A Case of Recurrent Sputum-Positive Pulmonary Tuberculosis Presenting With Pulmonary Mycetoma.

Pulmonary tuberculosis is a notorious disease as it can cause severe morbidity and mortality. In this case, we discuss a 75-year-old male tuberculosis patient from a rural area with no underlying comorbidities who failed to continue anti-tubercular medication after two months. The case discusses the diagnostic modalities confirming the diagnosis, sputum culture for Mycobacterium tuberculosis, imaging studies, including X-ray and CT of the chest, and laboratory parameters for identifying pulmonary mycetoma. The patient is now on anti-tubercular therapy (isoniazid, rifampicin, pyrazinamide, and ethambutol combination) and the anti-fungal drug itraconazole. Though pharmacotherapy for the treatment of mycetoma in patients with tuberculosis has a minimal role, the more appropriate treatment is surgical excision via lobectomy. As the occurrence of tuberculosis and mycetoma is a rare phenomenon, it is essential to rule out aspergillosis as both have similar presenting symptoms. Diagnosis of this co-infection can be the crucial difference between morbidity and mortality.

Actinomycetoma by Nocardia asteroides: A Case Report of a Unique Neglected Tropical Disease From North India.

Nocardial mycetoma is a neglected tropical disease reported worldwide, especially in tropical and subtropical regions. It is ubiquitous in nature and is a soil-borne, gram-positive, filamentous, aerobic bacteria with acute angle branching. Traumatic inoculation in endemic areas is the primary mode of infection of this debilitating disease. The clinical triad of tumefaction, draining sinus, and pus discharge with granules is very much characteristic and specific for clinching the diagnosis of mycetoma. However, the painless nature of the primary skin lesion often makes the patient present late to the clinician, often in the advanced stages of the disease. Here, we present a very intriguing case report of a young female patient who presented with a single neck nodule but was later diagnosed as a case of nocardial mycetoma. Timely diagnosis and initiation of therapy proved to be a boon for the patient with almost complete recovery within a few weeks in the form of healed skin lesions and insignificant scarring.

The performance and costs of XTT, resazurin, MTS and luciferin as viability dyes in in vitro susceptibility testing of Madurella mycetomatis.

BACKGROUND: in vitro susceptibility testing for the non-sporulating fungus Madurella mycetomatis is performed with a hyphal suspension as starting inoculum and a viability dye for endpoint reading. Here we compared the performance of four different viability dyes for their use in in vitro susceptibility testing of M. mycetomatis. METHODS: To compare the reproducibility and the agreement between the viability dyes 2,3-bis-(2-methoxy-4-nitro-5-sulfphenyl)-2H-tetrazolium-5-carboxanilide salt (XTT), resazurin, 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium salt (MTS) and luciferin, the in vitro susceptibilities of 14 genetically diverse M. mycetomatis isolates were determined for itraconazole and amphotericin B. The reproducibility, agreement, price and ease of use were compared. RESULTS: Each of the four dyes gave highly reproducible results with >85.7% reproducibility. Percentage agreement ranged between 78.9% and 92.9%. Resazurin was the most economical to use (0.0009 €/minimal inhibitory concentration [MIC]) and could be followed in real time. Luciferin omitted the need to transfer the supernatant to a new 96-well plate, but cost 6.07 €/MIC. CONCLUSION: All four viability dyes were suitable to determine the in vitro susceptibility of M. mycetomatis against itraconazole and amphotericin B. Based on the high reproducibility, high percentage agreement, price and possibility to monitor in real time, resazurin was the most suited for routine in vitro susceptibility testing in the diagnostic laboratory in mycetoma-endemic countries. Because luminescence could be measured directly without the need to transfer the supernatant to a new 96-well plate, luciferin is suitable for drug-screening campaigns. LAY SUMMARY: To determine the in vitro susceptibility testing in the non-sporulating fungus Madurella mycetomatis, a viability dye is needed for endpoint reading. In this study we tested the viability dyes XTT, resazurin, MTS and luciferin for their use in in vitro susceptibility testing. It appeared that they all could be used but there were differences in time to result and costs associated with them.

Proceedings of the Second International Meeting on Endemic Mycoses of the Americas (IMEMA), and First International Symposium on Implantation Mycoses (ISIM).

The Second International Meeting on Endemic Mycoses of the Americas (IMEMA) and the First International Symposium on Implantation Mycoses (ISIM) took place in Santiago del Estero, Argentina during September 25-27th, 2023. The conference provided a platform for researchers, clinicians, and experts to discuss the latest developments in the field of endemic and implantation mycoses. Topics included epidemiology, diagnostic advances, treatment strategies, and the impact of environmental factors in the spread of these fungal diseases. IMEMA and ISIM contributed to the regional discourse on the mycoses, emphasizing the importance of international cooperation in addressing these public health challenges.

IMEMA/ISIM, held in Santiago del Estero, Argentina, convened experts to discuss endemic and implantation mycoses, covering topics such as epidemiology, diagnostics, treatment, and advocacy. The event highlighted ongoing efforts in combating these diseases.

Combined medical-interventional approaches for the management of complex fungal balls: a case series as a viable alternative in non-surgical patients.

Intracavitary pulmonary aspergilloma is a persistent and life-threatening infection that carries a mortality rate of up to 15%. It occurs when Aspergillus species gain entry to an existing lung cavity. In the absence of definitive treatment, patients may succumb to severe complications such as massive hemoptysis, cachexia, or secondary infections. Aspergillomas often show limited response to antifungal medications, mainly due to insufficient drug concentrations within the cavities. Surgery is frequently the preferred treatment option, but it poses significant risks, and many individuals are ineligible due to underlying health issues. We present the most extensive non-surgical fungal ball cohort to date, managed using an innovative multimodal strategy that combines antifungal therapy before and after bronchoscopic debulking. This was a cross-sectional observational study. For those who cannot undergo surgery, our medical center has pioneered a multimodal approach to aspergilloma resection. This approach combines bronchoscopic endoscopy with antifungal therapy and has been applied successfully to more than 18 patients that are presented in this series. The median age of the cohort was 58 years (range: 32-73), with an equal sex distribution. The mean percent predicted FEV1 was 65.3%. The mean follow-up duration was 3.6 years (range: 0.5-10 years). The cohort receiving antifungals systematically prior to debridement showed a reduction of the pre-existing cavity (40.38 mm versus 34.02 mm, p = 0.021). Across the 18 patients during the follow-up period, 94% remained recurrence-free (defined by symptoms and radiology). Our study fills a critical knowledge gap regarding the significance of initiating antifungal treatment before bronchoscopic debulking and presents a viable approach in these cases for which there is a current unmet therapeutic need.

The use of both medical and interventional methods to treat difficult fungal masses: A collection of cases showing efficacy for patients who can't undergo surgeryIntracavitary pulmonary aspergilloma is a serious and potentially deadly infection with a death rate of up to 15%. It happens when certain types of fungi invade existing lung cavities. Without proper treatment, patients may experience severe complications like heavy bleeding from the lungs, weight loss, or other infections. Traditional antifungal medications often don't work well because they can't reach high enough concentrations in the cavities. Surgery is usually the best option, but it's risky and not possible for many due to other health problems. Our study introduces a new way to treat aspergilloma without surgery. We've treated a significant number of patients using a combination of antifungal drugs and a procedure called bronchoscopic debulking. This involves removing the fungal growth using a thin tube inserted through the airways. Our research involved observing 18 patients treated this way. They were mostly middle-aged, with equal numbers of men and women. Their lung function was moderately impaired, and we followed them for an average of 3.6 years. We found that giving antifungal drugs before the debulking procedure helped reduce the size of the cavities. After treatment, almost all patients remained free of symptoms and signs of recurrence. This study highlights the importance of starting antifungal therapy before bronchoscopic debulking and offers a promising option for patients who can't have surgery.

An updated list of eumycetoma causative agents and their differences in grain formation and treatment response.

SUMMARYIn 2023, the World Health Organization designated eumycetoma causative agents as high-priority pathogens on its list of fungal priority pathogens. Despite this recognition, a comprehensive understanding of these causative agents is lacking, and potential variations in clinical manifestations or therapeutic responses remain unclear. In this review, 12,379 eumycetoma cases were reviewed. In total, 69 different fungal species were identified as causative agents. However, some were only identified once, and there was no supporting evidence that they were indeed present in the grain. Madurella mycetomatis was by far the most commonly reported fungal causative agent. In most studies, identification of the fungus at the species level was based on culture or histology, which was prone to misidentifications. The newly used molecular identification tools identified new causative agents. Clinically, no differences were reported in the appearance of the lesion, but variations in mycetoma grain formation and antifungal susceptibility were observed. Although attempts were made to explore the differences in clinical outcomes based on antifungal susceptibility, the lack of large clinical trials and the inclusion of surgery as standard treatment posed challenges in drawing definitive conclusions. Limited case series suggested that eumycetoma cases caused by Fusarium species were less responsive to treatment than those caused by Madurella mycetomatis. However, further research is imperative for a comprehensive understanding.

Sandalwood Oils of Different Origins Are Active In Vitro against Madurella mycetomatis, the Major Fungal Pathogen Responsible for Eumycetoma.

In the search for new bioactive agents against the infectious pathogen responsible for the neglected tropical disease (NTD) mycetoma, we tested a collection of 27 essential oils (EOs) in vitro against Madurella mycetomatis, the primary pathogen responsible for the fungal form of mycetoma, termed eumycetoma. Among this series, the EO of Santalum album (Santalaceae), i.e., East Indian sandalwood oil, stood out prominently with the most potent inhibition in vitro. We, therefore, directed our research toward 15 EOs of Santalum species of different geographical origins, along with two samples of EOs from other plant species often commercialized as "sandalwood oils". Most of these EOs displayed similar strong activity against M. mycetomatis in vitro. All tested oils were thoroughly analyzed by GC-QTOF MS and most of their constituents were identified. Separation of the sandalwood oil into the fractions of sesquiterpene hydrocarbons and alcohols showed that its activity is associated with the sesquiterpene alcohols. The major constituents, the sesquiterpene alcohols (Z)-α- and (Z)-ß-santalol were isolated from the S. album oil by column chromatography on AgNO3-coated silica. They were tested as isolated compounds against the fungus, and (Z)-α-santalol was about two times more active than the ß-isomer.

Intractable Nocardial mycetoma with possible colonisation by Candida species.

A Japanese male in his 30s with no underlying medical condition presented with painless nodules after being bitten by a dog during a stay in Bali, Indonesia, 7 years earlier. He was referred to our department with multiple ulcers, nodules, and masses on the right leg. The final diagnosis was mycetoma caused by Nocardia vulneris, which may have been exacerbated by colonization of Candida parapsilosis and C. tropicalis as these yeasts were isolated by culture from the tissue. Treatment with minocycline hydrochloride and sulfamethoxazole trimethoprim showed partial efficacy, but the addition of posaconazole achieved significant efficacy. This suggests that the surmised coexistence of pathogenic yeasts of lower virulency may have made mycetoma in this case intractable.

Towards enhanced control of mycetoma: a roadmap to achieve the UN's sustainable development goals by 2030.

Mycetoma is a neglected tropical disease (NTD) with devastating morbidity and stigma. Despite increased awareness and international collaboration, the burden of mycetoma is largely unknown and diagnosis and treatment are difficult. Addressing mycetoma globally aligns with several United Nation's Sustainable Development Goals (SDGs). Little progress has been made since the WHO's NTD roadmap publication in 2020. The Global Mycetoma Working Group proposes an enhanced mycetoma-control roadmap to meet the SDGs, stimulate progress and improve the lives of patients experiencing mycetoma. By aligning mycetoma management with the goals and targets of this enhanced roadmap, it becomes possible to leverage existing resources, infrastructure and partnerships to improve the lives of affected individuals and communities. This updated assessment is designed for the benefit of health workers and providers in mycetoma-endemic areas, NTD government officials, civil society and funding and implementing agencies.

Dot in circle sign on MRI in foot mycetoma.

Mycetoma or Maduramycosis is a chronic granulomatous infectious condition encountered mostly in tropical and subtropical regions. It affects the deep subcutaneous tissues, which may progress to involve the muscles and bones later in the course of the disease. It can be caused by fungi (eumycetoma), and bacteria (actinomycetoma) predominantly affecting the foot. Demonstration of the causative agent by biopsy and microbiological studies helps to establish a confirmative diagnosis, and choosing correct antimicrobial therapy. However, it may be delayed resulting in increased patient morbidity. Thus, imaging plays a vital role in early recognition & prompt treatment, especially MRI which is a non-invasive procedure demonstrating the hallmark dot in circle sign. Here we report a case of mycetoma foot with pathognomic MRI findings.

Dermoscopy aids in lesion selection for microbiological and histopathological assessment of mycetoma.

Mycetoma, a chronic granulomatous infection of the skin and the subcutaneous tissue, is characterized by discharge of exudate containing grains. This report illustrates the importance of dermoscopy in selecting lesions for both microbiological and histopathological assessment, which are considered the gold standard of diagnosis in mycetoma.

Outcomes of pulmonary resection in pulmonary aspergilloma: A retrospective cohort study in a single tertiary-care hospital in Northern Thailand.

BACKGROUND: To date, surgery is the best approach to maximize a cure for symptomatic aspergilloma, but this is not without risk of both morbidity and mortality. The aim of this study is to present the characteristics and outcomes of 77 patients diagnosed with aspergilloma who underwent surgery at Chiang Mai University Hospital (CMUH), and to identify risk factors for composite major postoperative complications (CMPC). METHODS: This is an observational retrospective cohort study carried out at CMUH over a period of 11 years from January 1, 2010, to February 28, 2021. Patient characteristics and postoperative outcomes were studied. The primary outcomes were categorized into CMPC. Univariable and multivariable risk regression analysis were used to identify risk factors of CMPC, with risk ratio (RR) and 95% confidence intervals being calculated. RESULTS: There were 77 patients included in this study; 27 patients identified as having CMPC and 55 patients as a non-CMPC group. From the multivariable analysis, a factor associated with CMPC included perioperative FFP transfusion (risk ratio (RR) 1.01,95 % CI 1.01-1.02) and preoperative angiogram embolization (RR 8.42, 95 % CI 1.44-49.06) whereas immediate extubation (RR 0.22, 95% CI 0.06-0.81) was less likely to be associated with CMPC. There was a trend of increased risk of CMPC in patients received perioperative blood transfusion, but the data did not reach statistical significance. CONCLUSIONS: This study has identified a need for patient profiling before embarking on lung surgery for aspergilloma, to predict outcomes and allocate resources appropriately for safer surgery.

Mycetoma in Ecuador.

BACKGROUND: Previous studies on the distribution of mycetoma globally have failed to identify Ecuador as an endemic country. METHODS: We present data on 35 cases of mycetoma in Ecuador between 1955 and 2021: 5 cases from our experience and 30 cases from the literature. RESULTS: Eight cases of eumycetoma (23%) and 27 cases of actinomycetoma (77%) were diagnosed. Most cases originated from the coastal region of Ecuador. CONCLUSIONS: For the first time in an English-language publication, this communication confirms the presence of mycetoma in Ecuador, securing Ecuador's position on the global mycetoma map.

Cutaneous Hyalohyphomycosis and Its Atypical Clinical Presentations in Immunosuppressed Patients.

There has been a substantial increase in the number of cases of invasive fungal infections worldwide, which is associated with a growing number of immunosuppressed patients and a rise in antifungal resistance. Some fungi that were previously considered harmless to humans have become emerging pathogens. One of them is Purpureocillium lilacinum, a ubiquitous filamentous fungus commonly found in the environment, especially in the air and soil. P. lilacinum belongs to a bigger group of hyaline fungi that cause hyalohyphomycosis, a fungal infection caused by fungi with colorless hyphae. Although this is a heterogeneous group of fungi, there are similarities regarding their ubiquity, ways of transmission, affected patients, and difficulties in diagnostics and treatment. In hyalohyphomycosis, the skin is one of the most affected organs, which is why the involvement of dermatologists is crucial for the initial assessment, since the timely recognition and early diagnosis of this condition can prevent life-threatening infections and death. In this review, we covered cutaneous hyalohyphomycosis caused by P. lilacinum and other fungi in the same group, including Fusarium, Penicilium, Scedosporium, Scopulariopsis, Acremonium, and Trichoderma genera.

Evaluation of a computational model for mycetoma-causative agents identification.

BACKGROUND: The therapeutic strategy for mycetoma relies heavily on the identification of the causative agents, which are either fungal or bacterial. While histopathological examination of surgical biopsies is currently the most used diagnostic tool, it requires well-trained pathologists, who are lacking in most rural areas where mycetoma is endemic. In this work we propose and evaluate a machine learning approach that semi-automatically analyses histopathological microscopic images of grains and provides a classification of the disease as eumycetoma or actinomycetoma. METHODS: The computational model is based on radiomics and partial least squares. It is assessed on a dataset that includes 890 individual grains collected from 168 patients originating from the Mycetoma Research Centre in Sudan. The dataset contained 94 eumycetoma cases and 74 actinomycetoma cases, with a distribution of the species among the two causative agents that is representative of the Sudanese distribution. RESULTS: The proposed model achieved identification of causative agents with an accuracy of 91.89%, which is comparable to the accuracy of experts from the domain. The method was found to be robust to a small error in the segmentation of the grain and to changes in the acquisition protocol. Among the radiomics features, the homogeneity of mycetoma grain textures was found to be the most discriminative feature for causative agent identification. CONCLUSION: The results presented in this study support that this computational approach could greatly benefit rural areas with limited access to specialized clinical centres and also provide a second opinion for expert pathologists to implement the appropriate therapeutic strategy.

Actinomycetoma by Cellulosimicrobium cellulans in a Young Man from Guinea-Bissau: Short Literature Review Regarding a Case Report.

Mycetoma is caused by the subcutaneous inoculation of filamentous fungi or aerobic filamentous bacteria. Cellulosimicrobium cellulans is a gram-positive bacterium from the order Actinomycetales that rarely causes human disease. The diagnosis is based on the clinical presentation and identification of the causative microorganism. We present a short literature review regarding the case report of a young man diagnosed with actinomycetoma due to Cellulosimicrobium cellulans and who received treatment with an association of amikacin and sulfamethoxazole/ trimethoprim (Welsh regimen).

Sinonasal Oxalosis due to Fungal Rhinosinusitis: A Unique Case of a Destructive Pseudotumor.

Oxalosis refers to the accumulation of calcium oxalate crystals in various organs and tissues, most commonly due to Aspergillus infection involving the lung or sinonasal tract. Both invasive and noninvasive forms of fungal rhinosinusitis can be associated with calcium oxalate crystal deposition. Here, we report a unique case of sinonasal oxalosis presenting as a destructive lesion in the absence of invasive fungal disease. Due to the clinical and pathologic significance of calcium oxalate crystals as seen in this patient, specimens from the sinonasal tract should be evaluated for the presence of these crystals, which may be a surrogate marker for fungal infection and may also independently cause tissue destruction.

Mycetoma case series in Somalia.

Mycetoma is a suppurative chronic bacterial or fungal disease inoculated into the body by minor trauma which may penetrate from subcutaneous tissue to bone. Although the lower extremities are most commonly affected, rare forms can also be seen from time to time. The diagnostic triad of swelling in the affected area, multiple sinus formation, and purulent discharge with grains are typical. Definitive diagnosis is made by isolation of the causative pathogen, radiologic imaging, and histopathologic examination. Antifungal and antibacterial options are applied together with surgery. Our aim in this case series is to report and analyze 10 rare cases of mycetoma.

Invasive Eumycotic mycetoma of the nasal septum in a post-dialysis patient: A case report.

BACKGROUND: Mycetoma is a slowly progressive chronic granulomatous disease of the skin, subcutaneous tissue, and underlying or adjacent cartilage or bone. Most commonly involves the foot region. Other parts such as the knee, arm, leg, head, neck, thigh, perineum, chest, abdominal walls, facial bones, mandible, paranasal sinuses, eyelid, vulva, orbit, and scrotum are seldom affected. METHODS: This is a rare presentation of Eumycotic mycetoma involving the nasal septum. Surgical debridement is done under local anesthesia. Histopathological examination of debrided specimen guided in the diagnosis and treatment. RESULTS: Histopathological examination is the one that confirms the diagnosis and rules out the other granulomatous conditions and fungal rhinitis causing septal perforation. CONCLUSIONS: In an immunocompromised state, we know that mucormycosis and zygomycosis are known to cause aggressive complications like orbital invasion and palatal perforation by vascular route. However, other fungal infections also can lead to septal perforations whenever there is lessened resistance by the mucosal barrier due to trauma (nasal intubations).