Rhinofacial Conidiobolomycosis: A Case Series and Review of the Literature.

Conidiobolomycosis is an uncommon, chronic, localized subcutaneous mycosis primarily affecting rhinofacial region. It is reported mainly from tropical and subtropical countries. The condition is underreported due to the lack of clinical suspicion and usually mismanaged. This rare mycosis is due to the genus Conidiobolus within the order Entomophthorales of class Zygomycetes. Here we present 3 cases of rhinofacial conidiobolomycosis in otherwise healthy adults from different parts of Sri Lanka over 1-year period. All patients had disfiguring subcutaneous lesions in the rhinofacial area. The diagnoses were based on isolation of Conidiobolus coronatus in clinical specimens.

Conidiobolus lunulus, a new entomophthoralean species isolated from leafcutter ants.

Entomophthoralean fungi with pathogenic abilities to infect social insects are rare. Here, we describe a fungus isolated from leafcutter ants. Morphologically, the fungus has spherical primary conidia and two types of microconidia: one with the same shape as the primary conidia and another with an elliptical to half-moon shape. The fungus also produces villose conidia known previously only from Conidiobolus coronatus. A multilocus phylogenetic analysis was performed with nuc rDNA sequences from three regions (28S, 18S, and internal transcribed spacer [ITS]). Our isolates are distinguished as a new species, described here as Conidiobolus lunulus, and is more closely related to C. brefeldianus than to C. coronatus, despite the greater morphological resemblance to the latter. Morphological differences, unique phylogenetic placement, and isolation from an altogether new host support this finding. This is the first record of an entomophthoralean species isolated from leafcutter ants.

Conidiobolus pachyzygosporus invasive pulmonary infection in a patient with acute myeloid leukemia: case report and review of the literature.

BACKGROUND: Conidiobolus spp. (mainly C. coronatus) are the causal agents of rhino-facial conidiobolomycosis, a limited soft tissue infection, which is essentially observed in immunocompetent individuals from tropical areas. Rare cases of invasive conidiobolomycosis due to C. coronatus or other species (C.incongruus, C.lamprauges) have been reported in immunocompromised patients. We report here the first case of invasive pulmonary fungal infection due to Conidiobolus pachyzygosporus in a Swiss patient with onco-haematologic malignancy. CASE PRESENTATION: A 71 year-old female was admitted in a Swiss hospital for induction chemotherapy of acute myeloid leukemia. A chest CT performed during the neutropenic phase identified three well-circumscribed lung lesions consistent with invasive fungal infection, along with a positive 1,3-beta-d-glucan assay in serum. A transbronchial biopsy of the lung lesions revealed large occasionally septate hyphae. A Conidiobolus spp. was detected by direct 18S rDNA in the tissue biopsy and subsequently identified at species level as C. pachyzygosporus by 28S rDNA sequencing. The infection was cured after isavuconazole therapy, recovery of the immune system and surgical resection of lung lesions. CONCLUSIONS: This is the first description of C. pachyzygosporus as human pathogen and second case report of invasive conidiobolomycosis from a European country.

Chronic invasive rhinosinusitis by Conidiobolus coronatus, an emerging microorganism.

Fungi from the Conidiobolus genus have been implicated in the development of chronic invasive fungal rhinosinusitis, mainly in tropical countries. The mycosis associated to these fungi may cause irreversible facial deformities and is potentially fatal. The authors present the first case of a chronic invasive fungal rhinosinusitis due to Conidiobolus coronatus diagnosed in a 66-year-old Caucasian male patient, living in Portugal without any travels abroad and complaining of progressive refractory nasal obstruction, facial pain and anosmia. Upon the culture of samples collected during sinus endoscopic surgery, colonies that presented a macroscopic aspect remembering wax were detected. The microscopic evaluation allowed the observation of simple conidiophores forming spherical conidia, and of conidiophores that presented hair-like appendages. Together, these characteristics allowed the identification of the fungi as a Conidiobolus, which was confirmed upon the DNA sequencing. The authors emphasised the role of this fungi as an emergent microorganism as well as the difficulties associated to the diagnosis and treatment.

Rhinofacialentomophthoromycosis.

Entomopthoromycosis is a rare subcutaneous fungal infection caused by onidiobolus coronatus affecting mainly the upper respiratory mucosa in immunocompetent people.The manifestations of this disease masquerades other clinical entities.Hence, high index of suspicion is required for prompt diagnosis.Histopathological examination and culture are the gold standard diagnostic tools, however no standard treatment protocols ha been mentioned in literature.We present a case of rhinofacial entomopthoromycosis in a yearold ma with a leftsided rhinofacial swelling to highlight the presence of this unusual fungal infection and its treatment.

Successful Treatment of Invasive Conidiobolus Infection During Therapy for Acute Lymphoblastic Leukemia.

Invasive fungal infections are a serious cause of morbidity and mortality in patients with hematologic malignancies. Conidiobolus species are molds within the order Entomophthorales and may disseminate to become rapidly fatal in immunocompromised individuals. This species of fungal infections are often multidrug resistant (MDR) and present unique therapeutic challenges. Reports of Conidiobolus infections are rare in pediatric oncology. We report the successful treatment of an adolescent male with B-cell lymphoblastic leukemia and MDR invasive sinopulmonary Conidiobolus infection with emphasis on early and aggressive neutrophil support with surgical debridement. The strategies described could be applied to other MDR fungal infections.

Experimental infection in gerbils by Conidiobolus lamprauges.

Conidiobolomycosis is an emerging entomophthoramycosis caused by fungi Conidiobolus spp. Animal models are essential for the study of infectious disease in various areas such as pathogenesis, diagnostic methods, treatment and prevention. There is not currently an animal model for conidiobolomycosis. The aim of this study was to create an experimental infection protocol for Conidiobolus lamprauges in gerbils (Meriones unguiculatus). The study animals were randomly divided into four groups of four animals: immunosuppressed with cyclophosphamide (CPA) and infected with C. lamprauges (G1), immunocompetent and infected with C. lamprauges (G2), immunosuppressed with CPA (G3), and an immunocompetent control group (G4). Clinical signs were observed only in G1 animals, where the mortality rate reached 75% by day 7 after infection (AI) with a median survival of 2 days. C. lamprauges was detected only in G1, both by PCR and by isolation. Necropsies of the G1 animals showed lesions in the nasal cavity and lung tissue. These lesions were characterized by polymorphonuclear infiltrate cells and by the presence of hyphal structures under silver staining. This animal model will be useful for further investigation of diseases caused by C. lamprauges, particularly of those associated with immunosuppression factors in naturally occurring animal infections.

[A case of rhinofacial entomophthoromycosis in Soudano-Sahelian tropical climate in Burkina Faso]. / Un cas d'entomophthoromycose rhinofaciale en climat tropical soudano-sahélien au Burkina Faso.

We describe a rhinofacial entomophthoramycosis case in a sexagenarian (65 years old) housewife. She was immunocompetent and resident of Burkina Faso. She consulted both the service of dermatology and the service of stomatology of the Teaching Hospital of Bobo-Dioulasso in February 2016 for a diffuse facial tumefaction evolving over six months. This tumefaction was associated with headaches and a left nasal obstruction. Histological examination of the lesion showed an important and polymorphic inflammatory reaction. Also, a filamentous fungus with wide non-septated hyphae and right-angled fungal branching, consistent with mucormycosis was isolated. Mycological diagnosis based on fungal culture with Sabouraud medium without any antibiotic and cyclohexemide after incubation at 27°C and at 30°C was negative. Furthermore, it was not possible to amplify the DNA extracted from biopsy. Antifungal therapy based on the administration of fluconazole per os at 800mg/day was started allowing clinical improvement. This is the first case of a rhinofacial entomophtharomycosis documented in Bobo-Dioulasso. Rhinofacial entomophthoromycosis is largely unknown, even in tropical regions such as Burkina Faso. This lack of knowledge results in a delay in the diagnosis, and subsequently a bad prognosis. It is therefore urgent to improve knowledge on this disease to guide diagnostic steps, prognosis of outcome, and antifungal therapy.

Conidiobolus coronatus granuloma of the right inferior turbinate: A rare presentation.

Fungal infections are common in tropical countries such as India. Very few clinical cases caused by the Entomophthorales Zygomycetes have been reported. Rhinofacial infection is a rare form of zygomycosis in humans, and only limited information regarding optimal treatment is available. We report here a rare case of rhinofacial Conidiobolus coronatus infection in a previously healthy 18-year-old man who presented with a fungal granuloma of the right inferior turbinate and face. Diagnosis was confirmed by microbiologic culture from a tissue biopsy. The infection was successfully treated with surgery and itraconazole therapy for 12 months. The clinical presentation and treatment of this rare, chronic, indolent form of fungal infection are highlighted in this article.

[Conidiobolus coronatus infections revealed by a facial tumor]. / Infection à Conidiobolus coronatus révélée par une tumeur de la face.

INTRODUCTION: Conidiobolomycoses (Conidiobolus coronatus fungal infections) are rare and potentially severe infections prevalent in the tropics. The disease starts in the facial sinus and evolves as a subcutaneous tumor on the mid face OBSERVATION: A 19-year-old female patient from Burkina Faso presented with an acquired nasal deformation having evolved for a few months, associated to bilateral nasal obstruction. The patient had no medical or surgical history. The pathological analysis of the surgical exeresis allowed diagnosing a C. coronatus infection. DISCUSSION: The C. coronatus lives in decaying vegetation in hot and humid climates. It is a potential human pathogen that infects immunocompetent patients presenting with micro-wounds of the sinus and nasal mucosa. Hundred cases have been reported. The management is specific. The diagnosis should be discussed in case of distorting tumors of the midface.

[Rhinofacial conidiobolomycosis associated with cervical, thoracic and brachial localizations: one clinical case in Nigeria]. / Conidiobolomycose rhinofaciale avec localisations cervicales, thoraciques et brachiales: à propos d'un cas nigérian.

We report here the clinical case of a Nigerian adult patient who received medical care during October 2010, at the Center for Diagnosis and Treatment of Buruli ulcer in Pobè (Benin). He presented a massive facial tumor associated with several subcutaneous (cervical, thoracic and upper limbs) nodules, evolving since several years. Tissue samples collected at Pobè medical center were addressed to the mycology and histology laboratories of Angers University Hospital (France), according to the medical exchange agreement between the two institutions about the diagnosis and treatment of Buruli ulcer disease. Histological examination showed a Splendore-Hoeppli phenomenon, consisting of a granulomatous reaction made of eosinophilic polynuclear cells surrounding rare, large and irregular, non-septate hyphae. A filamentous fungus was isolated by cultivation of the clinical samples, which was identified as Conidiobolus coronatus. The patient was treated orally with daily doses of ketoconazole (400 mg per day). After 4 months of treatment, a marked regression of the facial lesion was obtained. A first constructive facial surgery was achieved, but the patient did not attend the second step. This case report allows us to remind the mycological diagnosis of this exotic mycosis, but also to emphasize the main difficulties encountered in medical management in the developing countries.

Development and application of polymerase chain reaction test for detection of Conidiobolus lamprauges / Desenvolvimento e aplicação da reação em cadeia da polimerase para detecção de Conidiobolus lamprauges

Conidiobolomycosis is a granulomatous disease caused by the fungus Conidiobolus spp. in humans and animals. Traditional technique for diagnosis of the disease is isolation of the agent associated with the presence of typical clinical signs and pathological conditions. The aim of this study was to describe the development of a specific polymerase chain reaction (PCR) test for Conidiobolus lamprauges to detect the fungus in clinical samples. Samples from suspected animals were collected and submitted to isolation, histopathological analysis and amplification by PCR. DNA from tissues was subjected to PCR with fungi universal primers 18S rDNA gene, and specific primers were designed based on the same gene in C. lamprauges that generated products of about 540 bp and 222 bp respectively. The culture was positive in 26.6% of clinical samples. The PCR technique for C. lamprauges showed amplification of DNA from fresh tissues (80%) and paraffin sections (44.4%). In conclusion, the PCR technique described here demonstrated a high sensitivity and specificity for detection of fungal DNA in tissue samples, providing a tool for the rapid diagnosis of C. lamprauges.

A conidiobolomicose é uma doença granulomatosa causada pelo fungo Conidiobolus spp., observada em humanos e animais. As técnicas tradicionais de diagnóstico da doença são o isolamento do agente associado à presença de sinais clínicos típicos e condições patológicas. O objetivo deste trabalho é descrever o desenvolvimento de um teste da reação em cadeia da polimerase (PCR) específico para Conidiobolus lamprauges em amostras clínicas. As amostras de animais suspeitos foram coletadas e submetidas ao isolamento, análise histopatológica e amplificação pela PCR. O DNA de tecidos foi submetido a PCR com os iniciadores universais de fungos baseados no gene 18S rDNA e iniciadores específicos foram concebidos com base no mesmo gene em C. lamprauges que gerou produtos de aproximadamente 540 pb e 222 pb, respectivamente. A cultura foi positiva em 26,6% das amostras clínicas. A técnica de PCR para C. lamprauges mostrou a amplificação de DNA a partir de tecidos frescos (80%) e secções de parafina (44,4%). Em conclusão, a técnica de PCR aqui descrita demonstrou elevada sensibilidade e especificidade na detecção de DNA de fungos em amostras de tecido, proporcionando uma ferramenta rápida para o diagnóstico de C. lamprauges.

In vitro susceptibility of Conidiobolus lamprauges recovered from sheep to antifungal agents.

Data regarding the susceptibility of Conidiobolus lamprauges is limited and there is no consensus about the optimal treatment for infections caused by Conidiobolus spp. In this context, the objective of this study was to evaluate the in vitro susceptibility of six C. lamprauges strains isolated from sheep conidiobolomycosis to amphotericin B, ketoconazole, fluconazole, itraconazole, posaconazole, voriconazole, anidulafungin, caspofungin, micafungin, flucytosine, and terbinafine using the CLSI M38-A2 microdilution technique. Terbinafine was the most active (MIC range <0.06-0.5 µg/mL). Resistance or reduced susceptibility was observed for amphotericin B and azole and echinocandin antifungals. Additional studies are necessary to determine the therapeutic potential of terbinafine as monotherapy or in combination therapy with other antifungals.