An overview of mycetoma and its diagnostic dilemma: Time to move on to advanced techniques.

The neglected tropical disease mycetoma can become extremely devastating, and can be caused both by fungi and bacteria; these are popularly known as eumycetoma and actinomycetoma respectively. The classical triad of the disease is subcutaneous swelling, multiple discharging sinuses and the presence of macroscopic granules. The present study aims to highlight the existing diagnostic modalities and the need to incorporate newer and more advanced laboratory techniques like pan fungal/pan bacterial 16S rRNA gene polymerase chain reaction (PCR) and sequencing, Matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS), rolling circle amplification (RCA), loop-mediated isothermal amplification (LAMP) and recombinase polymerase amplification (RPA). It is important for the medical team to be aware of the various diagnostic options (both existing and future), so that diagnosis of such a debilitating disease is never missed, both by clinicians and microbiologists/pathologists. The newer diagnostic methods discussed in this article will help in rapid, accurate diagnosis thus facilitating early treatment initiation, and decreasing the overall morbidity of the disease. In the Indian context, newer technologies need to be made available more widely. Making clinicians aware and promoting research and development in mycetoma diagnostics is the need of the hour.

Mycetoma in north-western Yemen: Clinico-epidemiological and histopathological study.

Background Mycetoma is widespread in Yemen; however, there are only a few documented reports on the entity from this geographical area. Methods A prospective study of 184 cases of mycetoma (male 145 and female 39) from different regions of north-western Yemen was conducted between July 2000 and May 2014. Clinical profile was recorded in a standardized protocol. The diagnosis was based on clinical features, X-ray studies, examination of grains, and histopathology. Results Eumycetoma was diagnosed in 129, caused by Madurella mycetomatis in 124, Leptosphaeria senegalensis in one and pale grain fungus in four, whereas actinomycetoma occurred in 55, caused by Streptomyces somaliensis in 29, Actinomadura madurai in nine, Actinomadura pelletieri in one, and Nocardia in sixteen. Eumycetoma cases were treated with prolonged course of antifungal drugs, mostly ketoconazole, with itraconazole being used in four patients, along with excision or debulking. Results were better when antifungal drugs were given two to three months before surgery and in those who received itraconazole. Actinomycetoma cases were initially treated with co-trimoxazole monotherapy; later streptomycin was added in 30 cases. Six patients who did not show adequate improvement and two others from the start were treated with modified Welsh regimen and with good results. Limitations Identification of different causative agents was done by histopathology and could not be reconfirmed by culture. Conclusion Mycetoma is widespread in north-western Yemen with a higher incidence of eumycetoma and a majority of the cases were caused by Madurella mycetomatis. Modified Welsh regimen in actinomycetoma and itraconazole with excision in eumycetoma showed the best results.

Afectación cutánea en las micosis profundas: una revisión de la literatura. Parte 1: micosis subcutáneas / Cutaneous involvement in the deep mycoses: a literature review. Part I-subcutaneous mycoses

Las micosis profundas son infecciones poco frecuentes en nuestro medio. Se presentan principalmente en pacientes inmunodeprimidos o en regiones de climas tropicales, que abarcan las micosis subcutáneas y las micosis sistémicas. Las micosis subcutáneas o por implantación siempre producen signos de afectación cutánea. En la primera parte de esta revisión se realizará una revisión de las principales micosis subcutáneas: esporotricosis, cromoblastomicosis, micetomas, feohifomicosis, hialohifomicosis y lacaziosis. Reconocer y tratar estas micosis subcutáneas de forma precoz es importante, ya que a menudo están asociadas a una alta morbilidad

The deep mycoses are uncommon in our setting. These fungal infections occur mainly in immunosuppressed patients or in tropical climates, and include subcutaneous infections and systemic infections. The skin is always involved in the former. In the first part of this review, we describe the main subcutaneous mycoses: sporotrichosis, chromoblastomycosis, mycetoma, phaeohyphomycosis, hyalohyphomycosis, and lacaziosis. Early recognition and treatment is important, as these infections are frequently associated with high morbidity

Nocardial mycetoma: diverse clinical presentations.

Nocardia spp are gram-positive, aerobic, acid-fast bacteria which exist as saprophytes in nature. Invasive disseminated infections are particularly common in immunocompromised or debilitated hosts. Superficial infections with Nocardia spp occur as a result of local trauma and contamination of the wound. Clinically, it presents as acute infection (abscesses or cellulitis), mycetoma, or sporotrichoid infection. Differential diagnosis includes eumycetoma, chromomycosis, blastomycosis, coccidioidomycosis, sporotrichosis, tuberculosis, botryomycosis, syphilis, yaws, and neoplasia. Its diagnosis is confirmed by demonstrating the causative organism in exudates (as granules), tissue specimens, or cultures. Early diagnosis will obviate need for drastic surgical measures as early institution of chemotherapy is effective in most patients. However, its diagnosis is often delayed due to diverse clinical presentations and for want of clinical suspicion, particularly in non-endemic areas. This paper presents 4 clinical forms of this not so uncommon disease, emphasizing the importance of high index of clinical suspicion, especially in non-endemic regions; and the significance of repeated examination of exudates for Nocardia granules for an early diagnosis.

Mycetoma sans sinuses.

Mycetoma is a chronic suppurative infection involving the skin, subcutaneous tissue and bone. The hallmark of mycetoma is tumefaction, draining sinuses and the presence of microcolonies called grains. Sinuses develop in all patients with mycetoma within a year of the appearance of the lesion. The following case is reported as no sinuses had developed despite the presence of the lesion for 9 years, posing a diagnostic dilemma.

[Anti-Nocardia brasiliensis antibodies in patients with actinomycetoma and their clinical usefulness]. / Anticuerpos anti-Nocardia brasiliensis en pacientes con actinomicetoma y su utilidad clínica.

Anti-Nocardia brasiliensis antibodies quantification and its clinical utility was confirmed in this study. A protein cellular extract from a N. brasiliensis strain named HUJEG-1 and registered at the ATCC # 700358 was used in a western blot assay to identify the immunodominant antigens. The protein P24 was selected to set up an ELISA test because it exhibit no cross-reaction with sera from tuberculosis and leprosy patients. A purified protease was also used as antigen in the ELISA test to compare its utility. Sera from N. brasiliensis mycetoma persons gave absorbance values above 0.3 when the disease was active using the P24 as antigen, these values decreased after patients completed their medical treatment. Anti-protease antibodies showed great variation and absorbance values similar to the healthy controls. We confirmed the clinical usefulness of the ELISA test both in serodiagnosis and in assessing the response to medical treatment. This is the first sensitive and specific serologic test for routine clinical laboratory.

Enzyme-linked immunosorbent assay for serological diagnosis of Nocardia brasiliensis and clinical correlation with mycetoma infections.

We previously identified three immunodominant antigens obtained from a Nocardia brasiliensis cell extract and recognized by sera from mycetoma patients (M. C. Salinas-Carmona, L. Vera, O. Welsh, and M. Rodríguez, Zentralbl. Bakteriol. 276:390-397, 1992). In the present work, we obtained a crude extract from a mass culture of N. brasiliensis HUJEG-1 and purified two immunodominant antigens, the 26- and 24-kDa proteins, by using simple physiochemical techniques. With these antigens, we developed a conventional solid-phase enzyme-linked immunosorbent assay and tested 30 serum samples from mycetoma patients, 29 from tuberculosis patients, 24 from a leprosy group, and 31 from healthy individuals. Our results show for the first time statistically significant differences in serology among these groups. All mycetoma patients with a positive culture for N. brasiliensis had absorbance values higher than 0.3. On the other hand, the mycobacterium-infected patients as well as the healthy individuals all had absorbance values below that level. Moreover, we found a close correlation between the clinical condition of the mycetoma patients and the anti-26- and anti-24-kDa protein antibody concentrations. We therefore propose the use of this assay in routine clinical laboratories to confirm the diagnosis of N. brasiliensis infection in human mycetoma cases. In addition, the possible application of this assay in the serodiagnosis of Nocardia asteroides infection is also discussed.