Navigating treatment for basidiobolomycosis: a qualitative review of 24 cases.

BACKGROUND AND OBJECTIVES: Zygomycosis, a severe form of fungal infection, is classified into two categories: Mucorales and Entomophthorales. Within the Entomophthorales category, Basidiobolomycosis is a rarely recognized genus that can have significant health implications. Prompt diagnosis and appropriate treatment, which includes the use of antifungal medication and surgical procedures, are vital for enhancing the prognosis of patients. The objective of this study is to investigate the response to treatment in patients hospitalized due to basidiobolomycosis. METHODS: We carried out a retrospective study, in which we analyzed data from 49 patients who were diagnosed with Entomophthorale, Zygomycosis, and Basidiobolomycosis at Namazi Hospital, Shiraz, between the years 1997 and 2019. The data included parameters such as demographic information, clinical symptoms, imaging findings, treatment methods, and patient outcomes. RESULTS: Out of 49 patients, 24 children, predominantly male (83.3%), were definitively diagnosed with basidiobolomycosis. The ages of the patients ranged from 1 to 16 years, with an average of 5.75 years. The most frequently observed clinical manifestations included abdominal pain (70.8%), fever (54.2%), hematochezia (41.7%), vomiting (20.8%), and anorexia (16.7%). Half of the patients exhibited failure to thrive (FTT), while abdominal distension was present in 25% of the cases, and a palpable abdominal mass was found in 37% of the patients. The primary treatment strategy incorporated surgical interventions complemented by a comprehensive antifungal regimen. This regimen included medications such as amphotericin B, cotrimoxazole, itraconazole, potassium iodide, and voriconazole. These were mainly administered in a combination therapy pattern or as a monotherapy of amphotericin B. Twenty-two patients were discharged, while two patients died due to complications from the disease. CONCLUSION: Our findings indicate that the prevailing treatment modalities generally involve surgical intervention supplemented by antifungal regimens, including Amphotericin B, Cotrimoxazole, Potassium Iodide, and Itraconazole.

Entomoftoromicosis por Conidiobolus coronatus en un paciente joven proveniente de área rural / Entomophthoromycosis due to Conidiobolus coronatus in a young patient from a rural area

La conidiobolomicosis es una micosis subcutánea causada por un hongo saprofito, Conidiobulus spp. perteneciente a la clase Zigomicetos, orden Entomoftorales, que habita en regiones tropicales. La manifestación clínica clásica es la deformidad progresiva de estructuras faciales y su diagnóstico se basa en cultivos de la zona afectada y el estudio histopatológico, siendo el "fenómeno de Splendore-Hoeppli" el hallazgo más característico. Dada su baja frecuencia de presentación, no existe consenso sobre la mejor opción y tiempo de tratamiento. Aquí presentamos un caso de entomoftoromicosis rinofacial causada por Conidiobolus coronatus en un paciente inmunocompetente de la región sur de Colombia.

Conidiobolomycosis is a subcutaneous mycosis caused by a saprophytic fungus, Conidiobulus, belonging to the class of Zygomycetes, an order of Entomophtorales that inhabits tropical regions. Its most frequent clinical manifestation is the progressive deformity of facial midline structures, and the diagnosis is based on cultures taken from the affected area and the histopathological study, being the "Splendore-Hoeppli phenomenon" the most characteristic finding. Due to its low frequency of presentation, there is no consensus about the best option and treatment time. We present a case of rhinofacial entomophthoromycosis caused by Conidiobolus coronatus in an immunocompetent patient from the southern region of Colombia.

Subcutaneous zygomycosis in an immunocompetent patient caused by Basidiobolus ranarum.

Zygomycosis is a fungal infection in humans caused by orders Mucorales and Entomophthorales. The incidence of Mucorales causing mucormycosis is on a rise and is well documented, whereas Entomophthorales is rare. Among Entomophthorales, infections caused by Conidiobolus are more common than Basidiobolus Here we present a case of subcutaneous basidiobolomycosis in a female patient. The patient had hyperpigmentation in the thigh region for 6 months and serous discharge for 4 months. All initial findings suggested the inflammatory stage of morphea. Differential diagnoses of granuloma annulare, malignant melanoma and morphea were considered radiologically. A good suspicion of fungal aetiology by the dermatologist led to an appropriate diagnosis of subcutaneous basidiobolomycosis based on fungal culture and histopathological examination. Based on macroscopic and microscopic findings, the causative organism was confirmed to be Basidiobolus ranarum The patient was started on oral potassium iodide and itraconazole and showed a good prognosis.

Rhinofacial conidiobolomycosis: Clinical and microbiological characterisation and shift in the management of a rare disease.

BACKGROUND: Conidiobolomycosis is a rare tropical rhinofacial fungal infection which has not been well characterised. The available evidence in its management is sparse due to lack of clinical studies and the limited data on antifungal susceptibility patterns. OBJECTIVE: To analyse the clinical manifestations, antifungal treatment and outcomes of patients with conidiobolomycosis and to determine antifungal susceptibility profiles of the isolates. PATIENTS/METHODS: Retrospective analysis of data of all patients with a diagnosis of conidiobolomycosis confirmed by histopathology and culture at a tertiary care hospital from 2012 to 2019 was done. RESULTS: There were 22 patients, 21 males and one female, with a mean age of 37.1 years. Most common presenting symptom was nasal obstruction, found in 20 (90.90%) patients. Patients who presented within 12 months had a better cure rate (85%) compared to those who presented late (67%). Among the 19 patients who had a follow-up, good outcome was seen in 15 of the 17 (88.24%) patients who were on itraconazole or potassium iodide containing regimen. Of the six patients who received additional trimethoprim-sulphamethoxazole (co-trimoxazole), 67% showed good outcome with two patients showing complete cure and two patients still on treatment with significant improvement. High minimum inhibitory concentration (MIC) values were noted for azoles and amphotericin B, whereas co-trimoxazole showed lowest MIC ranges. CONCLUSION: Itraconazole and potassium iodide are reasonable first-line options for the treatment of conidiobolomycosis. Good clinical response to KI and comparatively lower MIC of co-trimoxazole are promising. Further studies are required for developing clinical breakpoints that can predict therapeutic outcomes.

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.

Molecular epidemiology of zygomycosis and their related factors in tertiary referral centers in southern Iran.

INTRODUCTION: For the best management of the zygomycosis in immunocompromised patients, the present study aims to detect and identify the etiologic agents by DNA sequencing method and their related factors in clinical samples of patients. METHODOLOGY: Clinical samples from 1,058 patients admitted in 11 university hospitals in Shiraz, Southern Iran were collected between July 2015 and July 2018. All samples (bronchoalveolar lavage, sputum, blood, tissue) were examined by routine microscopic and culture tests for zygomycetes. The etiologic agents were identified by the molecular method and sequencing. RESULTS: Direct microscopic examinations or pathology smear, culture, and PCR were positive in 61 (5.8%), 15 (1.4%), and 103 (9.7%) patients, respectively. According to EORTC/MSG criteria, the rates of proven, probable, and possible zygomycosis were 59.2% (61/103), 14.6% (15/103), and 26.2% (27/103 patients), respectively. The most prevalent etiologic agents according to sequencing were Rhizopus oryzae (44 cases), Rhizopus microsporus (31 cases), Rhizopus stolonifer (15 cases). Twenty-two patients (21.4%) with positive PCR died. There were significant relations between zygomycosis and the underlying disease (p = 0.043) and prior antifungal therapy (p = 0.023). White blood cell count was in the normal range in 14.1% of patients, and the means of erythrocyte sedimentation rate (ESR) and C reactive protein (CRP) were 65 mm/hour and 57 mg/L, respectively. CONCLUSIONS: Molecular methods and sequencing may have considered as suitable tools to diagnose zygomycosis. Identification of the etiologic agents may be considered as the future antifungal therapy and management of the respective patients.

Evolutionary relationships among Massospora spp. (Entomophthorales), obligate pathogens of cicadas.

The fungal genus Massospora (Zoopagomycota: Entomophthorales) includes more than a dozen obligate, sexually transmissible pathogenic species that infect cicadas (Hemiptera) worldwide. At least two species are known to produce psychoactive compounds during infection, which has garnered considerable interest for this enigmatic genus. As with many Entomophthorales, the evolutionary relationships and host associations of Massospora spp. are not well understood. The acquisition of M. diceroproctae from Arizona, M. tettigatis from Chile, and M. platypediae from California and Colorado provided an opportunity to conduct molecular phylogenetic analyses and morphological studies to investigate whether these fungi represent a monophyletic group and delimit species boundaries. In a three-locus phylogenetic analysis including the D1-D2 domains of the nuclear 28S rRNA gene (28S), elongation factor 1 alpha-like (EFL), and beta-tubulin (BTUB), Massospora was resolved in a strongly supported monophyletic group containing four well-supported genealogically exclusive lineages, based on two of three methods of phylogenetic inference. There was incongruence among the single-gene trees: two methods of phylogenetic inference recovered trees with either the same topology as the three-gene concatenated tree (EFL) or a basal polytomy (28S, BTUB). Massospora levispora and M. platypediae isolates formed a single lineage in all analyses and are synonymized here as M. levispora. Massospora diceroproctae was sister to M. cicadina in all three single-gene trees and on an extremely long branch relative to the other Massospora, and even the outgroup taxa, which may reflect an accelerated rate of molecular evolution and/or incomplete taxon sampling. The results of the morphological study presented here indicate that spore measurements may not be phylogenetically or diagnostically informative. Despite recent advances in understanding the ecology of Massospora, much about its host range and diversity remains unexplored. The emerging phylogenetic framework can provide a foundation for exploring coevolutionary relationships with cicada hosts and the evolution of behavior-altering compounds.

Ocular basidiobolomycosis - Rare presentation: A case report.

Basidiobolus ranarum is an uncommon pathogen in ocular infections. It has been previously reported from subcutaneous and gastrointestinal infections. Here, we report a rare case of ocular infection caused by B. ranarum. A 21-year-old male patient presented with visual loss and pain in the right eye due to corneal abscess following an injury while welding. KOH mount performed was indicative of fungal hyphae. Fungal culture revealed growth of B. ranarum. Meanwhile, the patient was treated with antifungal (topical natamycin and oral ketoconazole) along with total corneal transplantation. B. ranarum is a fungus very uncommonly causing ocular pathogenesis. This results in diagnostic confusion leading to poor treatment outcomes. Hence, a mycology laboratory has to be aware about this fungus and need to consider it as a differential diagnosis in patients with infectious corneal abscess.

Basidiobolus haptosporus-like fungus as a causal agent of gastrointestinal basidiobolomycosis.

Basidiobolus species were isolated from colonic biopsy samples of patients with gastrointestinal basidiobolomycosis (GIB) in southern Saudi Arabia. Isolated fungi were initially identified using classical mycological tools and confirmed by sequence analysis of the large subunit ribosomal RNA gene. Phenotypic tests revealed zygomycete-like fungi which conform to those of Basidiobolus species. Five sequenced strains formed a monophyletic clade in the 28S ribosomal RNA gene phylogenetic tree. They shared 99.97% similarity with B. haptosporus and 99.97% with B. haptosporus var. minor, and relatively lower similarity with B. ranarum (99.925%). The study suggests a new and a serious causal agent of GIB related to Basidiobolus haptosporus. These isolates are not related to B. ranarum, which is commonly linked to this disease.

Antifungals in a case of basidiobolomycosis: role and limitations.

A 10-year-old Saudi boy was diagnosed to have basidiobolomycosis after a stormy course of his ailment. Therapy was initiated with intravenous antifungal, voriconazole, which was well tolerated for 6 weeks except for local excoriation at the site of ileostomy. He developed drug-induced hepatitis on oral voriconazole, therefore, switched to oral itraconazole following which he experienced severe chest pain. Alternatively, co-trimoxazole (bactrim) an antibacterial with antifungal activity was prescribed but he had the intolerance to it as well. Unfortunately, posaconazole as an alternative antifungal was not available in our centre. We report here a Saudi boy who developed an intolerance to most common antifungals used clinically 6 weeks after the therapy was initiated.

Diet influences the bacterial and free fatty acid profiles of the cuticle of Galleria mellonella larvae.

The evolutionary success of insects is arguably due to their ability to build up a complex, highly-adaptable and very effective defense system against numerous pathogens, including entomopathogenic fungi. This system relies on the humoral immune system and cellular defense reactions. The first line of defense against biological pathogens is a cuticle formed of several layers. The cuticular lipids may contain hydrocarbons, free fatty acids (FFA), alcohols, waxes, glycerides, aldehydes and sterols. Cuticular fatty acids may also play a role in defending against fungal invasion. Our present findings show that the diet of insects can have a significant effect on their sensitivity and defense response to pathogens; for example, while G. mellonella larvae fed on beeswax had a similar appearance to those reared on a semi-artificial diet, they possessed a different cuticular free fatty acid (FFA) profile to those fed on a semi-artificial diet, and were less sensitive to Conidiobolus coronatus infection. It is possible that the presence of heneicosenoic acid (C21:1) and other long-chain free fatty acids (C22:0, C24:0, C26:0), as well as Brevibacillus laterosporus bacteria, on the cuticle of larvae fed on beeswax, plays a protective role against fungal invasion. Insect pests represent a global problem. An understanding of the basic mechanisms underlying the fungal infection of insects might provide a clearer insight into their defenses, thus allowing the design of more effective, and environmentally-friendly, means of controlling them. The greater wax moth is an excellent model for the study of immunology resistance. Knowledge of the influence of diet on pathogen resistance in insects can be also useful for creating a model of human diseases caused by pathogens, such as Candia albicans.

Gastrointestinal basidiobolomycosis: An emerging mycosis difficult to diagnose but curable. Case report and review of the literature.

BACKGROUND: Gastrointestinal basidiobolomycosis (GIB) is a rare mycosis affecting almost exclusively immunocompetent subjects. METHODS: We describe a case of GIB caused by Basidiobolus ranarum in a 25-year-old Italian immunocompetent man resident in Ireland who presented a 2-month history of epigastric pain. Suspecting colon cancer he underwent a right hemicolectomy subsequently leading to a diagnosis of GIB by means of molecular biology. After surgery a 9-month therapy with itraconazole was employed with a good outcome. A review of medical literature regarding GIB cases published in the period 1964-2017 is presented. RESULTS: One-hundred and two cases of GIB were included in this analysis. The disease was observed predominantly in male gender (74.5%) and children (41.2%). Abdominal pain was the single most common complaint (86.3%) followed by fever (40.2%) and evidence of an abdominal mass (30.4%). Peripheral blood eosinophilia was detected in 85.7% of cases. Most of the patients were diagnosed in Saudi Arabia (37.2%) followed by USA (21.6%) and Iran (20.6%). Surgery plus antifungal therapy was employed in the majority of patients (77.5%). An unfavourable outcome was documented globally in 18.6% of patients. CONCLUSIONS: GIB seems to be an emerging intestinal mycosis among immunocompetent patients living in the Middle East and Arizona.

Rhinocerebral Zygomycosis Due to a Lichtheimia ramosa Infection in a Calf: Neural Spread Through the Olfactory Nerves.

Here, we report a case of rhinocerebral zygomycosis due to a Lichtheimia ramosa infection in a calf. A histopathological examination revealed that a fungus had invaded the brain through the olfactory nerves. Lichtheimia ramosa was detected by polymerase chain reaction analysis of DNA extracted from formalin-fixed paraffin-embedded samples of the affected tissue. This is the first case of rhinocerebral zygomycosis to involve cattle. Also, this is the first such case to involve fungal invasion into the central nervous system through the cranial nerve itself, rather than through perineural tissue.

A first-line antiretroviral therapy-resistant HIV patient with rhinoentomophthoromycosis.

The Conidiobolus coronatus-related rhinoentomophthoromycosis in immunocompetent and immunocompromised (HIV negative) individuals has been treated successfully with antifungal drugs. However, C. coronatus infections in first-line antiretroviral therapy (ART)-resistant (HIV infected) individuals particularly with rhinoentomophthoromycosis have not been reported previously. Here, we describe a case of itraconazole non-responding rhinoentomophthoromycosis in an HIV-infected patient with first-line antiretroviral (ART) drug resistance which was successfully managed through systematic diagnostic and therapeutic approaches in dermatologic setting. A 32-year-old HIV-1-infected man presented with painless swelling, nasal redness and respiratory difficulty. The patient was receiving first-line ART and had a history of traumatic injury before the onset of nasopharyngeal manifestations. The patient's previous history included oral candidiasis and pulmonary tuberculosis.

Basidiobolomycosis complicated by hydronephrosis and a perinephric abscess presenting as a hypertensive emergency in a 7-year-old boy.

A 7-year-old boy presented with a chronic, indurated, tender left thigh swelling in association with a hypertensive emergency. He had a bilateral moderate degree of hydronephrosis and a left perinephric abscess, and MRI features of posterior reversible encephalopathy syndrome. Histopathological examination of the biopsy specimen demonstrated eosinophilic fasciitis with filamentous fungi. Basidiobolus ranarum was isolated from the culture. The fungus was also isolated from a perinephric fluid aspirate. Computerised tomography of the abdomen demonstrated features consistent with fungal invasion of the pelvic floor muscles and urinary bladder, leading to bilateral hydronephrosis. He required multiple antihypertensive drug therapy and was treated with intravenous amphotericin B, oral itraconazole and potassium iodide. Antihypertensive agents were discontinued after 2 weeks of antifungal therapy. At 6-months follow-up, the hydronephrosis had resolved completely. Perinephric abscess associated with basidiobolomycosis has not been reported previously.

Gastro-intestinal basidiobolomycosis in a 2-year-old boy: dramatic response to potassium iodide.

Gastro-intestinal basidiobolomycosis (GIB) is a rare fungal infection caused by Basidiobolus ranarum. Treatment includes surgical resection and long-term antifungal therapy. A 2.5-year-old boy presented with a 10-day history of abdominal pain, fever and diarrhoea, and a palpable abdominal mass was detected. Resection was undertaken and histology confirmed basidiobolomycosis. Treatment with amphotericin B and itraconazole was commenced, but the infection progressed and spread to involve the intestines, liver, ribs and lung, and also the abdominal wall after 6 months, requiring four operative procedures. Because of unresponsiveness to amphotericin and itraconazole, oral potassium iodide was added which resulted in complete resolution of the infection. Potassium iodide is an essential component of the treatment of systemic B. ranarum.

Epidemiology of Zygomycosis: Analysis of National Data from Pathological Autopsy Cases in Japan.

BACKGROUND AND METHODS: To identify recent trends in the frequency of zygomycosis in autopsy cases, we conducted epidemiological analysis every four years from 1989 to 2009 using national data reported in the "Annual of Pathological Autopsy Cases in Japan." RESULTS: 153,615 cases were autopsied, of which 6622 (4.3%) were found to have had mycosis. Among these, there were 243 cases (3.7%) of zygomycosis, which was the fourth most predominant causative agent of mycoses among the monopathogen mycoses. Of the complicated mycoses, zygomycosis accounted for 56 cases. A total of 299 cases with zygomycoses were observed. The frequency of zygomycosis appeared to be generally stable over the twenty-year period from 1989 to 2009, at around 4% of autopsy cases having mycosis. Younger patients tended to have severe and complicated infections that were characteristic of zygomycosis, compared with non-zygomycosis. The pulmonary and gastrointestinal (GI) systems were the most common foci in our analysis, reflecting the severity of zygomycosis in these sites. Hematological disease was the most frequent underlying disease, but there was a peak of neonatal infections in 2009, which was the first time that this was observed in our studies. CONCLUSION: These results of the epidemiological analysis of autopsy cases with mycosis demonstrate that clinicians should promptly recognize and treat zygomycosis.