Case Report: Coral Reef Pathogen Aspergillus sydowii Causing Black Grain Mycetoma.

Mycetoma is an infrequent subcutaneous infection caused by true fungi (eumycetoma) or aerobic actinomycetes (actinomycetoma). We report the case of a 62-year-old man with eumycetoma involving the left foot and ankle. Skin biopsy revealed black-brown grains, and in culture, a white colony fungus grew at day 8. Molecular sequencing using ITS1-ITS4 primers identified the species as Aspergillus sydowii. The patient was treated with itraconazole 200 mg twice daily and terbinafine 250 mg daily for 8 months, with complete response and no recurrence after 2.5 years of follow-up. Aspergillus sydowii is a saprotrophic fungus that rarely causes skin or nail disease. No cases of eumycetoma caused by this agent have been previously reported. As its geographic distribution continues to expand, it may increasingly be recognized as a cause of human disease.

The Role of Interleukin-1 cytokine family (IL-1ß, IL-37) and interleukin-12 cytokine family (IL-12, IL-35) in eumycetoma infection pathogenesis.

Mycetoma is a neglected tropical disease, endemic in many tropical and subtropical regions, characterised by massive deformity and disability and can be fatal if untreated early and appropriately. Interleukins (IL) -35 and IL-37 are newly discovered cytokines that play an important role in suppressing the immune system. However, the expression of these interleukins in patients with Madurella mycetomatis (M. mycetomatis) induced eumycetoma has not yet been explored. The aim of this study is to determine the levels of IL-1 family (IL-1ß, IL-37) and IL-12 family (IL-12, IL-35) in a group of these patients and the association between these cytokines levels and the patients' demographic characteristics. The present, case-control study was conducted at the Mycetoma Research Centre, Soba University Hospital, University of Khartoum, Sudan and it included 140 individuals. They were divided into two groups; group I: healthy controls [n = 70; median age 25 years (range 12 to 70 years)]. Group II: mycetoma patients [n = 70 patients; median age 25 (range 13 to 70 years)]. Cytokines levels were measured in sera using enzyme linked immunosorbent assay (ELISA). There was a significant negative correlation between IL-1ß and IL-12 levels and lesion size and disease duration, while IL-37 and IL-35 levels were significantly positively correlated with both lesion size and disease duration. The analysis of the risk factors of higher circulatory levels of IL-37 in patients of mycetoma showed a negative significant association with IL-1ß cytokine, where a unit increment in IL-1ß will decrease the levels of IL-37 by 35.28 pg/ml. The levels of IL-37 among the patients with a duration of mycetoma infection ≤ 1 year were significantly low by an average of 18.45 pg/ml compared to patients with a mycetoma infection's duration of ≥ 5years (reference group). Furthermore, the risk factors of higher levels of IL-35 in mycetoma patients revealed a negative significant association with IL-12, as a unit increment in IL-12 decreases the levels of IL-35 by 8.99 pg/ml (p < 0.001). Levels of IL-35 among the patients with duration of mycetoma infection ≤ one year were significantly low on average by 41.82 pg/ml (p value = 0.002) compared to patients with a duration of mycetoma infection ≥ 5 years (reference group). In conclusion, this study indicates that both IL-35 and IL-37 are negatively associated with the levels of IL-1ß and IL-12 in eumycetoma mycetoma infection; and high levels of IL-37 and IL-35 may have a negative impact on disease progression.

Keratinocyte infection by Actinomadura madurae triggers an inflammatory response.

BACKGROUND: Actinomycetoma is a syndrome of the skin characterized by chronic inflammation and lesions with nodular grain-like structures. The most common aetiological agents are Nocardia brasiliensis and Actinomadura madurae. In response to infection with these organisms the body produces an inflammatory immune response in the skin. The aim of the present study was to determine the production of chemokines, pro-inflammatory cytokines, antimicrobial peptides and the expression of Toll-like receptors (TLRs) in keratinocytes infected by A. madurae. METHODS: A cell line of HaCaT keratinocytes was infected with A. madurae at a multiplicity of infection of 20:1 for 2 h and the samples were collected from 2 to 72 h post-infection. Intracellular replication of the bacterium was evaluated by counting of colony-forming units, the TLR expression and antimicrobial peptide production were assayed by confocal microscopy and chemokine and pro-inflammatory cytokine levels were determined by enzyme-linked immunosorbent assay. RESULTS: Early in the infection, A. madurae was able to achieve intracellular replication in keratinocytes, however, the cells eventually controlled the infection. In response to the infection, keratinocytes overexpressed TLR2 and TLR6, produced high concentrations of cytokines monocyte chemoattractant protein-1, interleukin 8, human ß-defensin-1, human ß-defensin-2 and LL37 and low levels of tumour necrosis factor α. CONCLUSIONS: The human keratinocytes contribute to the inflammatory process in response to A. madurae infection by overexpressing TLRs and producing chemokines, pro-inflammatory cytokines and antimicrobial peptides.

Mycetoma: a clinical dilemma in resource limited settings.

BACKGROUND: Mycetoma is a chronic mutilating disease of the skin and the underlying tissues caused by fungi or bacteria. Although recently included in the list of neglected tropical diseases by the World Health Organization, strategic control and preventive measures are yet to be outlined. Thus, it continues to pose huge public health threat in many tropical and sub-tropical countries. If not detected and managed early, it results into gruesome deformity of the limbs. Its low report and lack of familiarity may predispose patients to misdiagnosis and delayed treatment initiation. More so in situation where diagnostic tools are limited or unavailable, little or no option is left but to clinically diagnose these patients. Therefore, an overview of clinical course of mycetoma, a suggested diagnostic algorithm and proposed use of materials that cover the exposed susceptible parts of the body during labour may assist in the prevention and improvement of its management. Furthermore, early reporting which should be encouraged through formal and informal education and sensitization is strongly suggested. MAIN TEXT: An overview of the clinical presentation of mycetoma in the early and late phases, clues to distinguish eumycetoma from actinomycetoma in the field and the laboratory, differential diagnosis and a suggested diagnostic algorithm that may be useful in making diagnosis amidst the differential diagnosis of mycetoma is given. Additionally, a proposed preventive measures which may be helpful in the community is also provided. Since treatment is currently based on expert opinion, we encourage active research to establish treatment guideline for it. CONCLUSION: Since delay in visiting health facility results into gruesome complication, early presentation, recognition and initiation of appropriate choice of regimen is helpful in reducing complications. The clinical overview of mycetoma and the suggested algorithm may enhance suspicion and possibly increase recognition of mycetoma in the community and further guide in differentiation of eumycetoma from actinomycetoma. There is an urgent need for research funding for mycetoma, a disease plagued by severe physical disabilities and social stigma leading to isolation.

[The modern possibilities for the application of multispiral computed tomography in diagnostics of paranasal sinuses mycetomas]. / Sovremennye vozmozhnosti MSKT v diagnostike mitsetom paranazal'nykh sinusov.

The objective of the present study was the analysis of the health status of 20 patients presenting with histologically verified paranasal sinuses mycetomas (fungus balls) with special reference to CT-semiotics characteristic of the fungal ball as early as during the pre-verification period. The surgical strategy for the management of this condition has been substantiated. It is concluded that the final verification of the pathological process in question is possible only based on the results of the histological studies.

White grain mycetoma caused by Scedosporium apiospermum in North India: a case report.

Mycetoma is chronic granulomatous infection of skin and subcutaneous tissue caused by both bacteria and fungi. We report a case of mycetoma caused by Scedosporium apiospermum in the right foot of a 45-year-old farmer in north India. The patient had a history of trauma in the sole of the right foot followed by discharge of white granules along with proximal progression. Scedosporium apiospermum was identified based on colony characteristics and microscopic features on slide culture. Mycetoma is a progressive disease. Foot is commonly affected in persons who walk barefoot, especially in south India. Untreated mycetoma progress and involve the underlying fasciae and tissues along with bones often resulting in loss of limb. By prompt and reliable diagnosis with corresponding antimicrobial administration, we can prevent further progression and limb disability.

Endobronchial cryotherapy for a mycetoma.

Mycetoma is defined as a fungus ball that fills a preexisting lung cavity, most frequently being of tuberculous or sarcoid etiology. The most frequently isolated fungus is the species of Aspergillus, but other fungi such as Fusarium or Zygomycetes can also be present. Most patients lack symptoms. However, presentation may also be with hemoptysis, which can be massive and life-threatening. We describe the case of a 50-year-old man with a history of prior pulmonary tuberculosis, with recurrent episodes of cough and hemoptysis. He was diagnosed to have mycetoma in the left upper lobe cavity. The mycetoma was extracted through bronchoscopy under general anesthesia using a cryoprobe. Treatment was completed with amphotericin B instilled in the cavity and the patient was placed on oral itraconazole. This is the first case report to date in which cryotherapy was used to remove a mycetoma.

Bola fúngica dos seios paranasais: Relato de dois casos e revisão de literatura / Fungus ball of the paranasal sinuses: Report of two cases and literature review

Introdução: Bola fúngica dos seios paranasais é uma infecção não invasiva que se caracteriza por sua cronicidade, sendo a maioria relacionada com tratamento endodôntico prévio. Acomete principalmente o seio maxilar, embora todos os seios possam ser envolvidos. O principal agente etiológico é o Aspergillus spp. A tomografia computadorizada, devido às apresentações radiológicas características, sugere o diagnóstico que é realizado definitivamente através de análises histopatológicas. O tratamento padrão-ouro é a cirurgia sinusal endoscópica com antrostomia meatal média. Objetivo: Relatar dois casos de bola fúngica dos seios paranasais e ressaltar aspectos importantes desta patologia. Relato dos Casos: Caso 1) Paciente do sexo feminino, 78 anos, apresentou-se com queixas de dor facial há 6 meses e história prévia de tratamento endodôntico. Ao exame físico constatou-se a presença de secreção purulenta em meato médio esquerdo. O Raio X apresentou velamento completo do seio maxilar esquerdo, enquanto a tomografia computadorizada mostrou lesão calcificada neste local. Realizou-se sinusotomia que evoluiu bem. Caso 2) Paciente do sexo feminino, 70 anos, procurou atendimento por história de sinusites de repetição. Ao exame físico não se percebeu nenhuma particularidade. A tomografia computadorizada, assim como a ressonância magnética, detectou espessamento da parede mucosa do seio maxilar esquerdo, além de uma massa calcificada. Realizou-se a mesma sequência de tratamento e a paciente também evoluiu bem. Considerações finais: A infecção fúngica deve ser considerada nos pacientes que se apresentam com sinusite crônica, que não respondem ao uso de antibióticos e que possuem história de manipulação endodôntica...

Introduction: Fungal ball of the sinuses is a not invasive infection that if characterizes for its chronicity, being the majority related with previous endodontic treatment. Affect mainly the breasts to maxillary; even so all the breasts can be involved. The main etiological agent is the Aspergillus spp. The computed tomography, had to characteristic the radiological presentations, suggests the diagnosis that is carried through definitively through histopathological analyses. The treatment standard-gold is the sinus surgery with average meatal antrostomy. Objective: Reporting two cases of fungal ball of the sinuses and to stand out important aspects of this pathology. Story of the Cases: Case 1) Patient of the feminine sex, 78 years old, presented itself with complaints of face pain has 6 months and previous history of endodontic treatment. To the physical examination it was evidenced purulent secretion presence in left average meatus. Ray X presented complete veiling of the breasts to maxillary left, while the computed tomography showed injury calcified in this place. Sinusotomy was become fulfilled that evolved well. Case 2) Patient of the feminine sex, 70 years old, looked attendance for history of sinusitis of repetition. To the physical examination no particularity was not perceived. The computed tomography, as well as the magnetic resonance, detected thickening of the mucous wall of the breasts to maxillary left, beyond a calcified mass. It was become fulfilled same sequence of treatment and the patient also evolved well. Final Considerations: The fungal infection must be considered in the patients who if present with chronic sinusitis, that they do not answer to the antibiotic use and that they possess history of endodontic manipulation...

Population-based surveillance for scedosporiosis in Australia: epidemiology, disease manifestations and emergence of Scedosporium aurantiacum infection.

Australia-wide population-based surveillance for scedosporiosis identified 180 cases, with 118 (65.6%) cases of colonization and 62 (34.4%) cases of infection. Predisposing factors for isolation of Scedosporium spp. included chronic lung disease in 37.8% and malignancy in 21.7% of cases. Predictors of invasive disease (n=62) included haematological stem cell transplantation (n=7), leukaemia (n=16) and diabetes mellitus (n=8). Of 183 phenotypically-speciated isolates, 75 (41%) were Scedosporium prolificans (risk factors: haematologic cancer (n=17), neutropaenia (n=14)) and 108 (59%) had Scedosporium apiospermum/Pseudallescheria boydii phenotype [risk factor: diabetes (n=15)]. Scedosporium prolificans (p 0.01) and leukaemia (p 0.03) independently predicted death. Epidemiological and antifungal susceptibility profiles of Scedosporium aurantiacum (prevalence>or=15.8%) and S. apiospermum were similar. No patient with S. aurantiacum infection (n=6) died. This is the first description of clinical features associated with S. aurantiacum.

Pathology of pulmonary aspergillomas.

Aspergilloma refers to a fungal ball formed by saprophytic overgrowth of Aspergillus species and is seen secondary to cavitatory/cystic respiratory diseases. Paucity of clinical and pathological data of aspergilloma in India prompted us to analyze cases of aspergilloma over 15 years. The clinical features were recorded in all and correlated with detailed pathological examination. Aspergillomas were identified in 41 surgical excisions or at autopsy. There was male predominance; half the patients were in their fourth decade. Episodic hemoptysis was the commonest mode of presentation (85.4%). Forty aspergillomas were complex, occurring in cavitatory lesions (82.9%) or in bronchiectasis (14.6%). Simple aspergilloma was seen as an incidental finding in only one. Tuberculosis was the etiological factor in 31 patients, producing cavitatory or bronchiectatic lesions; other causes were chronic lung abscess and bronchiectasis (unrelated to tuberculosis). Surgical resections are endorsed in view of high risk of unpredictable, life-threatening hemoptysis.

Imaging diagnosis--sublumbar pseudomycetoma in a Persian cat.

A 6-year-old Persian cat was examined for constipation, anorexia, and vomiting that was subsequently found to be due to a pseudomycetoma originating from the descending colon and sublumbar region, and causing mechanical obstruction of the colon and rectum. Multiple discrete hyperechoic foci likely representing fungal grains within the lesion gave the mass a coarse echotexture on ultrasound and was supportive of the diagnosis and computed tomography allowed delineation the extent of the mass. A pseudomycetoma is a granulomatous/pyogranulomatous reaction that surrounds dermatophytic fungal hyphae. Definitive diagnosis of a dermatophytic pseudomycetoma requires identification of the etiologic agent by cultivation or immunohistochemical staining. A pseudomycetoma should be included in the differential diagnosis for an abdominal mass in a Persian cat, especially is accompanied by the sonographic findings noted above.

Central nervous system infections by members of the Pseudallescheria boydii species complex in healthy and immunocompromised hosts: epidemiology, clinical characteristics and outcome.

Infections caused by members of the Pseudallescheria boydii species complex are currently among the most common mould infections. These fungi show a particular tropism for the central nervous system (CNS). We reviewed all the available reports on CNS infections, focusing on the geographical distribution, infection routes, immunity status of infected individuals, type and location of infections, clinical manifestations, treatment and outcome. A total of 99 case reports were identified, with similar percentage of healthy and immunocompromised patients (44% vs. 56%; P = 0.26). Main clinical types were brain abscess (69%), co-infection of brain tissue and/or spinal cord with meninges (10%) and meningitis (9%). The mortality rate was 74%, regardless of the patient's immune status, or the infection type and/or location. Cerebrospinal fluid culture was revealed as a not very important tool as the percentage of positive samples for P. boydii complex was not different from that of negative ones (67% vs. 33%; P = 0.10). In immunocompetent patients, CNS infection was preceded by near drowning or trauma. In these patients, the infection was characterised by localised involvement and a high fatality rate (76%). In contrast, CNS infection in immunocompromised patients was presented as rapidly progressive disseminated lesions at various degrees of evolution. Major risk factors for CNS infection were the aspiration of polluted water in near-drowning episodes in immunologically intact patients and medical immunosuppression in the remaining patient groups. As the therapeutic options were poor, the treatment was difficult in general and the prognosis was poor.

Scedosporium apiospermum: changing clinical spectrum of a therapy-refractory opportunist.

Current knowledge on the opportunist Scedosporium apiospermum (teleomorph: Pseudallescheria boydii), generated over a period of more than 120 years, is reviewed. The natural environmental habitat of the fungus is unknown; nutrient-rich, brackish waters like river estuaria have been suggested. The fungus is strongly promoted by agricultural and particularly by industrial pollution.

Genotyping of Madurella mycetomatis by selective amplification of restriction fragments (amplified fragment length polymorphism) and subtype correlation with geographical origin and lesion size.

One of the causative organisms of mycetoma is the fungus Madurella mycetomatis. Previously, extensive molecular typing studies identified Sudanese isolates of this fungus as clonal, but polymorphic genetic markers have not yet been identified. Here, we report on the selective amplification of restriction fragment (AFLP) analysis of 37 Sudanese clinical isolates of M. mycetomatis. Of 93 AFLP fragments generated, 25 were polymorphic, and 12 of these 25 polymorphic fragments were found in a large fraction of the strains. Comparative analysis resulted into a tree, composed of two main (clusters I and II) and one minor cluster (cluster III). Seventy-five percent of the strains found in cluster I originated from central Sudan, while the origin of the strains in cluster II was more heterogeneous. Furthermore, the strains found in cluster I were generally obtained from lesions larger than those from which the strains found in cluster II were obtained (chi-square test for trend, P = 0.03). Among the 12 more commonly found polymorphisms, 4 showed sequence homology with known genes. Marker A7 was homologous to an endo-1,4-beta-glucanase from Aspergillus oryzae, 97% identical markers A12 and B3 matched a hypothetical protein from Gibberella zeae, and marker B4 was homologous to casein kinase I from Danio rerio. The last marker seemed to be associated with strains originating from central Sudan (P = 0.001). This is the first report on a genotypic study where genetic markers which may be used to study pathogenicity in M. mycetomatis were obtained.

Recurrence of Scedosporium apiospermum infection following renal re-transplantation.

Immunosuppression for organ transplantation results in increased susceptibility to opportunistic infections including fungal, such as Scedosporium apiospermum. Even though many reported cases of this infection had both local and systemic manifestations, majority of the systemic infections had a fatal outcome. We report a case of a 50-year-old Caucasian male with lymphocutaneous and presumed pulmonary Scedosporium infection 4 years after renal transplantation that was successfully treated with voriconazole and discontinuation of immunosuppression. He received a second transplant 3 years later in the absence of clinical evidence of S. apiospermum infection. Unfortunately, 4 months after transplantation he developed recurrence of the same infection localizing to the soft tissues. Presently this infection is under control with surgical excision and voriconazole therapy. To our knowledge this is the first reported case of recurrent S. apiospermum infection in a renal transplant recipient. We suggest prophylactic antifungal therapy in all re-transplants with this infection.

A murine model of Madurella mycetomatis eumycetoma.

Eumycetoma due to Madurella mycetomatis is a major mycological health problem in endemic areas. We infected BALB/c mice (male or female) with various amounts of M. mycetomatis mycelium, containing sterilized soil as a natural adjuvant or Freund's incomplete adjuvant. Mice differed with respect to age and immune status. Intraperitoneal, subcutaneous and intravenous inoculation was explored and survival was monitored. Mice were killed at various intervals after inoculation, checked for the presence of the characteristic black grains, and organs were cultured for M. mycetomatis. Infected organs were subjected to histopathological examination. Immunocompetent male mice were as susceptible as immunocompromised female mice, but showed higher mortality rates. In conclusion, a reproducible mouse model of intraperitoneal M. mycetomatis infection with characteristic black grains in immunocompetent adult or young female mice was developed. Although this experimental model does not simulate macroscopic features of the subcutaneous M. mycetomatis infection in humans, the histopathological characteristics of the lesions and the development of black grains are clearly representative for the human infection. This model will enable further studies on the pathogenesis as well as prevention and treatment of the fungal infection.