Chronic Fungal Infection Research Articles

Epidemiological and clinical aspects of sporotrichosis in patients seen at a reference hospital in Madagascar.

Sporotrichosis is a subacute to chronic fungal infection of skin and subcutaneous tissues, caused by dimorphic fungi belonging to the genus Sporothrix, commonly seen in tropical and subtropical regions like Madagascar. This study describes the epidemiological, clinical, and the treatment outcomes with itraconazole for sporotrichosis. A descriptive retrospective study on patients suffering from sporotrichosis, from March 2013 to January 2019, was conducted, in the reference center for endemic mycoses. Patients with sporotrichosis who received itraconazole for at least 3 months were included in the study. Patients received itraconazole 200 mg daily for 3 to 6 months. Therapeutic responses were evaluated at months 3 and 6 after treatment. Outcomes were classified as minor response, major response, cure, and failure. Forty-three cases of sporotrichosis were included. The median age of patients was 40 years. Most of them (62.8%) were rural workers. Men were more frequently infected (72%). At the end of 6th month of treatment, 20 patients (46.5%) were cured and a major response to itraconazole was observed in 8 patients (18.6%). The cure rate was higher in 12 patients (27.9%) who had disease durations of less than to one year than in those who had more time of disease (18.6%) (p = 0.01). Thirteen patients (30.2%) were lost to follow up. The rate of lost to follow-up was also higher (39.5%) in patients who had sporotrichosis of less than to one year than in those who had more time of disease. The cure rate found in this study was inferior to that reported in the literature. However, it was higher in patients with early symptomatology.

ORCHITIS and Chronic Granulomatous Disease

Chronic Granulomatous Disease (CGD) is a primary immunodeficiency disorder, which is almost always characterized by impairment of the function of leukocytes and generally presents with recurrent chronic relapsing bacterial or fungal infection. This study reported a three-year-old boy who was referred to the Pediatric Hematology and Oncology Center of Shohada Khalij-e-Fars general hospital, Bushehr with recurrent lymphadenitis, and orchitis, who suffered from this disease. Since confirmation of diagnosis, he is receiving Co-trimoxazole three times per week as prophylaxis, and the plan for him is hematopoietic stem cell transplantation (HSCT).

A Novel Interleukin 17 Receptor A Mutation in a Child with Chronic Mucocutaneous Candidiasis and Staphylococcal Skin Infections.

Chronic mucocutaneous candidiasis leads to persistent or recurrent fungal infections of the nail, skin, oral, and genital mucosa. Impaired interleukin 17-mediated immunity is a cause of chronic mucocutaneous candidiasis. We aimed to show the pathogenicity of a novel interleukin 17 receptor A mutation through functional studies. After next-generation sequencing analysis showed the interleukin 17 receptor A variant, we confirmed the variant by Sanger sequencing and functional validation of the variant by flow cytometry. We present the case of a 6-year-old male patient who presented with recurrent oral and genital Candida infections and eczema. He had staphylococcal skin lesions, fungal susceptibility, and eczema. The patient carried a novel homozygous nonsense [(c.787C> T) (p.Arg263Ter)] mutation in the interleukin 17 receptor A gene. Sanger sequencing confirmed the variant and revealed the segregation of the variant in the family. We used flow cytometry to detect interleukin 17 receptor A protein expression in peripheral blood mononuclear cells from patients and measured Th17 cell percentage. We observed low interleukin 17 receptor A protein expression in patient peripheral blood mononuclear cells, decreased CD4+ interleukin 17+ cell percentage, and decreased interleukin 17F expression in CD4+ cells compared to healthy controls. Innate immune defects may lead to chronic recurrent fungal and bacterial infections of the skin, mucosa, and nails. Generally, genetic and functional analysis is needed in addition to basic immunological tests.

In host evolution of Exophiala dermatitidis in cystic fibrosis lung micro-environment.

Individuals with cystic fibrosis (CF) are susceptible to chronic lung infections that lead to inflammation and irreversible lung damage. While most respiratory infections that occur in CF are caused by bacteria, some are dominated by fungi such as the slow-growing black yeast Exophiala dermatitidis. Here, we analyze isolates of E. dermatitidis cultured from two samples, collected from a single subject 2 years apart. One isolate genome was sequenced using long-read Nanopore technology as an in-population reference to use in comparative single nucleotide polymorphism and insertion-deletion variant analyses of 23 isolates. We then used population genomics and phylo-genomics to compare the isolates to each other as well as the reference genome strain E. dermatitidis NIH/UT8656. Within the CF lung population, three E. dermatitidis clades were detected, each with varying mutation rates. Overall, the isolates were highly similar suggesting that they were recently diverged. All isolates were MAT 1-1, which was consistent with their high relatedness and the absence of evidence for mating or recombination between isolates. Phylogenetic analysis grouped sets of isolates into clades that contained isolates from both early and late time points indicating there are multiple persistent lineages. Functional assessment of variants unique to each clade identified alleles in genes that encode transporters, cytochrome P450 oxidoreductases, iron acquisition, and DNA repair processes. Consistent with the genomic heterogeneity, isolates showed some stable phenotype heterogeneity in melanin production, subtle differences in antifungal minimum inhibitory concentrations, and growth on different substrates. The persistent population heterogeneity identified in lung-derived isolates is an important factor to consider in the study of chronic fungal infections, and the analysis of changes in fungal pathogens over time may provide important insights into the physiology of black yeasts and other slow-growing fungi in vivo.

Magnitude and associated factors of Pityriasis Versicolor among patients attending Dermatovenereology Outpatient Department at the University of Gondar Comprehensive Specialized Hospital, Northwest Ethiopia

Pityriasis versicolor (PV) is a chronic superficial fungal infection caused by Malassezia species. It is the most common dermatologic disorder in tropical countries including Ethiopia and skin discoloration is the principal morbidity resulting from pityriasis versicolor. Therefore, this study assess the prevalence and associated factors of PV among patients attending Dermatovenereology clinic at the University of Gondar Comprehensive Specialized Hospital. Hospital based cross sectional study design was employed. Systematic random sampling was used and a total of 406 participants who attended Dermatovenereology OPD were included in the study. Data were collected by interview and physical examination. Then it was checked, coded, entered into Epi-Info version 7 and analyzed using Stata version 14. Both bivariable and multivariable logistic regression were employed to identify factors associated with PV. Adjusted odds ratio with their corresponding 95% CI and P-value were calculated. A P-value less than 0.05 was used to declare statistically significant variables. The overall magnitude of PV among patients attending Dermatovenereology OPD at the UGCSH was 12.6% (95%CI; 9.2%, 15.0%).Those who had a diploma and above education [AOR: 95% CI; 4.67 (1.18, 18.47)], excessive sweating [AOR: 95% CI; 4.75 ( 1.92, 8.76)] being male [AOR: 95%CI; 4.19 (1.92, 9.14)], practicing regular exercise [AOR: 95% CI; 4.11 (1.93, 8.76)] and wearing heavy clothes [AOR: 95% CI; 2.53 (1.24, 5.15)] were found to be statistically significantly associated with PV. This study found that the magnitude of Pityriasis versicolor was relatively lower. The study revealed that educational status (diploma and above), male gender, habit of regular exercise, excessive sweating and wearing heavy cloths were significantly associated with Pityriasis Versicolor. It is recommended that high risk patients receive close follow up and health professionals should provide health education sessions in waiting rooms about the identified risk factors.

Case of Mixed Infection of Toenail Caused by Candida parapsilosis and Exophiala dermatitidis and In Vitro Effectiveness of Propolis Extract on Mixed Biofilm

Onychomycosis is a chronic fungal nail infection caused by several filamentous and yeast-like fungi, such as the genus Candida spp., of great clinical importance. Black yeasts, such as Exophiala dermatitidis, a closely related Candida spp. species, also act as opportunistic pathogens. Fungi infectious diseases are affected by organisms organized in biofilm in onychomycosis, making treatment even more difficult. This study aimed to evaluate the in vitro susceptibility profile to propolis extract and the ability to form a simple and mixed biofilm of two yeasts isolated from the same onychomycosis infection. The yeasts isolated from a patient with onychomycosis were identified as Candida parapsilosis sensu stricto and Exophiala dermatitidis. Both yeasts were able to form simple and mixed (in combination) biofilms. Notably, C. parapsilosis prevailed when presented in combination. The susceptibility profile of propolis extract showed action against E. dermatitidis and C. parapsilosis in planktonic form, but when the yeasts were in mixed biofilm, we only observed action against E. dermatitidis, until total eradication.

Onychomycosis: Old and New.

Onychomycosis is a common chronic fungal infection of the nail that causes discoloration and/or thickening of the nail plate. Oral agents are generally preferred, except in the case of mild toenail infection limited to the distal nail plate. Terbinafine and itraconazole are the only approved oral therapies, and fluconazole is commonly utilized off-label. Cure rates with these therapies are limited, and resistance to terbinafine is starting to develop worldwide. In this review, we aim to review current oral treatment options for onychomycosis, as well as novel oral drugs that may have promising results in the treatment of onychomycosis.

A Rare Case of Extensive Chromoblastomycosis

Chromoblastomycosis also known as chromomycosis is a chronic fungal infection of the skin and subcutaneous tissue. The infection usually results from traumatic injury or inoculation of microorganism from a specific group of dematiaceous fungi.

Onychomycosis due to Trichophyton violaceum in HIV/AIDS patients of sub-Saharan Africa

High prevalence of HIV/AIDS in sub-Saharan Africa is responsible for very high burden of mycotic infections. Also, most of the countries here have highly burdened health system compared to their health budget. Onychomycosis is a chronic fungal infection of fingers and toenails. It is usually caused by dermatophytes, yeasts, and non-dermatophyte molds (NDM). Prevalence and severity of infection is more in immunosuppressed individuals, especially with HIV/AIDS. The laboratory diagnosis of the causative organism is very important to initiate the specific treatment. Persistence of infection can be the source of infection to the patient himself by autoinoculation and to others. The treatment of HIV/AIDS is mandatory. Onychomycosis in HIV/AIDS patients is usually due to Trichophyton rubrum and involve the toenails. The reports of onychomycosis due to dermatophytes from sub-Saharan Africa are scanty. There are only two reports, which have mentioned onychomycosis due to (T.violaceum) and involvement of fingernails in HIV/AIDS.

Antibodies against Histoplasma capsulatum and Aspergillus fumigatus among chronic TB patients in Indonesia: a cross-sectional study.

Chronic pulmonary fungal infections may occur in patients with previous history of pulmonary tuberculosis (TB), and are often clinically misclassified as TB, especially when bacteriological confirmation for Mycobacterium tuberculosis is absent. In this study, we investigated the prevalence of antibody against Histoplasma capsulatum and Aspergillus fumigatus in patients with confirmed and clinically chronic TB. Antibodies against H. capsulatum and A. fumigatus were measured from serum samples using enzyme-linked immunosorbent assay (ELISA). The presence M. tuberculosis in sputum was confirmed using smear microscopy, GeneXpert MTB/RIF assay, or culture. Antibodies against H. capsulatum and A. fumigatus were elevated in 16.9% and 26.9% of bacteriologically confirmed chronic TB patients, and 12.1% and 18.2% in those without bacteriological confirmation, respectively. Approximately one-third of patients who had positive anti-Histoplasma antibody also had elevated levels of antibody against Aspergillus fumigatus (P<.001). Our study highlights the importance of chronic pulmonary fungal infection in post-TB patients with recurrent respiratory symptoms.

PREVALENCE OF (Aspergillus niger) IN OTOMYCOSIS AT PROF. DR. MARGONO SOEKARJO HOSPITAL

Otomycosis is a chronic fungal infection with high prevalence. Environmental factors dan predisposing factors can influence a patient’s vulnerability to otomycosis. According to studies conducted in several country, Aspergillus niger is the common fungus that causes otomycosis. This study aims to determine the prevalence of Aspergillus niger in patients at Prof. dr. Margono Soekarjo Hospital, who was clinically diagnosed with otomycosis. The study was done at the ENT Poly of Prof. dr. Margono Soekarjo Hospital and Microbiology Laboratory of Medicine Faculty, Jenderal Soedirman University between August 2022 to Januari 2023 as a descriptive observational study. According to the inclusion criteria, there were 42 subjects and 46 samples that ENT specialists carried out with sterile flocked swabs, the isolated the samples bedside on SDA Chloramphenicol, Czapek Dox agar, and object glass. Samples were observed macroscopically and microscopically with 10% KOH and LPCB staining. Patients with Aspergillus niger infection in otomycosis at Prof. dr. Margono Soekarjo Hospital , are represented by nine (19,56%) out of the 46 samples. The gender with the highest sex precentage is female (55,56%), folllowed by the age range of 26 – 35 years (44,45%). The prevalence of Aspergillus niger as a cause of otomycosis in Prof. dr. Margono Soekarjo Hospital is 19,56%, the most in females and the age group 26 – 35 years.&#x0D;

Comparison of diagnostic methods in onychomycosis

Aim: Onychomycosis is a chronic fungal infection of the nail bed, plate, or matrix. This study aimed to compare the sensitivity of three diagnostic methods in the diagnosis of onychomycosis.&#x0D; Material and Method: This study included 39 patients with a clinical diagnosis of onychomycosis of the toenails, who presented to Medipol Mega University Hospital between May 2019 and August 2022. Using the nail samples taken from the patients, the results of the direct microscopic examination with standard potassium hydroxide (KOH), histopathological examination performed with periodic acid-Schiff (PAS) staining, and fungal agents that grew in fungal culture were noted.&#x0D; Results: Eleven (28.2%) patients were female, and 28 (71.8%) were male, with the mean age being 43.1±13.9 years. Of the patients, 53.8% had distal subungual onychomycosis and 46.2% had total subungual onychomycosis. The mean disease duration was 38.8±24.5 (12-120) months. Fungal infection was detected on direct microscopic examination with standard KOH in 66.7% of the patients, culture growth in 38.5%, and PAS staining on histopathological examination in 71.8%, and the sensitivities of these methods were determined as 74.3%, 49.2%, and 80%, respectively, with the negative predictive values being 30.8%, 16.7%, and 36.4%, respectively.&#x0D; Conclusion: Among the investigated methods, histopathological examination with PAS staining was found to have the highest sensitivity and negative predictive value in the diagnosis of onychomycosis.

Chromoblastomycosis Treated With Posaconazole and Adjunctive Imiquimod: Lending Innate Immunity a Helping Hand.

Chromoblastomycosis (CBM) is a difficult-to-treat, chronic fungal infection of the skin and subcutaneous tissue. The evidence base for treatment is scarce, with no standardized therapeutic approach. Chronicity of CBM infection is postulated to be due in part to a failure of host cell-mediated immunity to generate a proinflammatory response sufficient for fungal clearance. We present a case of a chronic chromoblastomycosis lesion of the hand present for nearly 4 decades, previously refractory to itraconazole monotherapy, that was successfully treated with a combination of posaconazole and adjunctive immunotherapy with topical imiquimod, a Toll-like receptor 7 agonist. Serial biopsies and images demonstrate the clinical and histopathological improvement of the lesion. Randomized trials of antifungal therapy with adjunctive imiquimod are warranted to determine whether a combination of antifungal and host-directed therapy improves outcomes for this neglected tropical mycosis.

Using a Madurella mycetomatis-specific PCR on grains obtained via non-invasive fine-needle aspirated material is more accurate than cytology.

Eumycetoma is a chronic subcutaneous inflammatory fungal infection most often caused by the fungus Madurella mycetomatis. Using a species-specific PCR on DNA directly isolated from grains is currently the most reliable method for species identification. However, so far, PCR has been performed on grains obtained through deep-seated surgical biopsies, which are invasive procedures. Grains can also be obtained via ultrasound-guided fine-needle aspiration (US-FNA). Here we determined the diagnostic performance of species-specific PCRs performed on samples obtained through US-FNA. From 63 patients, US-FNA was performed to obtain eumycetoma grains; 34 patients also underwent a deep-seated biopsy. From the grains, DNA was isolated, and one pan-fungal and two M. mycetomatis-specific PCRs were performed. The sensitivity and specificity were determined. Of the 63 patients who underwent US-FNA, 78% (49/63) had evidence of eumycetoma based on cytology and 93.7% (59/63) based on species-specific PCRs. In the 34 patients for whom surgical biopsies were performed as well, 31 patients had a positive PCR for M. mycetomatis when DNA was isolated from the deep-seated biopsy, and 30 had a positive PCR when DNA was obtained from the US-FNA material. This resulted in a 96.8% sensitivity, and 100% specificity with 97.1% diagnostic accuracy for PCR performed on US-FNA. PCR performed on the US-FNA material has a similar sensitivity and specificity as PCR performed on deep-seated biopsies. Therefore, when using PCR, a deep-seated biopsy may not be necessary to obtain grains.

Sporotrichosis in a Renal Transplant Patient: A Rare Case Report with a Review of the Literature

Sporotrichosis is a rare form of subacute and chronic fungal infection in renal transplant recipients caused by the ubiquitous fungus Sporothrix schenckii. It is usually described in renal allograft recipients who have not been treated with antifungal prophylaxis. We report a rare case of cutaneous sporotrichosis in a 39-year-old renal allograft recipient already on antifungal prophylaxis, who presented with skin lesions. The diagnosis was made from a skin biopsy. The patient had increased tacrolimus levels after starting treatment with itraconazole, which was later changed to terbinafine and cryotherapy. The patient responded to treatment with regression of his lesions.

A Case of Fungus Ball in the Nasal Cavity Imitating a Rhinolith

Fungus balls are a chronic and non-invasive fungal infection. Despite being relatively common in the paranasal sinuses, they are rare in the nasal cavity. The etiology of fungus balls in the nasal cavity is unknown. Fungus balls generally develop slowly and asymptomatically. When symptomatic, they can cause symptoms similar to those of chronic sinusitis or intranasal masses, such as nasal obstruction, nasal and postnasal discharge, head and face pain, and smell perception disorders. The preferred treatment of fungus balls in the nasal cavity is functional endoscopic sinus surgery and debridement. This case report describes a 50-year-old woman operated with a preliminary diagnosis of rhinolith but finally diagnosed with fungus ball as a result of histopathological examination.

Urethral rhinosporidiosis: Prolapsing mass from urethra in a Bangladeshi farmer

Rhinosporidiosis is a chronic granulomatous fungal infection caused by Rhinosporidium seeberi. Usual site of infection is the nasal mucosa & nasopharynx. Male urethra is extremely rare site involving this disease. Here we are reporting a rare case where rhinosporidiosis presented as a prolapsing mass from urethra during voiding.

Neurodegenerative Diseases due to Neurotoxins passing through the Nose-to-Brain Pathway

Three neurodegenerative disorders- Alzheimer’s dementia (ALZ), Parkinson’s disease (PD) and amyotrophic lateral sclerosis (ALS)- share a common feature in their pathogenesis: evidence of mitochondrial dysfunction and reactive oxygen stress. Their pathologic classifications are based on the findings at autopsy based on patterns of protein aggregates in neurons and glial cells. This pathology supports the concept that neurotoxins are a major factor in the etiology of these disorders. There is value in exploring the similarities in the pathogenesis of ALS, Parkinson Disease and Alzheimer Dementia based on non-genetic etiologies. The nose to olfactory pathway feeds sensory input from the nasal cavity to the olfactory bulb and the entorhinal lobe. Another component of these pathways involves two branches of the trigeminal nerve with sensory input to the pons and midbrain. A key factor is their capacity to bypass the blood-brain barrier (BBB). The protection of the brain by the BBB diminishes with age and can be lost with damage from insults as with viral infections. The olfactory nerve is the only cranial nerve with direct exposure to the ambient environment and has a high rate of turnover of sensory receptors. The nasal cavity is being studied for drug delivery and can be used to deliver medications into the central nervous system (CNS. The nose-to-brain pathway may represent a critical avenue of exposure to oxidative neurotoxins. Neurotoxic mycotoxins are a major risk to humans. Neurotoxins may be amplified by the nose-to-brain pathway. The pathology shows similarities to prion disease. These neurotoxins are highly fat-soluble and tend to accumulate in mitochondria and synaptic vesicles. Neurotoxins in synaptic vesicles can migrate from neuron to neuron. There is evidence of chronic fungal infections in ALS patients that secret neurotoxic and immunotoxic mycotoxins leading to progressive immune suppression. The nose-to-olfactory pathway may amplify neurotoxins levels in the brain. If Parkinson Disease and ALZ are due to systemic poisonings, the source of neurotoxins may be episodic and lead to autoimmune disease.

NIMG-94. A RARE CASE OF INFRATENTORIAL CEREBELLAR VERMIS MULTINODULAR AND VACUOLATING NEURONAL TUMOR

Abstract INTRODUCTION Multinodular and vacuolating neuronal tumor (MVNT) is a rare entity that was first recognized by the World Health Organization Classification of Tumors of the Central Nervous System in 2016. The majority of MVNT cases reported were supratentorial in location and only a small subset of cases included infratentorial involvement. In the supratentorial, MVNT is often a nidus for seizure and surgical resection is for seizure control. Infratentorial MVNT lesions are typically not or only mildly symptomatic; thus, surgical intervention may not be warranted. Here we describe the clinical course of a patient who was found to have a cerebellar vermis lesion that consistent with infratentorial MVNT. CASE REPORT A 41-year-old man sought care due to new onset headache. A brain magnetic resonance imaging (MRI) exam revealed a coalescence of bubble-like cystic lesions in the cerebellar vermis that were T1 hypointense, T2/Flair hyperintense without contrast enhancement. Initially, the lesions were attributed to neurocysticercosis but work-up was not supporting the diagnosis. MRA of head and neck found no cerebral stenosis or vascular malformation. The unique MRI features support infratentorial MVNT diagnosis. Disease course, work-up and MRI features are not consistent with low grade glioma, subacute ischemia infarct, demyelinating disease or chronic fungal or parasite infection. Brain MRI surveillance has completed every 6 months; no interval change to the cerebellar vermis lesions has been seen over past two years. Clinically, the patient has been doing well and his headache has resolved. DISCUSSION MRI features of MVNT are predominantly mixed solid and cystic, bubble-like, T2/Flair-hyperintense, T1 hypointense lesions in the deep cortical region and superficial white matter without contrast enhancement. This case demonstrates that although no specific criteria to diagnose MVNT, neurologists and neuro-oncologists should be aware of the distinguishing radiographic features, which can help patients avoid unnecessary testing and potentially harmful interventions.

UNRAVELING THE CAUSE OF A KINDRED WITH CHRONIC CANDIDIASIS

<h3>Introduction</h3> Chronic mucocutaneus candidiasis (CMC) is a clinical syndrome characterized by invasive chronic fungal infections involving skin, nails, and mucosal tissues. Advancements in genetic testing have aided in identification of underlying molecular causes; however challenges arise when variants of uncertain significance are identified in genes of interest. Our case highlights the importance of family history in genotype-phenotype correlation leading to reclassification of a novel variant in a rare immune deficiency. <h3>Case Description</h3> A 67-year-old female is referred for evaluation of chronic candidiasis including vaginitis, onychomycosis, stomatitis, gingivitis requiring teeth removal, and recurrent esophageal structuring requiring balloon dilation. She developed fluconazole resistance and treatment includes a combination of nystatin, clotrimazole, itraconazole, and in severe cases, amphotericin. She had no clinically significant history of bacterial or viral infections. Medical history included melanoma, cervical and breast cancers. Immune evaluation including HIV testing, tetanus and pneumococcal titers, total complement, lymphocyte flow cytometry and mitogen/antigen proliferation were unremarkable. Her immunoglobulins were notable for a low IgM of 43mg/dL (reference 57-237mg/dL), and diphtheria titer was low at 0.036IU/mL (reference >/= 0.100IU/mL). Gene sequencing revealed a variant of uncertain significance in STAT1 c.200A>C (p.Gln67Pro). Family history was notable for CMC in multiple relatives across four generations. Family sequencing was positive for the same STAT1 mutation in all affected members and negative for one unaffected member. <h3>Discussion</h3> Dominant STAT1 gain-of-function mutations, often in the coiled-coil domain, are an established cause of CMC. The outlined case represents a novel N-terminal domain mutation, initially classified as a variant, but reclassified as pathogenic following kindred sequencing.