IS MYCETOMA ENDMIC IN EGYPT ? By Prof.Dr. M. Taha

Mycetoma is subcutanous infectious granulomatous chronic disease which may spread to adjacent skin and bone. Generally mycetoma characterized by : - Tumefaction - Draining sinuses - Grains

Gill 1842 was the first who describe the disease during his work in Madura,india Carter 1874 named the disease mycetoma and proved its mycotic nature . The first cases in Africa was described in Sengal in 1894 and in Sudan1904 . The division of the disease into separate categories dependent on fungal etiology (eumycetoma)and actinomycotic etiology (actinomycetoma) was first suggested by Pinory 1913.

Mycetoma occurs unevenly worldwide but is endemic in tropical and sub-tropical as Sudan,Somalia, Singal India,Yemen,Mexico,Venezuela Colombia and Argentina in region Known as mycetoma belt

In Egypt there is no avialable literature (to my knowledge) about mycetoma except those wrote by El Mofty et al 1956 and El Zawahry 1967 Recently tens of mycetoma cases were recieved in my private lab for mycological examination which means that there is more cases of mycetoma in Egypt

Causes of mycetoma 1- Actinomadura madurae 3- Nocadia brasiliensis Actinomycetoma Caused by species of areobic Actinomycetes as : 1- Actinomadura madurae 3- Nocadia brasiliensis 4- Nocardia asteroides 5- Streptomyces somaliensis

Causes of mycetoma Eumycetoma : caused by species of fungi as: 1-Madurella mycetomatis 2-Madurella grisea 3-Leptosphaeria senegalensis 4-Pseudallescheria boydii 5-Acremonium (A.faciform, A.kiliense, A.recifei) 6-Aspergillus spp. (A. nidulans A. flavus)

The main cause of mycetoma in Egypt according to 27 cases examined during 3 years (2010 - 2013 ) were : Actinomadura madurae (4) Nocardia asteroides (1) Madurella mycetomatis (17) Madurella grisea (1) Four cases had grains but the organism could not be isolated

Clinical presentation Most patients seek care after long periods of disease The first sign noticed is the presence of a painless swelling,vesicles small abscesses or boils Fistula with drainig of viscous or purulent exudate and granules(grains) usually predominant

The lesion grow slowly with darker aspect and firmer consistency than surrounding skin The lesion become painful at the late stage due to the involvment of nerves Process involve from 3 month to years About 70 % of mycetoma involve the foot while hands ,knee ,legs and head are less common

% No. of cases Affected organs 66.66 18 Foot 18.51 5 Hand 7.40 Leg 2 Leg 3.70 1 Knee Head and neck

Male predominance is a constant findings Male predominance is a constant findings. 24 male and 3 female were recorded in the examined 27 cases, from them 23 were egyptian,3 from Yemen and one from Somalia. All examined cases affected the adult between 20-50 y and most of them are agricultural workers

Eumycetoma grow slowly with less destructive less suppurative, less inflammatory with more swelling and late bone affection than actinomycetoma

Actinomycetoma caused by N.madurae

Actinmycetoma caused by Nocadia asteroides

Eumycetoma caused by M.mycetomatis

Eumycetoma caused by M.mycetomatis

Eumycetoma caused by M. mycetomatis

Black grain eumycetoma with darker aspect than surrounding skin

Eumycetoma caused by M.mycetomatis

Knee mycetoma caused by M.mycetomatis

Eumycetoma showing purulunt exudate and black grains

Diagnosis 1-Macro and micro examination of grains Collection of grains done by covering draining sinus opening with sterile pads for 8-12 h . It examined for color ,size and consistency which differ accordinge the causative agent. Grains examined microscopicaly after crushed between two slides with KOH or stained by gram

Main characters of grains according organisms Microscopy Consistency Size Color M.mycetomatis Broad compact colored hyphae with vesicles in some hard 0.7- 5 Black M.grisea compact broad hyphae weakly pigmented in centre soft 0.5 - 2 L.senegaliensis Loose netork of hyphae in centre and vesicel in peripheral 0.5- 2 Acremonium sp Allescheria boydii Network of hyaline hyphae 0.5-1 white A.madurae Thin hyphae in network 0.5- 5 White A.pelletiere thin mycelial filaments 0.3- 0-5 Red N.brasiliensis thin hyphae >0.5 Y.white N.asteroids network of thin hyphae 0.15-2 S.somaliensis 0.5-2 Yellow

2- Culture grains as well as exudate are cultured on suitable media 2- Culture grains as well as exudate are cultured on suitable media . In case of black grains Sabouraud’s dextrose agar and dermatophyte test medium is suitable while for white grains sabouraud’s or malt extrat agar as well as blood agar are used. Incubation time and degree of temperature is differ from bacterial isolates or fungi .

3- Radiological findings CT and MRI typically demonstrated bone lesion earlier than X rays .A dot in circle sign demonstrated by MRI is consider specific for mycetoma. Ultrasonic imaging : hyperreflective echos and cavities can differentiate between mycetoma and non-mycetoma lesions

4 - Histopathology Infected tissue should be sectioned and stained with H &E, PAS and GMS. Brown-Brenn stained tissue preparation in actinomycetoma revealed gram positive filaments 5- Serology 6- Molecular

Grains of Actinomadura madurae

White grains of M.madurae crushed and stained by Gram

Cultur characters of actinomycetes isolated from examined cases Actinomadura madurae : slow growing on SDA reach 1.5 cm in weeks . Colonies are moist ,mucoid with pink colour. Old culture showed fragmentation of hyphae Nocardia asteroides : grow quickly on SDA produce pale yellow to orange colonies with cerebriform appearance .Microscopic of colonies showed delicate branching hyphae with bowlling form

Colonies of N.asteroides on SDA

Black grains from mycetoma caused by M.mycetomatis

Black grains

Microscopic of black grains after KOH preparation

Characters of Madurella spp. isolated from eumycetoma M.mycetomatis Grow on SDA and DTM in 10-20 days with brown diffuse pigment . Colonies are velvety white then become greyish to dark olive. Microscopically usually sterile showed hyphae and few chlamydospores

Madurela grisea Similar to M.mycetomatis but rapid growing white to grey colonies can not grow at 37c and oval conidia are present M.madurae assimilate lactose and not sucrose while M.grisea assimilate sucrose and not lactose

M.mycetomatis on SDA showing diffuse brown pigment

M.Maycetomatis on SDA showing velvety greyish colonies with diffuse pigment

Treatment in mycetoma a) actinomycetoma In vitro study with isolated bacteria revealed the sensitivity of A.madurae to Trimethoprime-sulphamethoxazole, Amoxicillin clavulanic acid and amikacin while N.asteroides was sensitive to ciprofloxacin and erythromycin.

Treatment of actinomycetic mycetoma usually done with combination of streptomycin and dapsone . Amikacin 15 mg/kg /d in combination with Trimethoprime-sulphamethoxazole 8-40 mg/kg/d for 5 five weeks are used in cycles . 2- 4 cycles were recommanded

b) eumycetoma In vitro study Madurella mycetomas revealed the sensitivity to itraconazole. Treatment of eumycetoma usually done by - Ketoconazole 400 mg- 800 mg daily for 9 m - Itraconazole 400 mg daily - Voriconazole 200 mg x2 /day for 3 months

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