Comparison of the antifungal activity of the pyrimidine analogs flucytosine and carmofur against human-pathogenic dematiaceous fungi.

Chromoblastomycosis (CBM) and pheohyphomycosis (PHM) are the most common implantation mycoses caused by dematiaceous fungi. In the past, flucytosine (5-FC) has been used to treat CBM, but development of resistance is common. Carmofur belongs to the same class as 5-FC and has in vitro inhibitory activity against the main agents of CBM and PHM. The aim of this study was to compare the action of these two pyrimidine analog drugs against CBM and PHM agents. The minimum inhibitory concentration (MIC) and the selectivity index based on cytotoxicity tests of these two drugs against some agents of these mycoses were determined, with carmofur presenting a higher selectivity index than 5-FC. Carmofur demonstrated here synergistic interactions with itraconazole and amphotericin B against Exophiala heteromorpha, Fonsecaea pedrosoi, Fonsecaea monophora, and Fonsecaea nubica strains. Additionally, carmofur plus itraconazole demonstrated here synergism against a Phialophora verrucosa strain. To evaluate the development of carmofur resistance, passages in culture medium containing subinhibitory concentrations of this pyrimidine analog were carried out, followed by in vitro susceptibility tests. Exophiala dermatitidis quickly developed resistance, whereas F. pedrosoi took seven passages in carmofur-supplemented medium to develop resistance. Moreover, resistance was permanent in E. dermatitidis but transient in F. pedrosoi. Hence, carmofur has exhibited certain advantages, albeit accompanied by limitations such as the development of resistance, which was expected as with 5-FC. This underscores its therapeutic potential in combination with other drugs, emphasizing the need for a meticulous evaluation of its application in the fight against dematiaceous fungi.

Treatment responses in patients with chromoblastomycosis to itraconazole in Madagascar.

INTRODUCTION: Chromoblastomycosis (CBM) is a chronic fungal infection of the skin and subcutaneous tissue caused by several pigmented fungi. It is frequently found in tropical and subtropical areas like Madagascar. This study primarily discusses the effects of antifungal therapy while also describing the epidemiological, clinical, and pathological features of CBM in our patients. METHODS: From March 2013 to January 2019, a descriptive prospective study on CBM patients was undertaken. The study included patients with CBM who had received antifungal treatment for at least 3 months. Itraconazole 200 mg was given to patients every day for ˃3 months. Results were assessed at the 6th and 12th months and classified as major responses, minor responses to treatment, or failure. RESULTS: A total of 29 cases of CBM were included. The mean age of patients was 42.02 years. They primarily worked in rural areas. Infected men were more prevalent. At the end of the 12th month of itraconazole therapy, 3 patients presented major responses, 14 patients had minor responses to treatment, and 12 had been lost to follow-up. The clinical response of CBM to treatment was correlated to the severity and the long course of CBM. When compared with CBM caused by Cladophialophora, CBM caused by Fonsecaea showed a greater clinical response. CONCLUSION: These findings demonstrated that CBM lesions are recalcitrant and difficult to treat.

Chromoblastomycosis (CBM) is a chronic fungal infection of the skin and subcutaneous tissue commonly seen in tropical and subtropical areas. This study mainly discusses the therapeutic while also describing the epidemiological, clinical, and pathological features of CBM in Madagascar.

Chromoblastomycosis in Latin America and the Caribbean: Epidemiology over the past 50 years.

Chromoblastomycosis is a chronic disease caused by melanized fungi that mainly affect individuals performing soil-related labor. The objective of this study was to analyze the epidemiological and clinical characteristics of chromoblastomycosis in Latin America and the Caribbean by an extensive literature review. An integrative review was performed of English, French, Portuguese, and Spanish publications in LILACS, SciELO, PubMed, SCOPUS and Web of Science databases covering the period 1969-2019. A total of 1211 articles were identified, of which 132 were included in the review, covering 2081 patients, 80.3% were males, the mean age was 56.1 years. The mean duration of the disease was 10.8 years. The lesions were mainly described in the lower limbs (60%). The most frequent clinical forms were verrucous (46.4%) and tumorous (21.7%). Major disease symptoms and signs consisted of itching and pain. Bacterial infection and functional limitation were important complications. Immunosuppression post-kidney transplantation was the most frequent comorbidity while leprosy was the main concomitant infectious disease. Fonsecaea pedrosoi and Cladophialophora carrionii were the predominant etiological agents. Majority of the cured cases were treated with itraconazole as monotherapy or in combination with other antifungals, surgery or cryosurgery. Chromoblastomycosis affects hundreds of rural workers in Latin America and the Caribbean, causing disability and personal, family and economic losses. It is important to prioritize epidemiological surveillance and early diagnosis of this disease in order to reveal its real prevalence and direct resources to preventive actions, diagnosis and early treatment. LAY SUMMARY: Chromoblastomycosis is a slowly progressing chronic disease caused by melanized fungi. We collected data from South America and the Caribbean covering 1969-2019, the 132 articles included 2081 patients, mean disease duration was 10.8 years. Fonsecaea pedrosoi and Cladophialophora carrionii predominated.

First report of Veronaea botryosa as a causal agent of chromomycosis in frogs.

A dematiaceous hyphomycete, isolated from frogs, was determined as the possible etiologic agent of a case of systemic chromomycosis this cold-blooded animal. The fungus was identified as Veronaea botryosa on the basis of morphological features observed in histopathological examination and molecular phylogenetic evidence. Although V. botryosa is known to be distributed widely in litter and as a human pathogen, this is the first confirmed report of its involvement in a lethal infection in a cold-blooded animal, including an anuran.

South African report of first case of chromoblastomycosis caused by Cladosporium (syn Cladophialophora) carrionii infection in a cat with feline immunodeficiency virus and lymphosarcoma.

This report describes a 6-year-old neutered male feline immunodeficiency-positive cat with repeated abdominal and thoracic effusions. The cat was diagnosed with and treated for lymphosarcoma but remission was short-lived and, on re-evaluation, a fungal peritoneal exudate was noted. Cytology of the organisms is described and the culture elucidated Cladosporium carrionii, an important cause of chromoblastomycosis. Treatment with itraconazole was unsuccessful in this case.

The clinical presentation and surgical treatment of verrucous dermatitis lesions in a draught horse.

Verrucous pastern dermatitis is a progressive inflammatory skin disease commonly involving the palmar or plantar aspects of the pasterns of horses. There are no reports of successful surgical treatment for multifocal circumscribed verrucous masses in the chronic stages of verrucous pastern dermatitis. A combination of sharp dissection and electrocautery was used to resect numerous multifocal circumscribed verrucous masses from the distal hindlimb of an 11-year-old gelding draught horse. There was no evidence of significant regrowth or complications at a 24 month postoperative examination.

[The goat: approach to an animal model in human chromomycosis]. / El caprino: aproximación a un modelo animal en la cromomicosis humana.

In Falcon State, Venezuela, human chromomycosis is mainly caused by a dimorphic fungus, Cladophialophora carrionii. Xerophytes plants are common in the State and goat breeding in an extensive system as the main way of living. There are not published reports of chromomycosis in goats, despite the fact of their permanent exposition to fungus by accidental inoculation with infected spines. To evaluate parasitic transformation to sclerotic cells, length of fungus-surviving period and histopathological lesions, goats of five months of age were inoculated with 1 x 10(6) cells of C. carrionii by subcutaneous route in the neck and biopsies at 10, 19, 30 and 60 days from inoculated places were performed. Tissues were analyzed by (a) direct test with KOH 10%; (b) inoculation in Saboraud dextrose culture and (c) histopathological techniques. Hyphae and sclerotic cells were observed on tissues treated with KOH 10%; growing of fungus was detected in specific medium up to four weeks post-inoculation. Tissue pathology showed necrotic foci, mixed polymorphonuclear infiltrate, predominance of mononuclear cells, lymphocytes, plasmocytes, cosinophils and giant cells, hyphae and sclerotic cells in each one of samples. C. carrionii caused cellular reactions in goats as those seen in humans at the first stages of infection; however, animals did not develop the typical macroscopic lesions of the human disease.

Spontaneous chromomycosis in the marine toad (Bufo marinus).

Post-mortem examinations were performed on two marine toads, one animal showing neurological disorders and the other multifocal dermatitis. In one case, lesions consisted of a severe granulomatous encephalomyelitis and in the other of multiple granulomas in the nasal cavity, lungs, heart, bone marrow, ovaries and skin. Histologically, the lesions revealed varying amounts of dark brown fungal elements, predominantly sclerotic bodies indicative of a mycotic infection due to a pigmented fungus.

Chromomycosis in a horse.

A 6-year-old Quarter Horse gelding was examined because it had a sharply circumscribed, firm, brown-black, roughly spherical dermal nodule at the right tuber ischii. After it was excised, the lesion did not recur. Microscopically, the dermis of the excised specimen had multiple pyogranulomas, many of which contained thick-walled, dark brown fungal elements, some with internal septation compatible with chromomycotic fungi. Chromomycosis is a rare skin disease in the horse. It may be included in the differential diagnoses of nodular and/or pigmented skin lesions that include melanoma, pyogranuloma, mycetoma, squamous cell carcinoma, habronemiasis, and onchocerciasis.

An outbreak of phaeohyphomycosis in rainbow trout caused by Scolecobasidium humicola.

A previously undescribed host for the opportunistic dematiaceous hyphomycete, Scolecobasidium humicola, is reported. Several epizootics among rainbow trout, Salmo gairdneri, occurred in a Tennessee fish hatchery from 1969 to 1973. Symptoms included surface lesions, blisters and abscesses. The kidneys and other internal organs were invaded by the mycelium of S. humicola. Tissue morphology of the fungus was typical of that associated with phaeohyphomycosis Experimental infections were reproduced in fingerling rainbow trout after intraperitoneal inoculation of S. humicola. Following a change in the hatchery's water supply, no new epizootics have occurred.

Chromomycosis in the toad (Bufo marinus) and a comparison of the etiologic agent with fungi causing human chromomycosis.

Of 75 toads (Bufo marinus) 2 were found infected by black molds. The internal organs of these animals had granulomatous lesions containing brown fungi identical to those found in human chromomycosis. Cultures gave rise to slow-growing black molds but all attempts to induce sporulation failed. The fungi did not grow at 36 degrees C or above and failed to hydrolyse gelatin or casein. Immunodiffusion and immunoelectrophoresis revealed that both isolates were identical and shared common antigens with the recognized human pathogens P. pedrosoi, P. verrucosa and C. carrioni. The findings are compared with other reports of black mold infections in amphibians.