emptive treatment with albendazole may be considered when the brain lesions do not improve despite optimal HIV control, improved immunity and treatment for other suspected brain lesions.
Collectively, given the ubiquitous nature of microsporidia; their multiple routes of transmission; the potential that a latent infection may be reactivated or transmitted through donated organs; and the multitude of clinical manifestations, this infection should be considered in the differential diagnosis, when no definite etiology is established.
Written informed consent for autopsy was obtained from his mandatory and friend, the only next of kin to the patient. A copy of the written consent is available for review by the Editor-in-Chief of this journal. At the time of manuscript writing (11 years after patient’s death) we were unable to identify an individual from whom to seek consent for publication. We informed the Ethical Research Committee and a waiver was granted for consent to publish this case report.