RESUMO
Microsporidia are protists close to the kingdom of fungi that may cause eye infections. Most cases are reported in Asia and affect both immunocompromised and immunocompetent patients. Here, we report a rare case of microsporidial keratoconjunctivitis in an immunocompetent French patient 3 weeks after returning from India. In our patient, Weber trichrome staining of conjunctival scrapings revealed rounded elements approximately 1-3 µm in size. Conventional polymerase chain reaction analysis by ribosomal RNA subunit sequencing showed 100% identity with Vittaforma corneae. Treatment by corneal debridement combined with fluoroquinolone eye drops allowed complete resolution of the lesions. Although rare, ocular microsporidiosis should be investigated in a patient who is native to Asia or has returned from an endemic area and presents with keratoconjunctivitis of undetermined etiology.
Assuntos
Antifúngicos/uso terapêutico , Infecções Oculares Fúngicas/diagnóstico , Fluoroquinolonas/uso terapêutico , Ceratoconjuntivite/diagnóstico , Microsporidiose/diagnóstico , Córnea/efeitos dos fármacos , Córnea/microbiologia , Córnea/patologia , Córnea/cirurgia , Desbridamento/métodos , Infecções Oculares Fúngicas/tratamento farmacológico , Infecções Oculares Fúngicas/microbiologia , Infecções Oculares Fúngicas/cirurgia , França , Humanos , Índia , Ceratoconjuntivite/tratamento farmacológico , Ceratoconjuntivite/microbiologia , Ceratoconjuntivite/cirurgia , Masculino , Microsporidiose/tratamento farmacológico , Microsporidiose/microbiologia , Microsporidiose/cirurgia , Pessoa de Meia-Idade , Viagem , Vittaforma/efeitos dos fármacos , Vittaforma/crescimento & desenvolvimento , Vittaforma/patogenicidadeRESUMO
We amplified, cloned, and sequenced the beta-tubulin gene of Vittaforma corneae, a microsporidium causing human infections. The beta-tubulin gene sequence has a substitution at Glu(198) (with glutamine), which is one of six amino acids reported to be associated with benzimidazole sensitivity. Benzimidazoles were assayed for antimicrosporidial activity and showed poor parasite inhibition.
Assuntos
Antifúngicos/farmacologia , Benzimidazóis/farmacologia , Farmacorresistência Fúngica/genética , Tubulina (Proteína)/genética , Vittaforma/efeitos dos fármacos , Sequência de Aminoácidos , Linhagem Celular , Clonagem Molecular , Fibroblastos/microbiologia , Humanos , Testes de Sensibilidade Microbiana , Microsporidiose/microbiologia , Dados de Sequência Molecular , Análise de Sequência de DNA , Tubulina (Proteína)/química , Tubulina (Proteína)/metabolismo , Vittaforma/genéticaRESUMO
Therapies for microsporidiosis in humans are limited, and fumagillin, which appears to be the most broadly effective antimicrosporidial drug, is considered to be moderately toxic. The purpose of this study was to apply an in vitro drug screening assay for Encephalitozoon intestinalis and Vittaforma corneae and an in vivo athymic mouse model of V. corneae infection to assess the efficacy of TNP-470 (a semisynthetic analogue of fumagillin), ovalicin, and eight ovalicin derivatives. TNP-470, ovalicin, and three of the ovalicin derivatives inhibited both E. intestinalis and V. corneae replication by more than 70% in vitro. Another three of the ovalicin derivatives inhibited one of the two microsporidian species by more than 70%. None of the treated athymic mice survived the V. corneae infection, but they did survive statistically significantly longer than the untreated controls after daily treatment with fumagillin administered at 5, 10, and 20 mg/kg of body weight subcutaneously (s.c.), TNP-470 administered at 20 mg/kg intraperitoneally (i.p.), or ovalicin administered at 5 mg/kg s.c. Of two ovalicin derivatives that were assessed in vivo, NSC 9665 given at 10 mg/kg i.p. daily also statistically significantly prolonged survival of the mice. No lesions associated with drug toxicity were observed in the kidneys or livers of uninfected mice treated with these drugs at the highest dose of 20 mg/kg daily. These results thus support continued studies to identify more effective fumagillin-related drugs for treating microsporidiosis.