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Working on mycetoma diognosis, treatment and epidemiology

Goal: diagnosis, treatment and epidemiology

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Ahmed Hassan Fahal
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Mycetoma is a neglected chronic and granulomatous infection primarily associated with the fungal pathogen Madurella mycetomatis. Characteristic of this infection is the formation of grains. However, the processes leading to grain formation are not known. In this study, we employed a proteomic approach to characterise M. mycetomatis grain formation in Galleria mellonella larvae and map the processes leading to grain formation over time. For this, at 1 day, 3 days and 7 days post-inoculation, proteins from grains and hemolymph were extracted and analysed by label-free mass spectrometry. A total of 87, 51 and 48 M. mycetomatis proteins and 713, 997, 18 G. mellonella proteins were found in grains on day 1, 3 and 7 post-inoculation respectively. M. mycetomatis proteins were mainly involved in cellular metabolic processes and numerous enzymes were encountered. G. mellonella proteins were primarily involved in the nodulation process. The proteins identified were linked to nodulation and grain formation and four steps of grain formation were identified. The results of this proteomic approach could in the future be used to design novel strategies to interfere with mycetoma grain formation and to combat this difficult to treat infection.
Ahmed Hassan Fahal
added 2 research items
The draft genomes of three fungal clinical isolates of Madurella mycetomatis from patients with mycetoma are presented. No finished genome is currently available for this important fungus. Therefore, the addition of these new draft genomes will help us better understand the diversity and pathogenicity of this important species.
Mycetoma is considered a neglected tropical disease globally. However, data on its burden and the associated complications in Uganda are limited. Hence we aimed to estimate its burden in Uganda. Firstly, a systematic PubMed search for all studies of any design on mycetoma in Uganda without restriction to the year of publication was conducted. A retrospective review of all the biopsy reports at the Pathology Reference Laboratory, Department of Pathology, Makerere University, Kampala, Uganda from January 1950 to September 2019 was conducted to identify any reports on mycetoma histological diagnosis. During the 70-years study period, 30 cases were identified by the literature review, with 249 additional cases identified by review of biopsy reports (total of 279 cases). The average incidence was estimated at 0.32/100,000 persons and prevalence of 8.32/100,000 persons per decade. However, there was a general decline in the number of cases detected recently. Males and the age group of 21–30 years were the most affected by mycetoma in Uganda, and only 7% of the cases were children. The highest number of cases was recorded from Kampala (n = 30) and Jinja (n = 19) districts. The majority of the cases (68%) were referred from surgical units. The foot was the most affected part of the body (72%). Ten per cent of the cases had bone involvement of which 58% required amputation. Fungi were the most common causative agents (89%) followed by Nocardia species (5%) and Actinomycetes (4%). The index of clinical suspicion of mycetoma was low (45%) with a very large differential diagnosis. Mycetoma is a relatively rare disease in Uganda, mostly caused by fungi, and there is a big gap in data and epidemiological studies. More systematic studies are warranted to define the true burden of mycetoma in Uganda.
Ahmed Hassan Fahal
added 3 research items
Currently, there is a massive gap the mycetoma knowledge in particular in its epidemiological characteristics, the infection route, the predisposing factors and the host susceptibility. With this background, the present cross-sectional descriptive entomological study was conducted to determine the possible role of arthropod vectors in the transmission of eumycetoma as well as the knowledge, attitude and practice (KAP) among the villagers towards that in a mycetoma endemic village at Sennar State, Sudan. The study showed an abundance of indoors and outdoors arthropod vectors, and that included ticks, mosquitoes, sandflies, cockroaches and houseflies in the studied area. Ticks were more frequent, and they belonged to three genera and four species, and the later included Hyalomma (H.) anatolicum (11.03%), Hyalomma (H.) rufipes (0.67%), Rhipicephalus (R.) everts (73.1%) and Amblyoma (A.) lepidium (15.2%). The different types of the collected arthropod vectors were pooled in groups, and each group was screened for the presence of the Madurella (M.) mycetomatis DNA, the most frequent causative agents of eumycetoma in the studied area. The DNA was extracted, and amplification of the genomic rRNA genes was done by using universal pan fungal primers and specific M. mycetomatis primers. One pool containing R. evertsi DNA samples and one sample of H. Rufipes DNA gave positive results following PCR amplification of the universal fungal positive primers while H. rufipes sample gave positive results for M. mycetomatis using a specific primer. An association between the animals’ dungs, ticks and mycetoma transmission can be suggested from this study. However, further in-depth studies are needed to verify that. Author summary Mycetoma is a severely neglected tropical disease characterised by painless subcutaneous tumour-like swellings frequently noted in the extremities. There is a massive knowledge gap in transmission, infection route, and historically, it is believed to be associated with minor trauma caused by thorn pricks. This study was designed to determine the possible role of arthropods in mycetoma transmission in an endemic area in Sudan during the cold dry season. Pools of medically important arthropods were screened for mycetoma causative agents using DNA based method. The villagers’ habits and knowledge on arthropod vectors were examined using a pre-designed questionnaire. The results showed various presences of many arthropod vectors. Ticks were found in high prevalence, and densities in domestic animals found inside houses and the villagers had high contact level with the ticks in comparison to other vectors. The study reports for the first time, the detection of the causative agents of mycetoma in a pool of ticks. More studies on the possible role of ticks in the transmission of mycetoma diseases are badly needed to delineate the possible role of ticks on transmission of mycetoma.
The use of the Sensititre™ YeastOne™ YO10 Alamar Blue assay for the in vitro susceptibility testing of Madurella mycetomatis was evaluated in M. mycetomatis isolates with and without pyomelanin secretion. Pyomelanin secretion did not influence visual endpoint reading, however, it caused a shift in peak absorbance from 570 nm to 620 nm when read spectrophotometrically. Therefore, when choosing the method for end-point reading the presence of pyomelanin should be considered.
Emmanuel Edwar Siddig
added a research item
Mycetoma is a devastating neglected tropical disease, caused by various fungal and bacterial pathogens. Correct diagnosis to the species level is mandatory for proper treatment. In endemic areas, various diagnostic tests and techniques are in use to achieve that, and that includes grain culture, surgical biopsy histopathological examination, fine needle aspiration cytological (FNAC) examination and in certain centres molecular diagnosis such as PCR. In this retrospective study, the sensitivity, specificity and diagnostic accuracy of grain culture, surgical biopsy histopathological examination and FNAC to identify the mycetoma causative organisms were determined. The histopathological examination appeared to have better sensitivity and specificity. The histological examination results were correct in 714 (97.5%) out of 750 patients infected with Madurella mycetomatis, in 133 (93.6%) out of 142 patients infected with Streptomyces somaliensis, in 53 (74.6%) out of 71 patients infected with Actinomadura madurae and in 12 (75%) out of 16 patients infected with Actinomadura pelletierii. FNAC results were correct in 604 (80.5%) out of 750 patients with Madurella mycetomatis eumycetoma, in 50 (37.5%) out of 133 Streptomyces somaliensis patients, 43 (60.5%) out of 71 Actinomadura madurae patients and 11 (68.7%) out of 16 Actinomadura pelletierii. The mean time required to obtain the FNAC result was one day, and for the histopathological examinations results it was 3.5 days, and for grain it was a mean of 16 days. In conclusion, histopathological examination and FNAC are more practical techniques for rapid species identification than grain culture in many endemic regions.
Ali mahmoud mohammed edris
added a research item
Mycetoma is a persistent, progressive granulomatous inflammatory disease caused either by fungi or by bacteria. Characteristic of this disease is that the causative agents organise themselves in macroscopic structures called grains. These grains are surrounded by a massive inflammatory reaction. The processes leading to this host tissue reaction and the immunophenotypic characteristics of the mycetoma granuloma are not known. Due to the massive immune reaction and the tissue remodeling involved, we hypothesised that the expression levels of interleukin-17 (IL-17) and matrix metalloprotease-9 (MMP-9) in the mycetoma granuloma formation were correlated to the severity of the disease and that this correlation was independent of the causative agent responsible for the granuloma reaction. To determine the expression of IL-17 and MMP-9 in mycetoma lesions, the present study was conducted at the Mycetoma Research Centre, Sudan. Surgical biopsies from 100 patients with confirmed mycetoma were obtained, and IL-17 and MMP-9 expression in the mycetoma granuloma were evaluated immunohistochemically. IL-17 was mainly expressed in Zones I and II, and far less in Zone III. MMP-9 was detected mainly in Zones II and III, and the least expression was in Zone I. MMP-9 was more highly expressed in Actinomadura pelletierii and Streptomyces somaliensis biopsies compared to Madurella mycetomatis biopsies. MMP-9 levels were directly proportional to the levels of IL-17 (p = 0.001). The only significant association between MMP9 and the patients’ characteristics was the disease duration (p<0.001). There was an insignificant correlation between the IL-17 levels and the patients’ demographic characteristics.
Ahmed Hassan Fahal
added 3 research items
Mycetoma is a neglected tropical disease endemic in tropical and subtropical countries, particularly Sudan. The disease is characterised by the triad of painless subcutaneous mass, multiple sinuses and discharge that contain grains. It is a chronic, debilitating disease most commonly affecting the feet or hands and leads to substantial morbidity, loss of function and even amputation. It predominantly affects poor, rural populations and patients typically present late with advanced disease and complications. In this descriptive cross-sectional study, we characterise the disabling consequences of mycetoma. The study included 300 patients; 228 (76%) male and 72 (24%) female with confirmed mycetoma seen at the Mycetoma Research Centre, University of Khartoum, Sudan in the period May 2016 and January 2017. The study design was based upon the International Classification of Functioning, Disability and Health, examining the impact of mycetoma on eight life domains. Our major finding is that mycetoma is a significantly disabling disease. Over 60% of the study population (181 patients) had moderate impairment or difficulty in at least one domain variable. The important disability was mobility impairment and walking difficulty that was reported in 119 patients (39.7%). There was significant pain associated with mycetoma lesions in 103 patients (34%), challenging the traditional view of mycetoma as a painless disease. The economic burden was also found to be substantial, with 126 patients (46.7%) reporting barriers to their ability to sustain themselves. This is the first study evaluating the disabling consequences of mycetoma and shows clear areas for intervention and further research. Options for mitigating social and economic impacts include routine integration of analgesia and physiotherapy into treatment protocols, and adapting educational provision and working practices based on disability assessment. Our data show that mycetoma is a public health issue with direct implications on quality of life.
Determine if the Sensititre YeastOne YO10 Alamar blue assay can be used to determine the in vitro susceptibility of M. mycetomatis towards several antifungal agents. • Assess if pyomelanin formation interferes with the various endpoint read-out systems, by comparing isolates secreting pyomelanin with isolates which do not secrete pyomelanin Madurella mycetomatis (M.mycetomatis) is the major causative agent of eumycetoma. Eumycetoma is a neglected, inflammatory tropical infection characterized by painless lesions, grains and draining sinuses. Currently, susceptibility testing for M. mycetomatis is not routinely performed. This is possibly due to the need to use hyphal suspension as a starting material, the slow growth rate, labour-intensiveness and the need to use expensive dyes for endpoint visualization. Furthermore, pyomelanin is produced by several of the isolates, which might hamper the use of other viability dyes in in vitro susceptibility testing. Commercial systems such as the Sensititre YeastOne YO10 are available but are currently not used in clinical practice with regards to eumycetoma. • Eight pyomelanin producing (P1, MM25, MM30, MM44, MM45, MM49, MM55, MM68) and eight non-pyomelanin producing (MM14,MM22,MM50, MM52, MM54, MM58, MM64, MM83) M. mycetomatis isolates were used in this study. • In vitro susceptibilities of 16 clinical isolates of M. mycetomatis were determined with the Sensititre YeastOne Alamar blue susceptibility assay following manufacturer's instructions. The Minimum Inhibitory concentrations, (MICs) were determined by visual reading, SWIN reading and spectrophotometry. • The present data suggest the Sensititre YeastOne YO10 is suitable for the susceptibility testing of M. mycetomatis and could vital in resource-limited setting • M. mycetomatis isolates are susceptible to azoles and amphotericin B but not echinocandins and 5-flucytosine • Pyomelanin secretion should be taken into consideration when performing susceptibility testing, especiaally in the choice of reading wavelength Table 2: Comparison of the different endpoint read-out methods for Sensititre YeastONE assay for isolates of M.mycetomatis • Pyomelanin secretion causes a shift in absorbance peak • M. mycetomatis is most susceptible towards the azole class of antifungal agents • Different MICs were obtained with different read-outs system • Better agreement between visual and SWIN endpoints compared to visual and spectrophotometer and/or SWIN
Emmanuel Edwar Siddig
added a research item
Mycetoma is a serious neglected tropical disease, characterised by various disabilities and high morbidity. Numerous causative organisms of fungal or bacterial origin are implicated in causing mycetoma. Accurate identification of the causative organism is mandatory for proper treatment and management. Currently, the available diagnostic tests for mycetoma are invasive, tedious, of low sensitivity and specificity and not available in the mycetoma endemic areas. In this communication, we report the Mycetoma Research Centre (MRC), Khartoum, Sudan experience on the fine needle aspiration for cytology (FNAC) technique for the identification of the mycetoma causative organisms based on the cytological reports at the MRC Biobank in the period between 1991-2017. The sensitivity and specificity of the technique for the identification of Madurella mycetomatis was 88.7% and 57.3 %, respectively. For Actinomadura madurae it was 28.7% and 96.6%, respectively. Furthermore, it was 74.1% and 88.9%, respectively for Streptomyces somaliensis and 46.7% and 99.5%, respectively for Actinomadura pelletieri. From this study, it can be concluded that the technique is reasonably accurate in the identification of mycetoma causative organisms, rapid, minimally invasive, and cost-effective procedure. It can be used for the diagnosis of mycetoma in rural areas. The use of the ultrasound-guided aspiration may improve its accuracy.
Ahmed Hassan Fahal
added a research item
A 60-year-old male farmer presented with tongue swelling of 1-month duration. Local oral clinical examinations showed a painless firm mass in the anterolateral aspect of the anterior third of the tongue. Fine needle aspiration for cytology confirmed the diagnosis of tongue actinomycetoma due to Actinomadura madurae. The patient underwent wide local excision under general anesthesia and had an uneventful postoperative recovery. He was started on amikacin sulfate 15 mg/kg daily and cotrimoxazole 15 mg/kg twice per day for 6 months. The lesion healed completely, with no evidence of recurrence at 6-month follow-up. The route of infection in this patient is unclear; however, direct traumatic inoculation is the most likely route. To the authors' knowledge, this is the first report of tongue mycetoma in the medical literature.
Ahmed Hassan Fahal
added 2 research items
Mycetoma is a chronic infective condition of tropical and subtropical regions. It is commoner in males, especially those in their third or fourth decade who work on the land. The clinical triad of subcutaneous nodule, sinuses and discharge usually leads to diagnosis; the disease is commonly painless. Treatment is by extensive surgical excision of afected areas and may include limb amputation. Recurrence is common, rates ranging from 20 to 90 per cent. Medical treatment may be used on its own or as an adjunct to surgery. Although such therapy may cure over half of those with actinomycetoma (caused by bacteria, mainly aerobic actinomycetes), those afected by eumycetoma (caused by fungi) have a poorer prognosis and may require many years of drug therapy.
Ahmed Hassan Fahal
added 2 research items
Mycetoma is a unique neglected tropical disease which distributed worldwide and endemic in tropical and subtropical regions. This disease is caused by a large number of micro-organisms of fungal (eumycetoma) or bacterial (Actinomycitoma) origins. The disease is characterized by a swelling in the cutaneous and subcutaneous tissues, with the formation of sinuses tract in some patients with numerous deformities and disabilities. Mycetoma infection affects all ages. The diagnosis of the mycetoma is based on identification of the causative organism and the disease extension which in turn considered as the first steps in the management of the affected patients and eventually predicting disease treatment outcome and prognosis. Different diagnostic tools were developed that aimed to identify the causatives agent. These include direct microscopy, Fine needle aspiration, Imprint cytology, histopathological, culturing techniques and molecular identification. Since histopathology is continues to be a rapid diagnostic tool as well as cost effective means of providing a presumptive or/and in some instances a definitive diagnosis of an invasive mycetoma infection, as well as it able to detect the causative agents invasion of tissues and vessels as well as host tissue reaction to the causative agents, however no way to replace the culture and molecular diagnosis that remain the most powerful tools for the definitive diagnosis of the causative agents. In our clinical setting at Mycetoma Research center the histopathology report, considered as a powerful tool as it include a comment stating the morphological appearance of the causative agents and the type of the host tissue reactions as well as it stated clearly the possible differential diagnosis. In this review we will discuss varies histopathological appearance of mycetoma causative agents as well as the common used histochemical stains that can aid in the diagnosis and the host tissue reaction to varies causative agents.
Ahmed Hassan Fahal
added a research item
Mycetoma is a tropical neglected disease characterized by large subcutaneous lesions in which the causative organisms reside in the form of grains. The most common causative agent is Madurella mycetomatis. Antifungal therapy often fails due to these grains, but to identify novel treatment options has been difficult since grains do not form in vitro. We recently used Galleria mellonella larvae to develop an in vivo grain model. In the current study, we set out to determine the therapeutic efficacy of commonly used antifungal agents in this larval model. Pharmacokinetics of ketoconazole, itraconazole, voriconazole, posaconazole, amphotericin B, and terbinafine were determined in the hemolymph of G. mellonella larvae. Antifungal therapy was given either therapeutically or prophylactic on three consecutive days in therapeutically equivalent dosages. Survival was monitored for 10 days and colony-forming units (cfu) and melanization were determined on day 3. Measurable concentrations of antifungal agents were found in the hemolymph of the larvae. None of the azole antifungal agents prolonged survival when given therapeutically or prophylactically. Amphotericin B and terbinafine did prolong survival, even at concentrations below the minimal inhibitory concentration of M. mycetomatis. The cfu and melanization did not differ between any of the treated groups and phosphate-buffered saline (PBS) treated groups. Grains were still present in surviving larvae but appeared to be encapsulated. This study demonstrated for the first time a comparison between the efficacy of different antifungal agents toward grains of M. mycetomatis. It appeared that amphotericin B and terbinafine were able to prolong larval survival.
Ahmed Hassan Fahal
added a research item
Mycetoma is a unique neglected disease, endemic in many tropical and subtropical regions, characterized by devastating deformities, disability, high morbidity and serious negative socioeconomic impacts on patients, families and community. It enjoys meager attention by health and social sectors across the world, as it is a non-glorious disease. Mycetoma commonly affects young adults and children of low socioeconomic status from rote rural areas in poor countries and it is an excellent example of a neglected tropical disease.
Ahmed Hassan Fahal
added a research item
The Mycetoma Research Centre (MRC), University of Khartoum, a WHO Collaborating Centre on Mycetoma in collaboration with the Ministry of Health, White Nile State, the Association of Aid & Relief, Japan (AAR), the Institute of Endemic Diseases (IEND), University of Khartoum, Bakht EL Ruda University and Yanabee Alard Foundation had conducted a medical and health mission to Um Garr island region, the White Nile State, Sudan in the period 15-17th November. This is the sixth mission to the region.
Ahmed Hassan Fahal
added a research item
One hundred and fifty patients with histologically proven gastrointestinal tract (GIT) cancer, 150 patients with a variety of other malignancies and 150 normal subjects were screened for human immunodeficiency virus (HIV) and hepatitis B sero-markers. Only one patient with nasopharyngeal carcinoma proved to be HIV seropositive. Hepatitis B surface antigen (HBsAg) was detected in 18% (n = 26) of the GIT cancer patients, in 16% (n = 24) of the other cancers group and in 12% (n = 20) of the control. There was no significant difference between the three groups (P > 0.1). The HBsAg was detected mainly in patients with primary hepatocellular (25%), gastric (12%), rectal (10%) and colonic carcinoma (8%). Hepatitis B core antibody (HBc AB) was detected in 12% of the GIT cancer patients, in 11% of the other cancers patients and in 13% of the control. In this study, there was no association between HIV, hepatitis B infections and GIT cancer.
Ahmed Hassan Fahal
added a research item
Background: Mycetoma is a badly neglected tropical disease, characterized by enormous deformities, disfigurement and disabilities if untreated early. Frequently, the majority of the mycetoma patients present late with advanced disease, and the only available treatment for them will be amputation of the affected part. Aim: This study aimed at producing a health-promoting film to be used to improve the knowledge, attitude and practice (KAP) of a targeted population in one of the mycetoma endemic villages at Sennar State, Sudan. Materials and Methods : A 26 - minute drama film on a mycetoma patient journey from a small painless mass to advanced disease till lower limb amputation due to missinformation and negligence was performed. Professional actors and cinema work team were employed in the film production. It was filmed in one of the mycetoma endemic areas. A cohort of 250 individuals from two mycetoma endemic villages were included in this study. A closed ended pre-designed questionnaire was used to collect data from the targeted population. The collected data included demographic characteristics, knowledge, attitudes and practices towards mycetoma. The data was collected before and after the film was shown. Results: In this study, 218/250 responded to the questionnaire with a response rate of 87%. Fifty-five percent of the respondents were males, 21.6% were farmers, 29.4% were students and 29.4% were unemployed. The film had improved the KAP of the targeted population hence it can be used as a health educational material in other mycetoma endemic areas in the Sudan.
Ahmed Hassan Fahal
added 2 research items
Thyroid function was assessed in seventy two patients with various types of mycetoma. There was no evidence of clinical or biochemical thyroid dysfunction in these patients. The symptoms encountered in some of the mycetoma patients mimic those of hypothyroidism should be attributed to other factors possibly mental depression and apathy.
Dual infection with tuberculosis and mycetoma has not been reported in literature to date. This communication is a report on two patients with such infection. It indicates the serious impact of the dual infection as each of them augments the pathological effects of the other.
Ahmed Hassan Fahal
added 2 research items
Mycetoma is a chronic infectious disease of the subcutaneous tissue with a high morbidity. This disease is most commonly seen in countries between 30°N and 15°S of the equator , but cases have also been seen in Europe and the USA. Due to the lack of proper prevalence data, currently the true burden of this disease is not known. Mycetoma can be caused by a large variety of microorganisms, both bacteria and fungi. Treatment of the disease depends on the etiology of the causative agent. Actinomycetoma is usually treated with antibiotics only and has a decent cure rate; eumycetoma is treated with a combination of antibiotics and surgery. Unfortunately, for eumycetoma, recurrent infections are common and amputations are still needed in a large proportion of the patients.
Abstract On28thMay2016,mycetomawasrecognizedasaneglectedtropicaldiseasebytheWorld HealthOrganization.Thiswastheresultofa4-yearjourneystartinginFebruary2013with a meeting of global mycetoma experts. Knowledge gaps were identified and included the incidence, prevalence, and mapping of mycetoma; the mode of transmission; the development of methods for early diagnosis; and better treatment. In this review, we review the road to recognition, the ISHAM working group meeting in Argentina, and we address the progress made in closing the knowledge gaps since 2013. Progress included adding another 9000 patients to the literature, which allowed us to update the prevalence map on mycetoma. Furthermore, based on molecular phylogeny, species names were corrected and four novel mycetoma causative agents were identified. By mapping mycetoma causative agents an association with Acacia trees was found. For earlydiagnosis,threedifferentisothermalamplificationtechniquesweredeveloped, and novel antigens were discovered. To develop better treatment strategies for mycetoma patients, in vitro susceptibility tests for the coelomycete agents of black grain mycetoma weredeveloped,andthefirstrandomizedclinicaltrialforeumycetomastartedearly2017.
Ahmed Hassan Fahal
added 3 research items
This paper reports 2 hitherto undescribed complications of mycetoma, urinary extravasation and expectoration of mycetoma grains due to cutaneo-urethral and cutaneo-pleuro-bronchial fistulae, respectively. The first patient had an infection with Actinomadura madurae which started in the foot and had spread progressively to involve the whole limb, anterior abdominal wall, perineum and urethra. The second patient had Madurella mycetomatis infection of the hand and, in spite of extensive treatment, the infection had spread to the axilla, chest wall, lung and bronchial tree. Both patients died of the sequelae of these complications. The pathogenesis of these unusual complications is discussed.
Ahmed Hassan Fahal
added 3 research items
The ultrasonographic appearance of mycetoma is described in this prospective study. One hundred patients with foot swellings had sonographic evaluation of the swelling and surgical excision within 2 weeks of ultrasonography. The histopathological findings were compared with the preoperative images. Some of the excised swellings and grains were also imaged and compared with the in vivo findings. The mycetoma grains, their capsules and the accompanying inflammatory granulomas have characteristic ultrasonographic appearances. In eumycetoma lesions, the grains produce numerous, sharp hyper-reflective echoes and there are single or multiple thick-walled cavities with no acoustic enhancement. In actinomycetoma, the findings are similar but the hyper-reflective echoes are fine, closely aggregated and commonly settle at the bottom of the cavities. None of the non-mycetoma foot swellings (which included lipoma, ganglion, foreign body granuloma and others) studied had these features. Ultrasonography is simple, non-invasive, quick, reproducible and acceptable to patients. Mycetoma has characteristic ultrasonographic features. Furthermore, ultrasonography delineates the extent of mycetoma more accurately than clinical examination alone.
We report 4 patients with mycetoma caused by Madurella mycetomatis who presented with cystic lesions unassociated with overlying sinuses. The lesions were successfully removed surgically.
Ahmed Hassan Fahal
added 4 research items
Currently, therapy of black-grain mycetoma caused by Madurella mycetomatis consists of extensive debridement of the infected tissue combined with prolonged antifungal therapy with ketoconazole or itraconazole. In the present study, the in vitro activity of the new triazole isavuconazole toward M. mycetomatis was evaluated. Isavuconazole appeared to have high activity against M. mycetomatis, with MICs ranging from ≤0.016 to 0.125 μg/ml. Due to its favorable pharmacokinetics, isavuconazole could be a promising antifungal agent in the treatment of mycetoma.
The management of patients with mycetoma depends on accurate identification of the causative organisms and of the extent of disease involvement along the different tissue planes. Disease involvement cannot accurately be assessed with the available diagnostic tools, so in this study we set out to evaluate the effectiveness of MRI in the diagnosis and management of mycetoma. Forty-two patients with confirmed mycetoma had MRI examination of the affected parts. A grading system, The Mycetoma Skin, Muscle, Bone Grading System (MSMBS), was used to describe and grade disease severity on the basis of MRI findings. The logistic regression test was used to correlate the clinical and MRI findings. The study showed that MRI can help in the diagnosis and management of mycetoma patients. The dot-in-circle sign, conglomerated foci with low signal intensity and macro- and micro-abscesses on a background of a hypointense matrix are all diagnostic of mycetoma. In patients with mycetoma, the MSMBS can grade disease severity, compare patients and help to manage them. Further studies are needed to determine to what extent the grading system can be used to determine a patient's prognosis.
Ahmed Hassan Fahal
added a research item
Mycetoma Patient Support Program: A Systems Approach to Mycetoma Reduction and Prevention in Sudan
Ahmed Hassan Fahal
added 2 research items
Mycetoma is a progressive and destructive chronic granulomatous subcutaneous inflammatory disease caused by bacteria and fungi. The genetic determinants for susceptibility to and the development of mycetoma are unclear. Polymorphisms in genes encoding for cytokines and chemokines usually influence the efficiency of the immune response to infection and are associated with disease susceptibility and progression. Therefore, we hypothesized that polymorphisms of CC chemokine ligand 5 (CCL5) and interleukin-10 (IL-10) promoter regions might contribute to the initiation, susceptibility, and severity of eumycetoma. This case-control study included 149 mycetoma patients and 206 healthy matched controls. In the study population, three functional single nucleotide polymorphisms (SNPs) in CCL5 and two in IL-10 were genotyped using polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). Significant differences in allele distribution were demonstrated for CCL5 -28 C/G (P < 0.0001), CCL5 In1.1 T/C (P < 0.0001) and IL-10 -592 A/C. Since in previous studies it was demonstrated that the genotypes obtained for CCL5 and IL-10 were connected with CCL5 and IL-10 production we measured the serum levels of CCL5 and IL-10 in mycetoma patients and healthy controls. Elevated serum levels for both CCL5 and IL-10 were found in mycetoma patients and we describe that genetic differences in CCL5 and IL-10 are associated with the development of the mycetoma granuloma.
Mycetoma is a major mycological health problem in many tropical and subtropical areas and Sudan is considered the mycetoma homeland. In the Sudan, Mycetoma is endemic in Central, and Western parts of the country. It affects different ethnic groups with evidence of familial trends. The frequency of HLA-DRB1 and HLADQB1 alleles in Sudanese patients with eumycetoma (n=53) and matched healthy control (n=31) was determined using polymerase chain reaction-Sequence specific primer (PCR-SSP) technique. The frequency of HLA-DRB1*13 allele was significantly higher in mycetoma patients (P<0.044) while the frequency of HLA DQB1*06 was not significantly higher in the patients compared with the control group (P<0.460). On the other hand, a non-significant increase in the frequencies of HLA-DRB1*4, HLA-DRB1*7 alleles were detected in patients when compared with the controls, p=0.498, OR=1.0209, 95%IC, 0.372-3.931 and p=0.434, OR=1.381, 95%IC, 0.387-4.924, respectively. Several alleles showed non-significant association with the presence/ absence of clinical mycetoma.
Ahmed Hassan Fahal
added 3 research items
In this short communication, we report on a 25-year-old male patient who presented with a longstanding painless swelling under the tongue. It was of a gradual onset and course, but 2 months before presentation it suddenly increased in size. Local examination revealed a tender firm pigmented mass in the midline of the mouth floor. The differential diagnosis included dermoid cyst, salivary glands tumours, mucocele or vascular anomaly. The investigations done were not conclusive. He underwent surgical exploration, and mycetoma was a surgical surprise. Although mycetoma is common problem in the tropics, such a presentation is a rarity. In tropical and subtropical regions, mycetoma should be considered in the differential diagnosis of oral cavity masses.
Mycetoma is a chronic, specific, granulomatous progressive, and destructive inflammatory disease of mainly the foot caused by either fungi (eumycetoma) or bacteria (actinomycetoma) [1]. Mycetoma is endemic in many tropical and subtropical regions, and it prevails in what is known as the mycetoma belt, which stretches in bands between the latitudes of 15° South and 30° North of the equator. With massive international travel, it also has been occasionally reported from different temperate regions [1]. The triad of a painless subcutaneous mass, multiple sinus formation, and purulent or sero-purulent discharge that contains grains is characteristic of mycetoma. It usually spreads to involve the skin, deep structures, and bone-producing massive deformities. Due to these deformities, mycetoma has a high morbidity rate, with a huge impact on the patient, family, and the community [1].
Eumycetoma is a traumatic fungal infection in tropical and subtropical areas that may lead to severe disability. Madurella mycetomatis is one of the prevalent etiologic agents in arid Northeastern Africa. The source of infection has not been clarified. Subcutaneous inoculation from plant thorns has been hypothesized, but attempts to detect the fungus in relevant material have remained unsuccessful. The present study aims to find clues to reveal the natural habitat of Madurella species using a phylogenetic approach, i.e. by comparison of neighboring taxa with known ecology. Four species of Madurella were included in a large data set of species of Chaetomium, Chaetomidium, Thielavia, and Papulaspora (n = 128) using sequences of the universal fungal barcode gene rDNA ITS and the partial LSU gene sequence. Our study demonstrates that Madurella species are nested within the Chaetomiaceae, a family of fungi that mainly inhabit animal dung, enriched soil, and indoor environments. We hypothesize that cattle dung, ubiquitously present in rural East Africa, plays a significant role in the ecology of Madurella. If cow dung is an essential factor in inoculation by Madurella, preventative measures may involve the use of appropriate footwear in addition to restructuring of villages to reduce the frequency of contact with etiologic agents of mycetoma. On the other hand, the Chaetomiaceae possess a hidden clinical potential which needs to be explored.
Ahmed Hassan Fahal
added 2 research items
Author Summary Eumycetoma is a mutilating fungal disease of mainly the foot and is found in (sub)tropical regions such as Sudan. At the moment it is not understood why some people develop eumycetoma and others not. In the regions were eumycetoma is prevalent many other infections are also found. These infections could alter the immune system which makes people more or less susceptible in obtaining another infection. One of the infections with such an effect is Schistosomiasis. In Africa, eumycetoma is found in regions were schistosomiasis is prevalent. In this study we show that eumycetoma patients more often have antibodies against Schistosoma species, than healthy controls from the same region. In contrast, eumycetoma patients did not have more often antibodies against Toxoplasma species. This might implicate that schistosomiasis predisposes eumycetoma development. If schistosomiasis indeed predisposes eumycetoma development, eradicating Schistosoma in a population could also lower the number of eumycetoma cases in that area, which in the end could lead to intervention strategies not only for schistosomiasis but also for eumycetoma.
Mycetoma is a debilitating disease with a highly particular geographical distribution. The mycetoma belt circles the entire world just above the equator and defines the region with the highest prevalence and incidence. Although the disease is seen in Central America, India and all across Africa, Sudan seems to be the homeland of mycetoma. Mycetoma is an infectious disease caused either by bacteria (actinomycetoma) or true fungi (eumycetoma). In Sudan most cases are caused by the fungal species Madurella mycetomatis. The precise natural habitat of this fungus is still an enigma, but its DNA can easily be found in soil and plant samples in endemic areas. Although the entire human population in these areas are in regular contact with the fungus, most individuals are unaffected. Thus mycetoma is an ideal clinical and experimental model system for the study of host-pathogen interactions. Also, given its relative importance locally, improvements in clinical and laboratory diagnostics and knowledge of the epidemiology of the disease are badly needed. This chapter describes the current state of affairs in the field of eumycetoma caused by M. mycetomatis. The value of laboratory research on this disease and future perspective for control and prevention of the infection are discussed.
Ahmed Hassan Fahal
added 2 research items
To investigate the genetic determinants for developing tuberculosis in Sudan. Case study of 232 patients with tuberculosis and 206 healthy matched controls from Sudan. In the study population, three single nucleotide polymorphisms (SNPs) in the promoter regions of CCL5 and two in the promoter region of IL-10 were genotyped using polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). These five SNPs influence the expression of these genes. There were significant differences in allele distribution for CCL5 -28 C/G (rs 2280788) and IL-10 -592 A/C (rs1800872) in patients with tuberculosis compared with healthy controls. This indicates that the genotypes obtained for CCL5 and IL-10 are associated with an increased risk of developing active TB.
Ahmed Hassan Fahal
added 2 research items
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Ahmed Hassan Fahal
added 2 research items
Ahmed Hassan Fahal
added 10 research items
It is still challenging and difficult to treat patients with eumycetoma; the current treatment has many side effects and has proven to be expensive and characterized by high recurrence rate, hence the poor patients' treatment compliance. Most of the patients are of low socio-economic status, have many financial constraints and hence, many of them rely on alternative and herbal medicine for the treatment of their disease. With this background, the current study was conducted to determine the prevalence of herbal medicine usage among patients with eumycetoma. This cross-sectional, observational, questionnaire-based study was conducted at the Mycetoma Research Center, University of Khartoum, Khartoum, Sudan. A convenience cohort of 311 patients with confirmed eumycetoma was invited to participate in the study after informed consent. The study showed that 42.4% of the study population used herbal medicine for the treatment of eumycetoma at some stage of their illness. The commonly used herbs were Moringa oleifera, Acacia nilotica, Citrullus colocynthis and Cuminum cyminum. Most of the patients claimed no benefits from the herbal treatment. Ninety one patients (29.3%) had encountered complications with herbal treatment. The high prevalence of herbal treatment encountered in the study can be explained by the patients' dissatisfaction with the current medical therapeutic modalities. To reduce the high prevalence of herbal medicine usage, governmental control and health policies are mandatory; likewise, native healers need to be educated in that. Moringa oleifera was the commonly used herb in this study and many reports claimed medicinal properties of this tree; hence, further in-depth studies to determine the active ingredients in the different parts of the tree and its effect are required.
1683 RESULTS CONCLUSIONS WHO recognized mycetoma as one of 17 neglected tropical diseases (NTDs) worldwide. Studies revealed a soil-borne mediated or thorn prick-mediated origin of mycetoma, but no studies are available to investigate the effect of soil type and Acacia distribution on mycetoma in Sudan. Here, we report efforts to investigate risk factors associated with mycetoma risk in Sudan using ecological niche modeling. Records of mycetoma cases were obtained from the scientific literature, PubMed, and GIDEON. Acacia records were obtained from the Global Biodiversity Information Facility. We developed ecological niche models (ENMs) based on digital GIS data layers summarizing soil, land-surface temperature, and greenness, summarizing environmental variation across Sudan. ENMs calibrated in endemic districts were transferred across all of Sudan, and suggested that greatest risk was in a belt across central and southern Sudan. We visualized mycetoma in environmental dimensions, and the results revealed that mycetoma in ecologically diverse landscapes under wide ranges of environmental conditions. We tested niche similarity between Acacia and mycetoma, and found significant niche similarity. These results revealed contributions of different environmental factors to mycetoma risk, identify suitable environments for disease emergence, raise the concerns for mycetoma-acacia association, and provide steps towards a robust, predictive risk map for the disease.
Ahmed Hassan Fahal
added 2 research items
Madurella mycetomatis is the main causative organism of eumycetoma, a persistent, progressive granulomatous infection. After subcutaneous inoculation M. mycetomatis organizes itself in grains inside a granuloma with excessive collagen accumulation surrounding it. This could be contributing to treatment failure towards currently used antifungal agents. Due to their pivotal role in tissue remodelling, matrix metalloproteinases-2 (MMP-2) and 9 (MMP-9) or tissue inhibitor of metalloproteinases (TIMP) might be involved in this process. Local MMP-2 and MMP-9 expression was assessed by immunohistochemistry while absolute serum levels of these enzymes were determined in mycetoma patients and healthy controls by performing ELISAs. The presence of active MMP was determined by gelatin zymography. We found that both MMP-2 and MMP-9 are expressed in the mycetoma lesion, but the absolute MMP-2, -9, and TIMP-1 serum levels did not significantly differ between patients and controls. However, active MMP-9 was found in sera of 36% of M. mycetomatis infected subjects, whereas this active form was absent in sera of controls (P<0.0001). MMP-2, MMP-9, and TIMP-1 polymorphisms in mycetoma patients and healthy controls were determined through PCR-RFLP or sequencing. A higher T allele frequency in TIMP-1 (+372) SNP was observed in male M. mycetomatis mycetoma patients compared to controls. The presence of active MMP-9 in mycetoma patients suggest that MMP-9 is activated or synthesized by inflammatory cells upon M. mycetomatis infection. Inhibiting MMP-9 activity with doxycycline could prevent collagen accumulation in mycetoma, which in its turn might make the fungus more accessible to antifungal agents.
Mycetoma is a tropical disease which is caused by a taxonomically diverse range of actinomycetes (actinomycetoma) and fungi (eumycetoma). The disease was only recently listed by the World Health Organization (WHO) as a neglected tropical disease (NTD). This recognition is the direct result of a meeting held in Geneva on February 1, 2013, in which experts on the disease from around the world met to identify the key research priorities needed to combat mycetoma. The areas that need to be addressed are highlighted here. The initial priority is to establish the incidence and prevalence of the disease in regions where mycetoma is endemic, prior to determining the primary reservoirs of the predominant causal agents and their mode of transmission to susceptible individuals in order to establish novel interventions that will reduce the impact of the disease on individuals, families, and communities. Critically, economical, reliable, and effective methods are required to achieve early diagnosis of infections and consequential improved therapeutic outcomes. Molecular techniques and serological assays were considered the most promising in the development of novel diagnostic tools to be used in endemic settings. Improved strategies for treating eumycetoma and actinomycetoma are also considered.
Ahmed Hassan Fahal
added 3 research items
Treatment of mycetoma depends on the causative organism and since many organisms, both actinomycetes (actinomycetoma) and fungi (eumycetoma), are capable of producing mycetoma, an accurate diagnosis is crucial. Currently, multiple diagnostic tools are used to determine the extent of infections and to identify the causative agents of mycetoma. These include various imaging, cytological, histopathological, serological, and culture techniques; phenotypic characterisation; and molecular diagnostics. In this review, we summarize these techniques and identify their merits and pitfalls in the identification of the causative agents of mycetoma and the extent of the disease. We also emphasize the fact that there is no ideal diagnostic tool available to identify the causative agents and that future research should focus on the development of new and reliable diagnostic tools.
Medical treatment of mycetoma depends on its fungal or bacterial etiology. Clinically, these entities share similar features that can confuse diagnosis, causing a lack of therapeutic response due to inappropriate treatment. This review evaluates the response to available antimicrobial agents in actinomycetoma and the current status of antifungal drugs for treatment of eumycetoma.
Emmanuel Edwar Siddig
added 2 research items
Eumycetoma is a progressive and destructive chronic granulomatous subcutaneous inflammatory disease caused by certain fungi, the most common being Madurella mycetomatis. The host defence mechanisms against fungi usually range from an early non-specific immune response to activation and induction of specific adaptive immune responses by the production of Th-1 and Th-2 cytokines. The aim of this study is to determine the levels of Th-1 and Th-2 cytokines in patients infected with Madurella mycetomatis, and the association between their levels and disease prognosis. This is a descriptive cross-sectional study conducted at the Mycetoma Research Centre, University of Khartoum, Sudan, where 70 patients with confirmed M. mycetomatis eumycetoma were enrolled; 35 with, and 35 without surgical excision. 70 healthy individuals from mycetoma endemic areas were selected as controls. The levels of serum cytokines were determined by cytometric bead array technique. Significantly higher levels of the Th-1 cytokines (IFN-γ, TNF-α, IL-1β and IL-2) were recorded in patients treated with surgical excision, compared to those treated without surgical excision. In contrast, the Th-2 cytokines (IL-4, IL-5, IL-6 and IL-10) were significantly lower in patients treated with surgical excision compared to those treated without surgical excision. In conclusion, the results of this study suggest that cell-mediated immunity can have a role to play in the pathogenesis of eumycetoma.
Ahmed Hassan Fahal
added 2 research items
In 2013, the World Health Organization (WHO) recognized mycetoma as one of the neglected tropical conditions due to the efforts of the mycetoma consortium. This same consortium formulated knowledge gaps that require further research. One of these gaps was that very few data are available on the epidemiology and transmission cycle of the causative agents. Previous work suggested a soil-borne or Acacia thorn-prick-mediated origin of mycetoma infections, but no studies have investigated effects of soil type and Acacia geographic distribution on mycetoma case distributions. Here, we map risk of mycetoma infection across Sudan and South Sudan using ecological niche modeling (ENM). For this study, records of mycetoma cases were obtained from the scientific literature and GIDEON; Acacia records were obtained from the Global Biodiversity Information Facility. We developed ENMs based on digital GIS data layers summarizing soil characteristics, land-surface temperature, and greenness indices to provide a rich picture of environmental variation across Sudan and South Sudan. ENMs were calibrated in known endemic districts and transferred countrywide; model results suggested that risk is greatest in an east-west belt across central Sudan. Visualizing ENMs in environmental dimensions, mycetoma occurs under diverse environmental conditions. We compared niches of mycetoma and Acacia trees, and could not reject the null hypothesis of niche similarity. This study revealed contributions of different environmental factors to mycetoma infection risk, identified suitable environments and regions for transmission, signaled a potential mycetoma-Acacia association, and provided steps towards a robust risk map for the disease.
Ahmed Hassan Fahal
added 17 research items
Mycetoma is a chronic inflammatory disease, which can be caused by bacteria or fungi. It is characterized by large subcutaneous lesions, with a mutilating effect. It mostly affects the feet and hands, but other body parts can be effected as well. The masses can be large and often effect the functionality of the affected limbs (1) . Bacterial mycetoma is amendable to medical treatment only, and good response rates are obtained. In contrast, fungal mycetoma cannot be cured by medication only, and a combination of surgery and antifungal treatment is recommended (1) . This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
Eumycetoma is a chronic fungal infection characterised by large subcutaneous masses and the presence of sinuses discharging coloured grains. The causative agents of black-grain eumycetoma mostly belong to the orders Sordariales and Pleosporales. The aim of the present study was to clarify the phylogeny and taxonomy of pleosporalean agents, viz. Madurella grisea, Medicopsis romeroi (syn.: Pyrenochaeta romeroi), Nigrograna mackinnonii (syn. Pyrenochaeta mackinnonii), Leptosphaeria senegalensis, L. tompkinsii, and Pseudochaetosphaeronema larense. A phylogenetic analysis based on five loci was performed: the Internal Transcribed Spacer (ITS), large (LSU) and small (SSU) subunit ribosomal RNA, the second largest RNA polymerase subunit (RPB2), and translation elongation factor 1-alpha (TEF1) gene. In addition, the morphological and physiological characteristics were determined. Three species were well-resolved at the family and genus level. Madurella grisea, L. senegalensis, and L. tompkinsii were found to belong to the family Trematospheriaceae and are reclassified as Trematosphaeria grisea comb. nov., Falciformispora senegalensis comb. nov., and F. tompkinsii comb. nov. Medicopsis romeroi and Pseudochaetosphaeronema larense were phylogenetically distant and both names are accepted. The genus Nigrograna is reduced to synonymy of Biatriospora and therefore N. mackinnonii is reclassified as B. mackinnonii comb. nov. Mycetoma agents in Pleosporales were phylogenetically quite diverse despite their morphological similarity in the formation of pycnidia, except for the ascosporulating genus Falciformispora (formerly in Leptosphaeria). Most of the species diagnosed from human mycetoma were found to be related to waterborne or marine fungi, suggesting an association of the virulence factors with oligotrophism or halotolerance.
Abstract Accurate identification of mycetoma causative agent is a priority for treatment. However, current identification tools are far from being satisfactory for both reliable diagnosis and epidemiological investigations. A rapid, simple, and highly efficient molecular based method for identification of agents of black grain eumycetoma is introduced, aiming to improve diagnostic in endemic areas. Rolling Circle Amplification (RCA) uses species-specific padlock probes and isothermal DNA amplification. The tests were based on ITS sequences and developed for Falciformispora senegalensis, F. tompkinsii, Madurella fahalii, M. mycetomatis, M. pseudomycetomatis, M. tropicana, Medicopsis romeroi, and Trematosphaeria grisea. With the isothermal RCA assay, 62 isolates were successfully identified with 100% specificity and no cross reactivity or false results. The main advantage of this technique is the low-cost, high specificity, and simplicity. In addition, it is highly reproducible and can be performed within a single day.
Ahmed Hassan Fahal
added 4 research items
Abstract Appropriate diagnosis and treatment of eumycetoma may vary significantly depending on the causative agent. Up to date, the most common fungus causing mycetoma worldwide is Madurella mycetomatis. This species fails to express any recognizable morphological characters and reliable identification can therefore only be achieved with the application of molecular techniques. Recombinase polymerase amplification (RPA) and loop-mediated isothermal amplification (LAMP) are proposed as alternatives to phenotypic methods. Species-specific primers are developed to target the rDNA internal transcribed spacer (ITS) regions of M. mycetomatis. Both isothermal amplification techniques show high specificity and sufficient sensitivity to amplify fungal DNA and proved to be appropriate for detection of M. mycetomatis. Diagnostic performance of the techniques is assessed in comparison to conventional PCR using biopsies from eumycetoma patients. RPA is reliable and easy to operate and has a potential to be implemented in mycetoma endemic areas. The techniques could be expanded to detect fungal DNA from environmental samples.
Background: Though serodiagnosis of actinomycetoma is established, that of eumycetoma due to Madurella mycetomatis is limited because of lack of pure antigen. Reliable rapid tests are needed to make an accurate timely diagnosis. The purpose of this study is to detect antigen parts of M. mycetomatis, which act specifically with M. mycetomatis antibodies. Methods: Cytoplasmic antigen was prepared from molecularly identified cultures of M. mycetomatis by sonica-tion, ultracentrifugation, dried, weighed and appropriately reconstituted. M. mycetomatis cytoplasmic antigen were separated using 12% sodium dodecyl sulfate-polyacrylamide gel, and immunoblotting to detect the reactive ones. Immunoblotting was carried out in nitrocellulose strips containing different molecular size. Sera from patients and co-patients as control were used. Results: When stained with Coomassie brilliant blue R 250 seven molecular weights appeared but only three, 45, 60, 95 kDa reacted with M. mycetomatis patients few from control group, one from a malaria patient. No reactive band was observed with sera from actinomycetoma, Aspergillus flavus-associated aspergillosis, schis-tosomiasis, leishmaniasis, fungal sinusitis nor healthy controls. Conclusions: Specific fractions of M. mycetomatis antigen which were demonstrated by immunoblotting showed 75% sensitivity and 95% specificity. The true negative tests were 14 patients (32.5%). This also means that immunoblotting is reasonably reliable in diagnosis and follow-up of eumycetoma patients.
Ahmed Hassan Fahal
added 2 research items
Mycetoma can be caused by bacteria (actinomycetoma) or fungi (eumycetoma) and typically affects poor communities in remote areas. It is an infection of subcutaneous tissues resulting in mass and sinus formation and a discharge that contains grains. The lesion is usually on the foot but all parts of the body can be affected. The causative microorganisms probably enter the body by a thorn prick or other lesions of the skin. Mycetoma has a worldwide distribution but is restricted to specific climate zones. Microbiological diagnosis and characterisation of the exact organism causing mycetoma is difficult; no reliable serological test exists but molecular techniques to identify relevant antigens have shown promise. Actinomycetoma is treated with courses of antibiotics, which usually include co-trimoxazole and amikacin. Eumycetoma has no acceptable treatment at present; antifungals such as ketoconazole and itraconazole have been used but are unable to eradicate the fungus, need to be given for long periods, and are expensive. Amputations and recurrences in patients with eumycetoma are common.