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Encephalitozoon
Published in Dongyou Liu, Handbook of Foodborne Diseases, 2018
Alexandra Valencakova, Lenka Luptakova, Monika Halanova, Olga Danisova
During a microsporidial keratoconjuctivitis and ocular microsporidiosis, a local therapeutic agent called fumagillin is recommended and applied.80 Fumagillin is an antiangiogenetic factor containing an antibiotic derived from Aspergillus fumigatus. Fumagillin and its semisynthetic analogue TNP-470 exert their effect by binding to the metalloprotease methionine aminopeptidase type 2 (MetAP2) of the pathogen and inhibiting its activity. Clinical manifestations are alleviated in less than 1 week, but for the complete elimination of the pathogen, or to prevent the recurrence of infection, a long-term application of the drug is necessary.
Fumagillin
Published in M. Lindsay Grayson, Sara E. Cosgrove, Suzanne M. Crowe, M. Lindsay Grayson, William Hope, James S. McCarthy, John Mills, Johan W. Mouton, David L. Paterson, Kucers’ The Use of Antibiotics, 2017
Fumagillin is an amebicide and anti-infective agent first isolated in 1949 from the fungus Aspergillus fumigatus (Anderson, 1952). It is water insoluble. The chemical formula is C26H34O7; the molecular weight is 458.6, its chemical structure is shown in Figure 188.1.
Enterocytozoon bieneusi
Published in Dongyou Liu, Laboratory Models for Foodborne Infections, 2017
Hirotake Mori, Aongart Mahittikorn
Albendazole, a benzimidazole drug used to treat of a variety of parasitic infections, is highly active against Encephalitozoon species, but has shown only limited efficacy against E. bieneusi. When albendazole is used in patients infected with E. bieneusi, diarrhea may improve in some patients, but the excretion of the organism continues and diarrhea exacerbates rapidly after discontinuation of the drug.97–99 Albendazole works by binding to β-tubulin, and variations in the amino acid sequence of E. bieneusi β-tubulin may be related to clinical resistance.100 Fumagillin, originally isolated from Aspergillus fumigatus, is an antimicrobial agent that is effective against E. bieneusi and Entamoeba histolytica. Fumagillin has successfully treated E. bieneusi infection in AIDS and transplant patients.101,102 The main toxicity is thrombocytopenia, which is reversible after cessation of treatment. However, more severe side effects, such as aseptic meningoencephalitis, have also been reported.103
Stromal Keratitis with Endophthalmitis Caused by Vittaforma Corneae in an Immunocompetent Patient: A Case Report
Published in Ocular Immunology and Inflammation, 2019
Lalida Pariyakanok, Vannarut Satitpitakul, Prasart Laksanaphuk, Kitiya Ratanawongphaibul, Chaturong Putaporntip, Somchai Jongwutiwes
After treatment with hourly topical fumagillin 1.0% eyedrops and oral albendazole 800 mg/day for 10 days, no sign of improvement was observed (Figure 1A). Therapeutic penetrating keratoplasty was done. The therapeutic corneal donor had peripheral epithelial defect of 0.5 × 0.5 mm, no stromal edema with corneal endothelial cell count of 3040 cells/mm2. Serological tests including anti-HIV, nucleic acid amplification testing, HBsAg, anti-HCV, and rapid plasma reagins were negative. Histopathology of recipient corneal button also confirmed the diagnosis of microsporidial stromal keratitis. Polymerase chain reaction (PCR) targeting the small subunit (SSU) rRNA gene of microsporidia spanning 589 bp yielded positive results for templates extracted from corneal tissues.
Therapeutic targets for the treatment of microsporidiosis in humans
Published in Expert Opinion on Therapeutic Targets, 2018
A study of polyamine metabolism in preemergent spores of Enc. cuniculi revealed that microsporidia are reliant on uptake and interconversion of polyamines, rather than synthesis, for maintaining polyamine levels, which makes it possible to use polyamine analogs as a drug for the treatment of microsporidia [165]. Several polyamine analogs have demonstrated activity against microsporidia in vitro and in a murine microsporidiosis model. Bis-ethylated 3-3-3 (bis-ethylnorspermine) or 3–4-3 (bis-ethylhomospermine) derivatives were effective in inhibiting microsporidia growth, but also had host cell toxicity [166]. Another class of polyamine analogs evaluated for the activity against microsporidia was 3-7-3 derivatives. Bis-phenylbenzyl-substituted 3-7-3 (i.e. 1.15-bis N-[o-(phenyl)benzylamino-4,12-diazapentadecane [BW-1]) was found to inhibit Enc. cuniculi PAO activity160. Second generation alkyl-substituted polyamine analogs containing a 3-7-3 polyamine back bone were synthesized and several of these compounds had activity against microsporidia both in vitro, without producing overt cytotoxicity in their host cells, and in vivo in a murine infection model [167]. The novel synthetic polyamines SL-11158 and SL-11144 were also active against Enc. cuniculi both in vitro and in vivo [168]. In addition, another three polyamine analogs were tested in an Ent. bieneusi infection and were compared with the activity of fumagillin. Two of the analogs PG-11302 and PG-11157 had efficacy against Ent. bieneusi infection and were more potent drugs against Ent. bieneusi infection than fumagillin [169].