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Functional Defect of Neutrophils Causing Dermatophytosis: Case Report.

ABSTRACT: Background: NADPH-oxidase and myeloperoxidase (MPO) play an important role on defense against pathogenic microorganisms. Defects on these mechanisms have been described in association with recurrent infections due to such as Staphylococcus aureus and Candida albicans. We describe a patient with partial disturbance of intracellular microorganism destruction clinically manifested by recurrent fungal infection. Case report and results: A 58-year-old male rural farmer has suffered with superficial mycosis affecting hands, nails and right ankle persisting for 20 years. He was treated with several antifungal drugs with no improvement. Mycological scraping isolated Trichophyton rubrum. Immunological evaluation showed impaired T cell proliferation to Candidin and impaired neutrophil burst oxidative after specific stimulation with Candida albicans. The patient's DNA was extracted from peripheral blood leukocytes for whole exome sequencing (WES) analysis. Two heterozygous variants of undetermined significance were screened accordingly: (1) MPO A332V (c.995G>A; rs28730837); and (2) NCF1 G83R (c.247G>A; rs139225348). Conclusions: Functional leukocyte evaluation with heterozygous variants in MPO and NCF1 suggest that these defects were associated with the susceptibility to dermatophytosis in our patient. We have developed a fast, effective and safe trial for screening individuals with yeast infections.

SUBMITTER: Constantino-Silva RN

PROVIDER: S-EPMC7712173 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Functional Defect of Neutrophils Causing Dermatophytosis: Case Report.

Constantino-Silva Rosemeire N RN Perazzio Sandro F SF Weidebach Nicolas de Albuquerque NA Grumach Anete S AS

Journal of fungi (Basel, Switzerland) 20201022 4

Background: NADPH-oxidase and myeloperoxidase (MPO) play an important role on defense against pathogenic microorganisms. Defects on these mechanisms have been described in association with recurrent infections due to such as Staphylococcus aureus and Candida albicans. We describe a patient with partial disturbance of intracellular microorganism destruction clinically manifested by recurrent fungal infection. Case report and results: A 58-year-old male rural farmer has ...[more]

PMID: 33105551

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Project description:Dermatophytes are agents of typically benign superficial infections. However, an increasing number of severe infections in immunocompromised hosts has been reported. We aimed to understand the factors underlying the existence of a cohort of patients presenting with chronic widespread dermatophytosis (CWD) due to Trichophyton rubrum, but with no signs of immunodeficiency. Their disease is usually recurrent and difficult to manage. Fourteen patients meeting the following criteria for CWD were studied: T. rubrum culture-proven skin lesions of ?10 cm in at least one dimension; the involvement of at least three non-contiguous localizations of >1 year's duration; and no predisposing conditions. For comparison, we also studied 13 acute Tinea pedis patients. Macrophages and neutrophils were isolated and tested for T. rubrum conidia phagocytic and killing activity. H2O2, NO, and pro- and anti-inflammatory cytokine release were measured. All experiments were run with age- and sex-matched healthy donors' cells in parallel. CWD patients' macrophages and neutrophils presented with reduced T. rubrum-phagocytic and killing abilities, and reduced H2O2 and NO release when compared with those of healthy donors. CWD patients' macrophages secreted lower levels of the proinflammatory cytokines interleukin (IL)-1?, IL-6, IL-8, and tumor necrosis factor (TNF)-?, but enhanced levels of the anti-inflammatory cytokine IL-10. Neutrophil secretion closely followed this unbalanced pattern. In contrast, responses to the positive controls zymosan, lipopolysaccharide, and phorbol myristate acetate were comparable with those of healthy donors. The same experiments were performed with macrophages and neutrophils from the acute Tinea pedis patients and showed no differences when compared with the matched healthy donors. Patients with CWD have a T. rubrum-related functional deficiency of phagocytes and may represent a distinct clinical entity in the complex spectrum of the Trichophyton-host interaction.

Project description:BackgroundThere are thousands of survivors of the 2014 Ebola outbreak in west Africa. Ebola virus can persist in survivors for months in immune-privileged sites; however, viral relapse causing life-threatening and potentially transmissible disease has not been described. We report a case of late relapse in a patient who had been treated for severe Ebola virus disease with high viral load (peak cycle threshold value 13.2).MethodsA 39-year-old female nurse from Scotland, who had assisted the humanitarian effort in Sierra Leone, had received intensive supportive treatment and experimental antiviral therapies, and had been discharged with undetectable Ebola virus RNA in peripheral blood. The patient was readmitted to hospital 9 months after discharge with symptoms of acute meningitis, and was found to have Ebola virus in cerebrospinal fluid (CSF). She was treated with supportive therapy and experimental antiviral drug GS-5734 (Gilead Sciences, San Francisco, Foster City, CA, USA). We monitored Ebola virus RNA in CSF and plasma, and sequenced the viral genome using an unbiased metagenomic approach.FindingsOn admission, reverse transcriptase PCR identified Ebola virus RNA at a higher level in CSF (cycle threshold value 23.7) than plasma (31.3); infectious virus was only recovered from CSF. The patient developed progressive meningoencephalitis with cranial neuropathies and radiculopathy. Clinical recovery was associated with addition of high-dose corticosteroids during GS-5734 treatment. CSF Ebola virus RNA slowly declined and was undetectable following 14 days of treatment with GS-5734. Sequencing of plasma and CSF viral genome revealed only two non-coding changes compared with the original infecting virus.InterpretationOur report shows that previously unanticipated, late, severe relapses of Ebola virus can occur, in this case in the CNS. This finding fundamentally redefines what is known about the natural history of Ebola virus infection. Vigilance should be maintained in the thousands of Ebola survivors for cases of relapsed infection. The potential for these cases to initiate new transmission chains is a serious public health concern.FundingRoyal Free London NHS Foundation Trust.

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Functional Defect of Neutrophils Causing Dermatophytosis: Case Report.

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Functional Defect of Neutrophils Causing Dermatophytosis: Case Report.

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