Patients with mycetoma usually present late with advanced disease, which is attributed to lack of medical and health facilities in endemic areas, poor health education and low socio-economic status. With this background, an integrated patient management model at the village level was designed to address the various problems associated with mycetoma. The model was launched in an endemic village in the Sudan, between 2010 and 2013. This model is described in a prospective, descriptive, community-based study, aimed to collect epidemiological, ecological, and clinical data and to assess knowledge, attitude and practice (KAP) in order to design effective and efficient management measures. In this study, the prevalence of mycetoma was 14.5 per 1,000 inhabitants. The patients were farmers, housewives and children of low socio-economic status, and no obvious risk group was detected. All had surgery performed in a mobile surgical unit in the village which encouraged patients to present early with small early lesion leading to a good clinical outcome. The close contact with the Acacia tree thorns, animals and animal dung, walking bare footed and practising poor hygiene may all have contributed to the development of mycetoma in the village. Knowledge of mycetoma was poor in 96.3% of the study population, 70% had appropriate attitudes and beliefs towards interaction with mycetoma patients and treatment methods, and 49% used satisfactory or good practices in the management of mycetoma. Knowledge and practices on mycetoma were found to be significantly associated with age. Based on the KAP and epidemiological data, several health education sessions were conducted in the village for different target groups. The integrated management approach adopted in this study is unique and appeared successful and seems suitable as an immediate intervention. While for the longer term, establishment of local health facilities with trained health staff remains a priority.
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.
This prospective study contains clinical and experimental parts. In the clinical study, 125 patients given intramuscular chloroquine for malaria were followed for 2 months in order to detect local injection site complications. Adequate local antiseptic conditions were ensured before giving the injection. Twenty-three patients (18.4%) had minimal local reaction in the form of redness, induration and/or a lump. No pyogenic abscess was noted in contrast to a previous report. In the second part of the study, an experimental animal (Green monkey) was given either chloroquine phosphate, Ampiclox or normal saline intramuscularly. The injection site was later biopsied and histologically examined. Intramuscular chloroquine was found to cause severe inflammatory reactions and muscle necrosis, whereas other injections had very minimal local effects. It is concluded that intramuscular chloroquine causes muscle necrosis which may lead to acute pyogenic abscess if minimal contamination takes place.
Madurella mycetomatis is the commonest cause of eumycetoma in Sudan and other countries in tropical Africa. Currently, the early diagnosis of mycetoma is difficult. In attempting to improve the identification of M. mycetomatis and, consequently, the diagnosis of mycetoma, we have developed specific oligonucleotide primers based on the sequence of the internal transcribed spacer (ITS) regions spacing the genes encoding the fungal ribosomal RNAs. The ITS regions were amplified with universal primers and sequenced, and then two sets of species-specific primers were designed which specifically amplify parts of the ITS and the 5.8S ribosomal DNA gene. The new primers were tested for specificity with DNA isolated from human mycetoma lesions and DNA extracted from cultures of M. mycetomatis reference strains and related fungi as well as human DNA. To study the genetic variability of the ITS regions of M. mycetomatis, ITS amplicons were obtained from 25 different clinical isolates and subjected to restriction fragment length polymorphism (RFLP) analysis with CfoI, HaeIII, MspI, Sau3AI, RsaI, and SpeI restriction enzymes. RFLP analysis of the ITS region did not reveal even a single difference, indicating the homogeneity of the isolates analyzed during the current study.
Mycetoma is a unique neglected tropical disease caused by a substantial number of microorganisms of fungal or bacterial origins. Identification of the causative organism and the disease extension are the first steps in the management of the affected patients and predicting disease treatment outcome and prognosis. Different laboratory-based diagnostic tools and techniques were developed over the years to determine and identify the causative agents. These include direct microscopy and cytological, histopathological, and immunohistochemical techniques in addition to the classical grain culture. More recently, various molecular-based techniques have joined the mycetoma diagnostic armamentarium. The available mycetoma diagnostic techniques are of various specificity and sensitivity rates. Most are invasive, time consuming, and operator dependent, and a combination of them is required to reach a diagnosis. In addition, they need a well-equipped laboratory and are therefore not field friendly. This review aims to provide an update on the laboratory investigations used in the diagnosis of mycetoma. It further aims to assist practising health professionals dealing with mycetoma by outlining the guidelines developed by the Mycetoma Research Centre, University of Khartoum, WHO collaborating centre on mycetoma following a cumulative experience of managing more than 7,700 mycetoma patients.
INTRODUCTION Treatment options for the highly neglected fungal tropical disease eumycetoma are limited and poorly adapted to patients’ contexts, with surgery often required. The first-line treatment, itraconazole, thought to be 40% effective, must be taken twice daily for ≥12 months with food, making adherence difficult. An effective, affordable, context-appropriate treatment is urgently needed. The Drugs for Neglected Diseases Initiative (DNDi) repurposed the broad-spectrum antifungal agent fosravuconazole, developed by Eisai Ltd for onychomycosis. We aimed to compare two different doses of weekly fosravuconazole with standard-of-care daily itraconazole in patients with eumycetoma. METHODS This phase 2, randomised, double-blind, active-controlled, superiority trial was done at the Mycetoma Research Centre, Soba University Hospital, Sudan. Patients aged ≥15 years with a small-to-medium lesion (≥2 to <16 cm) caused by M mycetomatis requiring surgery were randomly assigned (1:1:1) to receive either 300 mg fosravuconazole weekly (group 1), 200 mg fosravuconazole weekly (group 2), or 400 mg itraconazole daily (group 3), for 12 months, together with surgery at 6 months in all groups. The primary efficacy endpoint, assessed in all patients receiving at least one dose of study drug (modified intention to treat), was complete cure at 12 months (absence of eumycetoma mass and sinuses and discharge with normal imaging; or a negative fungal culture if mass present). Safety was assessed in patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov (NCT03086226). RESULTS Between 9 May, 2017, and 10 June, 2021, 104 patients were randomised (34 to group 1, 34 to group 2, and 36 to group 3).Median age was 29.0 (IQR22.0–33.0), 23.0 (20.0–29.0) and 24.5 (19.5–33.0) years for Groups 1, 2, and 3 respectively. Complete cure rates at end of treatment were 50.0% (95% CI 32.4–67.6), 64.7% (46.5–80.3), and 75.0% (57.8–87.9) with Groups 1, 2 and 3, respectively, showing no superiority of fosravuconazole over the standard-of-care (p=0.030 for Group 2 vs Group 3; and p=0.347 for Group 1 vs Group 3; with significance level set at 0.022). Treatment-emergent adverse drug reactions were reported in one (3%) of 34 patients in group 2 (nausea or vomiting) and three (8%) of 36 patients in group 3 (cortisol decreased, QT prolonged). CONCLUSION Although not superior, fosravuconazole 200 mg seemed to have similar efficacy to itraconazole, coupled with advantages such as a weekly, not daily, administration, no food effect, and low risk for drug-drug interactions. An early access programme is under review by authorities in Sudan and a regulatory dossier and global access plan are under preparation.
Mycetoma is a neglected tropical disease, endemic in many tropical and subtropical regions, characterised by massive deformity and disability and can be fatal if untreated early and appropriately. Interleukins (IL) -35 and IL-37 are newly discovered cytokines that play an important role in suppressing the immune system. However, the expression of these interleukins in patients with Madurella mycetomatis (M. mycetomatis) induced eumycetoma has not yet been explored. The aim of this study is to determine the levels of IL-1 family (IL-1β, IL-37) and IL-12 family (IL-12, IL-35) in a group of these patients and the association between these cytokines levels and the patients' demographic characteristics. The present, case-control study was conducted at the Mycetoma Research Centre, Soba University Hospital, University of Khartoum, Sudan and it included 140 individuals. They were divided into two groups; group I: healthy controls [n = 70; median age 25 years (range 12 to 70 years)]. Group II: mycetoma patients [n = 70 patients; median age 25 (range 13 to 70 years)]. Cytokines levels were measured in sera using enzyme linked immunosorbent assay (ELISA). There was a significant negative correlation between IL-1β and IL-12 levels and lesion size and disease duration, while IL-37 and IL-35 levels were significantly positively correlated with both lesion size and disease duration. The analysis of the risk factors of higher circulatory levels of IL-37 in patients of mycetoma showed a negative significant association with IL-1β cytokine, where a unit increment in IL-1β will decrease the levels of IL-37 by 35.28 pg/ml. The levels of IL-37 among the patients with a duration of mycetoma infection ≤ 1 year were significantly low by an average of 18.45 pg/ml compared to patients with a mycetoma infection's duration of ≥ 5years (reference group). Furthermore, the risk factors of higher levels of IL-35 in mycetoma patients revealed a negative significant association with IL-12, as a unit increment in IL-12 decreases the levels of IL-35 by 8.99 pg/ml (p < 0.001). Levels of IL-35 among the patients with duration of mycetoma infection ≤ one year were significantly low on average by 41.82 pg/ml (p value = 0.002) compared to patients with a duration of mycetoma infection ≥ 5 years (reference group). In conclusion, this study indicates that both IL-35 and IL-37 are negatively associated with the levels of IL-1β and IL-12 in eumycetoma mycetoma infection; and high levels of IL-37 and IL-35 may have a negative impact on disease progression.
Mycetoma is a chronic granulomatous inflammatory disease that causes severe deformities, disabilities, with many impact on patients and family, particularly in advanced disease stages or when treatment fails. The therapeutic disease strategy heavily relies on the identification of the causative organism and the corresponding classification of the disease as eumycetoma or actinomycetoma. Various diagnostic tools are used for mycetoma differential diagnosis. Histopathology is considered to be an efficient, cost and time-effective tool for mycetoma diagnosis in endemic areas. While histology is currently, the most used diagnostic tool, it requires well-trained pathologists, and that lacks in most rural areas where mycetoma is endemic. In this communication, we present a computational method to effectively differentiate between eumycetoma and actinomycetoma from the grains features in histopathological microscopic images that is based on Radiomics and Partial Least Squares Discrimination Analysis (PLS-DA). In this work, the data were collected from the Mycetoma Research Center of Khartoum, and the proposed approach achieved mycetoma types identification with an accuracy of 91.8% and 0.836 Matthew's Correlation Coefficient (MCC). This computational tool could be of great benefit in rural areas with limited access to specialised clinical centres.
'%3e%3cpath fill='%23012169' d='M0 0v30h60V0z'/%3e%3cpath stroke='%23fff' stroke-width='6' d='m0 0 60 30m0-30L0 30'/%3e%3cpath stroke='%23C8102E' stroke-width='4' d='m0 0 60 30m0-30L0 30' clip-path='url(%23b)'/%3e%3cpath stroke='%23fff' stroke-width='10' d='M30 0v30M0 15h60'/%3e%3cpath stroke='%23C8102E' stroke-width='6' d='M30 0v30M0 15h60'/%3e%3c/g%3e%3c/svg%3e)