Differential recognition and cytokine induction by the peptidorhamnomannan from Sporothrix brasiliensis and S. schenckii

Sporotrichosis is a deep mycosis caused by dimorphic species of the genus Sporothrix, with differences in pathogenicity between S. schenckii and S. brasiliensis species. Recently, it was discovered that the cell wall peptidorhamnomannan (PRM) of Sporothrix spp . is a pathogen associated molecular pattern (PAMP). Interestingly, S. brasiliensis PRM has additional unknown rhamnose residues. We hypothesize that the structural differences of Sporothrix spp PRMs impact the host's immune response and may explain the severity of sporotrichosis caused by S. brasiliensis. Here we demonstrate that S. brasiliensis yeasts and its PRM (S.b PRM) induced a strong inflammatory response in human PBMCs, with high production of TNF-α, IL-6 and IL-1β and induction of T-helper cytokines IFN-γ, IL-17 and IL-22. In contrast, S. schenckii yeasts and its PRM induced higher concentrations of interleukin-1 receptor antagonist (IL-1Ra), which resulted in low production of T-helper cytokines such as IL-17 and IL-22. CR3 and dectin-1 were required for cytokine induction by both PRMs, while TLR2 and TLR4 were required for the response of S.s PRM and S.b PRM, respectively. IL-1β and IL-1α production induced by S. brasiliensis yeasts and S.b PRM were dependent on inflammasome and caspase-1 activation. S. schenckii and S.s PRM were able to induce IL-1β independent of ROS. In conclusion, these findings improve our understanding of the pathogenesis of Sporothrix spp. by reporting differences of immunological responses induced by S. schenckii and S. brasiliensis. The study also opens the gateway for novel treatment strategies targeting local inflammation and tissue destruction induced by S. brasiliensis infection through IL-1 inhibition.

Paracoccidioidomycosis in an Elderly Simulating Cholangiocarcinoma

Paracoccidioidomycosis, the most prevalent deep mycosis in Latin America, is caused by dimorphic species of the genus Paracoccidioides, affects predominantly male rural workers between 30-50 years of age and is an important cause of morbidity and mortality. It can present in two clinical forms: acute/subacute or chronic. In rare cases paracoccidioidomycosis may simulate neoplasia and must be considered as a differential diagnosis of intra-abdominal tumors in endemic areas. We report an exuberant case of subacute paracoccidioidomycosis in an elderly lady, although it is more frequent in the juvenile form. Multiple facial skin lesions were associated with a wasting syndrome and extensive adenopathy including in the hepatic area, causing bile duct dilatation simulating a cholangiocarcinoma. Skin histopathology was diagnostic and antifungal treatment allowed complete resolution of cutaneous and systemic lesions, thus highlighting the merit of the dermatologist, who was fundamental for the conclusive diagnosis and institution of specific therapy, resulting in a favorable outcome.

Aspergillus Section Fumigati Pneumonia and Oxalate Nephrosis in a Foal

Equine pulmonary aspergillosis is a rare deep mycosis often due to the hematogenous spread of hyphae after gastrointestinal tract disease. We describe herein the main clinic-pathological findings observed in a foal, which spontaneously died after showing diarrhea and respiratory distress. Necropsy and histopathological investigations allowed to diagnose pulmonary aspergillosis, which likely developed after necrotic typhlitis-colitis. Biomolecular studies identified Aspergillus section Fumigati strain as the causative agent. Notably, severe oxalate nephrosis was concurrently observed. Occasionally, oxalate nephropathy can be a sequela of pulmonary aspergillosis in humans. The present case report suggests that the renal precipitation of oxalates can occur also in horses affected by pulmonary aspergillosis and could likely contribute to the fatal outcome of the disease.

Eumycetoma Osteomyelitis Calcaneus in Adolescent; Report of Case and Review in Literature.

Background: Mycetoma is the most common deep mycosis in humans. It is a chronic, progressive, and destructive disease primarily caused by actinomycetes (98%). It involves the skin, soft tissues and occasionally bone, central nervous system as well as internal organs, and characterized by formation of black grains and poor response to treatment. Case presentation: We present a case report about 19 year old male patient with annoying Right ankle pain and swelling for more than 1 year. Diagnosed initially as abscess and drainage was done 8 months ago without any improvement. No X-ray, biopsy or swab for culture and sensitivity done at time of first presentation. On his current presentation at Omdurman hospital mycetoma foot with osteomyelitis was diagnosed based on radiological and pathological assessment. Patient treated with aggressive debridement and bone curettage plus postoperative Itraconazole for 1 year. Conclusion: Surgical Debridement with aggressive bone curettage followed by regular follow up and X-ray can improve the prognosis and achieve good surgical outcome with very low risk of recurrence.

Possibility of Japanese Cedar Pollen Causing False Positives in the Deep Mycosis Test

Because Japanese cedar pollen (JCP) contains beta-1,3-d-glucan (BG), there is concern that its lingering presence in the atmosphere, especially during its scattering period, may cause false positives in the factor-G-based Limulus amebocyte lysate (LAL) assay used to test for deep mycosis (i.e., G-test). Hence, we examined whether the LAL assay would react positively with substances contained in JCP by using the G-test to measure JCP particles and extracts. BG was purified from the JCP extract on a BG-specific affinity column, and the percentage extractability was measured using three different BG-specific quantitative methods. The G-test detected 0.4 pg BG in a single JCP particle and 10 fg from a single particle in the extract. The percentage extractability of JCP-derived BG was not significantly different among the three quantitative methods. As the JCP particles should technically have been removed during serum separation, they should be less likely to be a direct false-positive factor. However, given that the LAL-assay-positive substances in the JCP extract were not distinguishable by the three BG-specific quantitative methods, we conclude that they may cause the background to rise. Therefore, in Japan false positives arising from JCP contamination should be considered when testing patients for deep mycosis.

Chasing the culprit in shadow – Sinonasal mucormycosis in an immunocompetent host

Rhino-orbital mucormycosis is an uncommon, rapidly progressive, fulminant, angio-invasive deep mycosis usually affecting individuals with underlying immunosuppression, the most common being diabetes mellitus. In such, the course may be fatal with dissemination. Early detection with control of underlying predisposing conditions is critical with respect to the prognosis. Rarely, mucormycosis may develop in an immunocompetent host, when its non-specific symptomatology and inconspicuous radiological findings may obscure its diagnosis. Any delay in treatment predisposes to multi-organ morbidity and potential mortality. We present an immunocompetent adult with no underlying predisposing illness who was harbouring invasive sinonasal mucormycosis causing orbital cellulitis. A high index of suspicion is mandatory.

DIAGNOSTIC AND TREATMENT DIFFICULTIES OF SPOROTRICHOSIS

Introduction. Sporotrichosis is a deep mycosis caused by the dimorphic fungus Sporothrix schenckii and arises from traumatic inoculation of fungus conidia into damaged skin from plants and other organic material. The objective. In order to prevent diagnostic mistakes, which leads to a long-term and ineffective treatment we presented a clinical case of the sporotrichosis, a rare skin disease in our country, that arose in an elderly patient after a rose injury. Methods. The diagnosis of sporotrichosis of the skin was established by the clinical data, anamnesis and histologic examination. Results The impossibility of long-term administration of systemic antifungal drugs in an adequate dose in this case, required to find out an alternative methods of treatment without systemic side effects. The use of local radiation therapy in a patient with skin sporotrichosis led to a positive result in this clinical case. Conclusions. Diagnostic difficulties and the problems of the treatment require awareness of dermatovenereologists and use of alternative methods of treatment.

Evaluating Candida albicans biofilm formation in silkworms

Candida albicans is a pathogenic fungus that causes deep mycosis in immunocompromised patients and forms a biofilm on catheter surfaces. Here we showed that C. albicans infection of silkworms led to biofilm formation on the surface of polyurethane fibers, a catheter substrate material, while inside the silkworm body. Silkworms inserted with polyurethane fibers survived for at least 48 hours. When silkworms inserted with polyurethane fibers were subsequently infected with C. albicans, biofilm formed on the surface of the polyurethane fiber within 24 hours in the silkworm body. These results suggest that silkworms can be used to evaluate C. albicans biofilm formation.