Treatment of experimental sporotrichosis in mice

Summary Griseofulvin, Amphotericin B, Trichomycin and Potassium Iodide did not influence the course of experimental sporotrichosis with an infective dose of 2.3×10⁵ cells injected intravenously.This research was in part supported by grant E-576 of the U. S. Public Health Service and a grant from McNeill Laboratory, Incorporated, Philadelphia, Pa.     

Effect of potassium iodide on the immune response in the sporotrichosis.

Potassium iodide (KI), the specific treatment for sporotrichosis, apparently does not have a direct action on Sporothrix schenckii. The spontaneous healing and the variability of the clinical presentation in the disease have strengthened the idea that the KI rather interacts with the immune response of the host. The phagocytic process is inefficient in individuals with sporotrichosis in whom the microbicidal mechanism of halogenation fails to control the disease. There is evidence that blocking of free radicals decreases in the presence of KI. Humoral and cellular immunity are present in sporotrichosis but its participation is uncertain; it is yet to be determined if in this mycosis the KI influences other processes or factors of immune response.     

Esporotricosis: prevalencia,perfil clínico y epidemiológico en un centro de referencia en Colombia

BackgroundSporotrichosis is a subacute and chronic infection caused by Sporothrix schenckii, which affects humans and other mammals. Clinical and epidemiological information in Colombia is scarce.ObjectiveTo describe clinical and socio-demographic findings and diagnostic tests in patients with sporotrichosis from 1996 to 2005 in a national reference center in Colombia, and to determine the institutional prevalence from 2002 to 2005.Material and methodsThis was a prevalence study, including patients with clinical diagnosis of sporotrichosis and at least one of the following criteria: positive culture with S. schenckii, pathologic diagnosis suggestive of sporotrichosis, or response to treatment with potassium iodide.ResultsSixty cases were included, 67% were male, and 25% of them were farmers. The most affected anatomical areas were the forearms and hands (32.5% and 22.8% respectively). Most cases came from the Cundinamarca and Boyacá areas. The cases presented as fixed cutaneous sporotrichosis and lymphangitic sporotrichosis. Differential diagnoses with: leishmaniasis and chromoblastomycosis were performed in most of the cases. All patients were treated with potassium iodide. The prevalence for our center from 2002 to 2005 was 8 cases per 100,000 patients.ConclusionsThe characteristics of our patients are similar to those described in other populations, with some differences. The culture continues to be the gold standard for diagnosis purposes. Potassium iodide is the treatment of choice in our center.     

孢子丝菌病43例临床分析

目的 探讨孢子丝菌病的发病原因及特点。方法 就1991～2002年间在本院就诊的深部真菌病病例,利用沙氏真菌学检查方法筛查确诊为孢子丝菌病43例并进行临床观察。结果 1991—1993年患者5例（11．63％）,1994～1996年水灾后2年内患者34例（79．07％）,1997～2002年5年内患者4例（9．30％）。有明显外伤史及疑似蚊、蜂叮螫者占总发病人数72．09％。伴高血压者占20．93％。碘化钾治愈率100％。结论 各种原因造成的环境污染或某些自然灾害致使腐生菌大量生长繁殖是引起本病区域性流行的根本原因。外伤及昆虫叮、螫为重要致病条件。碘化钾为首选治疗药物。     

Comparative Study of 250 mg/day Terbinafine and 100 mg/day Itraconazole for the Treatment of Cutaneous Sporotrichosis

Abstract  

Itraconazole is currently used for the treatment of cutaneous sporotrichosis. Terbinafine at a daily dose of 250 mg has been successfully applied to the treatment of cutaneous sporotrichosis.     

沈阳地区孢子丝菌病48例临床分析

目的探讨孢子丝菌病的发病原因、特点、诊断及治疗。方法对48例孢子丝菌病病例进行调查分析,全部行真菌学检查,部分行病理检查,采用碘化钾、特比萘芬或以碘化钾为基础的联合治疗。结果48例患者有明确外伤史,蚊虫叮咬病史者占总发病人数66.67%。单纯应用碘化钾或以碘化钾为基础的联合治疗8~12周,治愈率均达100%。结论外伤及昆虫叮咬、动物抓伤为本病的重要致病诱因,单纯应用碘化钾或特比萘芬均可治愈,但联合用药起效更快,效果更好。     

Diagnosis and Treatment of Lymphocutaneous Sporotrichosis: What Are the Options?

Lymphocutaneous sporotrichosis is the most common clinical form of cutaneous sporotrichosis. Caused by a complex of dimorphic fungi called Sporothrix schenckii complex, it is an occupational disease, present especially in tropical and subtropical areas, and has been reported in all continents. Diagnosis is established by isolation of the causative agent. Therapy of choice for lymphocutaneous sporotrichosis is itraconazole, and in developing countries, potassium iodide solution. In general, the lymphocutaneous form is considered a mild benign form of the disease, and the majority of cases respond well to treatment in about 3–4 months of therapy. In this paper, we have made a general review of the disease, especially of the epidemiology, clinical features and diagnosis of the lymphocutaneous form, as well as a brief analysis of the advantages and disadvantages of diverse treatments.     

Successful Treatment of Canine Sporotrichosis with Terbinafine: Case Reports and Literature Review

Sporotrichosis occurs worldwide, and the metropolitan region of Rio de Janeiro, Brazil, is a main endemic area, with a large number of human and animal cases in the last 19 years. This mycosis is more frequently described in cats rather than in dogs. There are a limited number of oral antifungal agents for the treatment of sporotrichosis in animals. In this context, the effectiveness of terbinafine in the treatment of sporotrichosis in humans, as well as the promising results of in vitro susceptibility tests, inspired us to use this drug in the therapy of this mycosis in dogs. We reported for the first time the use of terbinafine in the treatment of two dogs with sporotrichosis caused by Sporothrix brasiliensis. Moreover, we provided an overview of therapeutic features of canine sporotrichosis cases reported since the 1960s. One of the dogs presented the fixed cutaneous form of the disease, while the other patient presented hyperemia of the nasal mucosa and respiratory signs only. Terbinafine showed high antifungal activity in vitro against the canine Sporothrix isolates. The dogs were successfully treated with terbinafine, with remission of all clinical signs initially presented. The current reports indicate that this drug can emerge as a therapeutic option for canine sporotrichosis.     

Diagnostic performance of mycologic and serologic methods in a cohort of patients with suspected sporotrichosis

BackgroundThe gold standard for the sporotrichosis diagnosis is culture; however, serologic approaches have been recently implemented to aid in the sporotrichosis diagnosis. Nevertheless, the clinical consequences of the introduction of serologic tests are poorly addressed.AimsTo correlate the results of culture and serology of patients with suspected sporotrichosis.MethodsA retrospective study of 198 patients with suspected sporotrichosis was conducted. Information about culture isolation of Sporothrix from clinical samples and antibody detection by an enzyme-linked immunosorbent assay (ELISA) were obtained from the medical records of the patients.ResultsPositive culture and antibody detection was observed in the samples of 84 patients (42.4%). Forty-one samples (20.7%) showed negative results with both techniques and divergent results were obtained in the samples of 73 patients (36.9%). False negative results in the ELISA were observed with 23 patients (31.5%), 78.3% of them with less than 30 days of infection (p = 0.0045). Among the initial false positive ELISA in the sera of 50 patients, four samples in culture yielded the growth of Sporothrix, and 27 improved with itraconazole. At the end of follow-up, a diagnosis of proven or probable sporotrichosis was established in 139 patients, and possible sporotrichosis in 11 patients. The treatment of the patients with probable sporotrichosis with antifungal drugs resulted in clinical cure for these individuals.ConclusionsThese two techniques are complementary in the diagnosis of sporotrichosis, making diagnosis and clinical decision more precise.     

难治性孢子丝菌病1例

报道1例因非医嘱习惯性口服激素导致的难愈性孢子丝菌病。患者右腕木屑刺伤后,出现局限性红斑伴破溃,曾多次外院就诊,诊断为“孢子丝菌病”,给予抗真菌治疗半年后病情仍不断恶化,遂来我院就诊。皮损经真菌镜检、培养及分子生物学测序均鉴定为孢子丝菌病,病理示感染性肉芽肿。询问病史时发现患者有日常口服激素的习惯,嘱患者停用激素并口服伊曲康唑4个月后治愈。     

Sporotrichosis Successfully Treated with Terbinafine and Potassium Iodide: Case Report and Review of the Literature

Sporotrichosis is rare in Turkey. We report a 40-year-old woman who had subcutaneous sporotrichosis caused by sporothrix schenckii that was successfully treated with terbinafine (250 mg, twice a day) for a period of 6 months. She received a saturated solution of potassium iodide orally for two months. Terbinafine and potassium iodide are suggested to be the agents of choice for treatment of subcutaneous sporotrichosis.     

Hombre de 18 años con síndrome verrugoso tropical: ¿leishmaniasis o esporotricosis?

The tropical verrucous syndrome includes infectious, chronic, and granulomatous skin conditions appearing with plaques, nodules, or ulcers with a warty surface which gives name to the syndrome. It includes forms of chromoblastomycosis, sporotrichosis, paracoccidioidomycosis, lobomycosis, leishmaniasis, and tuberculosis verrucosa cutis with ample distribution in tropical and subtropical areas. The diagnoses may be difficult and confused among them, especially between sporotrichosis and leishmaniasis.Clinical, epidemiologic, intradermal reactions, direct smears, skin biopsies, cultures, immunofluorescence, and PCR are used to differentiate them, although several of these methods are not commonly used.We present an 18-year-old man with extensive verrucous plaques in one knee interpreted by clinic, epidemiology, and biopsy as verrucous cutaneous leishmaniasis. He was treated with Glucantime® for 20 days without improvement. A new biopsy was made that was also interpreted as cutaneous leishmaniasis. The revision of both biopsies showed inflammation with abscessed granulomas and asteroid sporotrichotic bodies at the center of the granulomas that led to the diagnosis of sporotrichosis later confirmed by the fungus culture. The patient responded to the treatment with itraconazole. As clinical and epidemiological findings of leishmaniasis and sporotrichosis can be similar, skin biopsy and other paraclinical studies are necessary to establish a proper diagnosis. The asteroid sporotrichotic body is pathognomonic of this mycosis. We review here the essential concepts of leishmaniasis and sporotrichosis and the criteria to differentiate them.     

Chronic pulmonary sporotrichosis

We report a case of chronic human pulmonary sporotrichosis which was not associated with superficial manifestations involving the skin or lymph nodes. As it is difficult to verify an etiology, it is possible that some undiagnosed pulmonary granulomas could represent pulmonary sporotrichosis of the chronic type. These may have been treated for other diseases, such as a mycobacterial infection as in this case. Since the immunodiffusion test is a simple procedure and is almost always positive in chronic disease, its greater utilization should help in defining this disease more frequently. The skin test, agglutination test and culture are variably useful as documented in the literature.Sporotrichosis is a common mycotic infection which is usually confined to the skin and superficial lymph nodes. In disseminated disease, the lung is very rarely involved. Pulmonary sporotrichosis then represents a second form of primary infection though less common than the lymphocutaneous disease. Scott et al. (18) reported two cases of pulmonary sporotrichosis. Ridgeway et al. (15) at about the same time reviewed the previously reported cases up to 1962 and concluded that 12 of the cases could be accepted as sporotrichosis and added two cases of their own. Subsequently, Siegrist & Ferrington (20) and Trevathan & Phillips (23) each reported a case. Presently, approximately 50 cases have been reported in the United States (1–10, 12, 13, 16). Chronic and acute involvement have been delineated by Ridgeway et al. (15) It is believed that the following case represents one of primary pulmonary sporotrichosis of the chronic type without manifest involvement of other organs.     

The spread of cat-transmitted sporotrichosis due to Sporothrix brasiliensis in Brazil towards the Northeast region

BackgroundSporotrichosis is a worldwide subcutaneous mycosis caused by Sporothrix spp. In the past, this infection was associated with armadillo hunting, horticulturists, miners, and gardeners, being considered an implantation mycosis acquired by plant debris injury. Nevertheless, since the late nineties, it has been considered a zoonotic disease in Brazil. Here we report a case series of 121 patients with cat-transmitted sporotrichosis seen in Northeast Brazil.Methodology/Principal findingsPatient’s demographic, clinical data, and length of treatment were recorded. In addition, a mycological examination and further PCR confirmation of species identification were performed. One hundred and twenty two patients were diagnosed with subcutaneous sporotrichosis from October 2016 to December 2019, while PCR revealed that 71 of them were due to S. brasiliensis. The majority of the individuals were female (n = 86; 70.5%). Patient’s age ranged from 5 to 87 years old. The clinical forms found were lymphocutaneous (58.2%) and fixed cutaneous (39.4%). Interestingly, 115 patients reported previous contact with cats diagnosed with sporotrichosis. Patients were successfully treated with itraconazole and potassium iodide.Conclusions/SignificanceOur study adds important contributions for the investigation of the spread of cat-transmitted subcutaneous sporotrichosis in Brazil, specifically towards the Northeast region of a continental-size country. It will also help clinicians to be aware of the existence and importance to accurately diagnose sporotrichosis and treat patients with this infectious disease in the lowest income region of Brazil.     

Bone sporotrichosis: 41 cases from a reference hospital in Rio de Janeiro,Brazil

BackgroundBone sporotrichosis is rare. The metropolitan region of Rio de Janeiro is hyperendemic for zoonotic sporotrichosis and the bone presentations are increasing.MethodsWe studied a retrospective cohort of 41 cases of bone sporotrichosis, diagnosed from 1999–2016. The inclusion criteria was fungal culture isolation from any clinical specimen associated to bone involvement (radiography and/or computed tomography) compatible with fungal osteomyelitis or histopathological findings of bone material compatible with sporotrichosis. Molecular identification was performed when possible.ResultsMale patients represented 58.5% of the cases, with a cohort median age of 43 years. Immunosuppressive conditions were present in 68.3% of the patients, mostly HIV coinfection (51.2%). Multifocal bone involvement (more than one anatomical segment) was diagnosed in 61% of the patients, while 39% presented unifocal involvement. The bones of the hands were the most affected (58.5%), followed by the feet (41.5%) and tibia (26.8%). Multifocal group was characterized by a higher proportion of males (p = 0.0045) with immunosuppressive conditions (p = 0.0014). Amphotericin B followed by oral itraconazole was the main treatment, with a median time of 16.7 months (1.5 to 99.2 months), and cure of 53.7% of the patients (84.6% of immunocompetent and 39.3% of immunocompromised patients). Sequelae occurred in 12.2% of the patients—amputations (7.3%) and ankylosis (4.9%), while 22% died in the course of the disease. Sporothrix brasiliensis was the causative agent in all the 9 (22%) performed cases.ConclusionsBone sporotrichosis is a chronic, challenging condition with prolonged treatment, often with poor results and sequelae.     

Sporotrichosis in patient with AIDS: report of a case and review

Although sporotrichosis is not an AIDS-defining infection, reports of sporotrichosis in individuals infected with HIV are increasing. We report an unusual case of this co-infection in a man with progressive deep cutaneous ulcerations with numerous pleomorphic yeast cells of Sporothrix schenckii. In addition a review of the literature on this subject was carried out and commented upon.     

Metabolic activity of phagocytes in experimental sporotrichosis

Phagocytosis plays an important role as a protective mechanism against infections, since polymorphonuclear leukocytes (PMN) and macrophages are the first cellular lines opposed to agressive microorganisms. In patients with sporotrichosis a diminished capability of killing engulfed yeast by their PMN has been described, but the origin of this deficiency remains unknown.In this work, partial aspects of the oxidative metabolism of PMN leukocytes and peritoneal macrophages of mongolian gerbils experimentally infected with sporotrichosis were studied. For this purpose the nitroblue tetrazolium (NBT) test as described by Baehner and Nathan (1) and myeloperoxidase activity measured according to Kaplow's method were utilized.The PMN and macrophages of mongolian gerbils infected with sporotrichosis showed increased reduction of NBT when compared with the phagocytic cells of normal ones, as is usually observed in most infections. Myeloperoxidase activity was diminished in both PMN and macrophages, but this diminution was statistically significant only in PMN leukocytes. These results show that part of the oxidative mechanisms of phagocytic cells can be impaired in experimental sporotrichosis, and could be correlated with the diminished fungicidal activity of PMN leukocytes obtained from patients infected with sporotrichosis.     

Proteomics-Based Characterization of the Humoral Immune Response in Sporotrichosis: Toward Discovery of Potential Diagnostic and Vaccine Antigens

Background

Sporothrix schenckii and associated species are agents of human and animal sporotrichosis that cause large sapronoses and zoonoses worldwide. Epidemiological surveillance has highlighted an overwhelming occurrence of the highly pathogenic fungus Sporothrix brasiliensis during feline outbreaks, leading to massive transmissions to humans. Early diagnosis of feline sporotrichosis by demonstrating the presence of a surrogate marker of infection can have a key role for selecting appropriate disease control measures and minimizing zoonotic transmission to humans.

Methodology

We explored the presence and diversity of serum antibodies (IgG) specific against Sporothrix antigens in cats with sporotrichosis and evaluated the utility of these antibodies for serodiagnosis. Antigen profiling included protein extracts from the closest known relatives S. brasiliensis and S. schenckii. Enzyme-linked immunosorbent assays and immunoblotting enabled us to characterize the major antigens of feline sporotrichosis from sera from cats with sporotrichosis (n = 49), healthy cats (n = 19), and cats with other diseases (n = 20).

Principal Findings

Enzyme-linked immunosorbent assay-based quantitation of anti-Sporothrix IgG exhibited high sensitivity and specificity in cats with sporotrichosis (area under the curve, 1.0; 95% confidence interval, 0.94–1; P<0.0001) versus controls. The two sets of Sporothrix antigens were remarkably cross-reactive, supporting the hypothesis that antigenic epitopes may be conserved among closely related agents. One-dimensional immunoblotting indicated that 3-carboxymuconate cyclase (a 60-kDa protein in S. brasiliensis and a 70-kDa protein in S. schenckii) is the immunodominant antigen in feline sporotrichosis. Two-dimensional immunoblotting revealed six IgG-reactive isoforms of gp60 in the S. brasiliensis proteome, similar to the humoral response found in human sporotrichosis.

Conclusions

A convergent IgG-response in various hosts (mice, cats, and humans) has important implications for our understanding of the coevolution of Sporothrix and its warm-blooded hosts. We propose that 3-carboxymuconate cyclase has potential for the serological diagnosis of sporotrichosis and as target for the development of an effective multi-species vaccine against sporotrichosis in animals and humans.     

Infectious arthritis as the single manifestation of sporotrichosis: serology from serum and synovial fluid samples as an aid to diagnosis

Sporotrichosis is a generally cutaneous, granulomatous, chronic and benign infection. Less frequently the disease may affect the joints. Articular involvement is usually characterized by monoarthritis in the absence of systemic symptoms, generally preceded by skin lesions, and frequently affects immunosuppressed individuals. We describe here the case of a healthy patient presenting knee arthritis without skin lesions, diagnosed as sporotrichosis, and treated with oral itraconazole. Serology used in this case was an invaluable tool for the diagnosis of sporotrichosis arthritis lacking skin lesions.     

Sporotrichosis in Children: an Update

Sporotrichosis, a disease caused by the saprophytic, dimorphic fungus Sporothrix schenckii, is currently diagnosed worldwide, especially in some tropical and subtropical areas. The infection usually occurs after traumatic inoculation of soil, plants, and organic matter containing the fungus. Certain activities, such as floriculture, agriculture, mining, and wood exploitation, and zoonotic transmission are associated with the mycosis. In humans, the disease is limited to skin, subcutaneous tissue, and the proximal lymphatic. It occurs commonly as lymphocutaneous or fixed lesions predominantly affect the upper limbs and face, the latter location is frequent in children. However, sporotrichosis in children is uncommonly seen. Data about the disease on this specific group of patients is scanty. The gold standard for diagnosis is culture. Nevertheless, there are other recently added methods (serological, histopathological, and molecular) useful for an accurate diagnosis. Itraconazole is the first choice of treatment for sporotrichosis; however, potassium iodide is also an effective option, mainly in children.