Mycetoma

Brijesh Singh Yadav

brijeshbioinfo@gmail.com

Disease Type: Both Fungal & Bacterial Disease

Causative Agent: Actinomycotic Mycetoma, eumycetoma
Common Name: Madura Foot, Fungus ball, Aspergilloma
Disease description:
Mycetoma is a chronic, granulomatous disease of the skin and subcutaneous tissue, which
sometimes involves muscle, bones, and neighboring organs. It is characterized by
tumefaction, abscess formation, and fistulae. It typically affects the lower extremities, but
it can occur in almost any region of the body. Mycetoma predominately occurs in farm
workers, but it can also occur in the general population. The infection can be caused by
true fungi (eumycetoma) in 40%, or filamentous bacteria (actinomycetoma) in 60%.
Also known as Pulmonary aspergilloma.(1) , Mycetoma is a chronic subcutaneous
infection which results in a granulomatous inflammatory response in the deep dermis and
subcutaneous tissue, and can extend to the underlying bone. Mycetoma is characterized
by the formation of grains containing aggregates of the causative organisms that may be
discharged onto the skin surface through multiple sinuses. This disease was described
first in the mid 1800s and initially named Madura foot, after the region of Madura in
India where it first was identified. (2)
Pseudoallescheria boydii is one of many eumycetoma fungi spp. that causes the fungal
form of madura foot . The disease is characterized by a yogurt-like discharge upon
maturation of the infection.

Fig.1. Mycetoma showing numerous draining sinuses. There is destruction of bone,

distortion of the foot, and hyperplasia at the openings of the sinustracts.
2. Excised mycetoma showing a draining sinus (cut open in this preparation) containing
black grains.

Causes of Disease:
 Owing to a wound, bacteria or fungi gain entry into the skin. Approximately one month
or more after the injury, a nodule forms under the skin surface. The nodule is painless,
even as it increases in size over the following months. Eventually, the nodule forms a
tumor, or mass of abnormal tissue. The tumor contains cavities-called sinuses-that
discharge blood- or pus-tainted fluid. The fluid also contains tiny grains, less than two
thousandths of an inch in size. The color of these grains depends on the type of bacteria
or fungi causing the infection.

As the infection continues, surrounding tissue becomes involved, with an accumulation

of scarring and loss of function. The infection can extend to the bone, causing
inflammation, pain, and severe damage. Mycetoma may be complicated by secondary
infections, in which new bacteria become established in the area and cause an additional
set of problems (11).

Risk Factors:

Mycetoma typically presents in agricultural workers (hands, shoulders and back - from
carrying contaminated vegetation and other burdens), or in individuals who walk barefoot
in dry, dusty conditions. Minor trauma allows pathogens from the soil to enter the skin (6)

Causative Agent Description:

Pathogen Name: Actinomycotic Mycetoma,

Pathogen Description:

 Actinomycetoma is a mycetomal disease affecting the skin and connective tissue.

It is characterized by formation of granules containing branched filaments. The
characteristic granules formed during the course of infection drain via formation
of sinuses.
 It is researched by the Mycetoma Research Center, which is part of The
University of Khartoum, located in Khartoum, Sudan.
 Actinomadura is a genus of aerobic, Gram-positive, non-acid-fast fungi where
filaments fragment into spores. Actinomadura pelletieri is an agent of mycetoma.
 Eumycetoma

Pseudallescheria is a filamentous fungus that is found worldwide. It has so far been

isolated from soil (7), sewage, contaminated water, and the manure of farm animals. It is
an emerging opportunistic pathogen and can cause various infections in humans. The
infections caused by Pseudallescheria boydii are occasionally and wholely referred to as
pseudallescheriasis. Pseudallescheria boydii is among the causative agents of white grain
mycetoma.
Fig.1.Actinomycotic mycetoma

2.
Eumycotic mycetoma due to the fungus
Pseudallescheria boydii

3.Actinomycotic Mycetoma, Foot

Taxonomic classification:

Actinomadura is an aerobic actinomycetes, Actinomadura is a filamentous bacterium

found in soil. Although it was once believed to be a fungus, the information later attained
about its ultrastructural cellular properties showed that Actinomadura is in fact an aerobic
actinomycetes. However, for the reason that most of the diagnostic procedures related to
Actinomadura are still held in mycology laboratories in many centers.

Morphology & toxin Production:

The growth rate of Actinomadura is slow. It grows on routine mycologic or

mycobacteriologic media and under aerobic conditions. The colony has a glabrous, waxy,
membranous or mucoid, heaped and folded appearance. The color of the colony is red,
pink, yellow, orange, white, or tan. Following two weeks of incubation, aerial hyphae
may develop on the surface, particularly on Lowenstein-Jensen medium. Actinomadura is
Gram positive and nonacid-fast. The typical structures are the filaments, which are
nonfragmenting and narrow (0.5-1 µm in diameter). These filaments branch abundantly.
Chains of round conidia may occasionally be produced from the aerial hyphae,
particularly on slide cultures. (12)
Fig. At higher magnification, the colony of
organisms floats in sea of pus. Organizing
granulation tissue outlines the defect.

Fig. The tissue above the lower 1/4 of the field

is granulation tissue. The two darker zones in
the granulation tissue are areas of suppuration.
In the zone of suppuration to the left, green
arrows identify a colony of organisms. The
colony is a “grain” (mycetoma)

Taxonomic Classification:

Kingdom Fungi
Phylum Ascomycota
Class Euascomycetes
Order Microascales
Family Microascaceae
Genus Pseudallescheria

Conidiophores with conidia of Pseudallescheria boydii

Morphology:

Pseudallescheria is a homothallic fungus. Colonies of Pseudallescheria boydii grow

rapidly at 25°C. The texture is wooly to cottony. From the front, the color is initially
white and later becomes dark gray or smoky brown. From the reverse, it is pale with
brownish black zones. (9) Pseudallescheria is a filamentous fungus that is found worldwide
(8)
Taxonomic Classification:

Kingdom Fungi
Phylum Ascomycota
Class Euascomycetes
Order Microascales
Family Microascaceae
Genus Pseudallescheria

Fig. Pseudallescheria boydii

(anamorph Scedosporium apiospermum) on Sabouraud's dextrose agar showing typical
greyish-white, cottony colony with a greenish-black reverse.

Morphology and toxin production:

Pseudallescheria is a homothallic fungus. Colonies of Pseudallescheria boydii grow
rapidly at 25°C. The texture is wooly to cottony. From the front, the color is initially
white and later becomes dark gray or smoky brown. From the reverse, it is pale with
brownish black zones. (9). The morphological features of the fungomas vary between
involved organs, with those in the lung showing well-defined layers of peripheral
mycelial hypocellularity and hypercellularity consisting of anneloconidiophores and
conidia. The fungomas in all organs are derived from necrotic host tissue, which resulted
from nodular infarction due to fungal invasion and thrombosis of blood vessels. (10)

MORPHOLOGY OF THE GRAINS (GRANULES) IN MYCETOMAS:

Eumycetomas:

Madurella mycetomatis: Large granules (up to 5 mm or more) with interlacing hyphae

embedded in interstitial brownish matrix; hyphae st periphery arranged radially with
numerous chlamydospores.

Petriellidium boydii: Eosinophilic, lighter in the center; numerous vesicles or swollen

hyphae; peripheral eosinophilic fringe; other pale eumycetomas have a minimal fringe
and contain a dense mass of intermeshing hyphae.

Actinomycetomas:

Actinomadura madurae: Large (1 - 5 mm and large) and multilobulate; peripheral

basophilia and central eosinophilia or pale staining; filaments grow from the peripheral
zone.

Streptomyces somaliensis: Large (0.5 - 2 mm or more) with dense thin filaments; often
stains homogeneously; transverse fracture lines.

Nocardia brasiliensis: Small grains (approximately 1 mm); central purple zone ; loose
clumps of filaments ; Gram-positive delicate branching filaments breaking up into
bacillary and coccal forms ; Gram-negative amorphous matrix.
History:

For Eumycetoma, Gill, who worked at a dispensary in the southern Indian province of
Madura, first recognized mycetomas as a disease entity in 1842. Godfrey first
documented a case of mycetoma in Madras, India. Native peoples of the province of
Madura commonly called the disease Madura foot. In 1860, Carter, who established the
fungal etiology of this disorder, first proposed the term mycetoma. In 1872, Carter further
proposed the terms melanoid and ochroid in an attempt to classify the disease into 2
varieties on the basis of the black or pale-colored granules (i.e., grains, sclerotia)
produced by the etiologic agents. (2)

Epidemiology:
The disease is endemic in the tropics and subtropics and is named after the region of
India where it was first described in 1842.
• Although currently uncommon in temperate regions, it does occur in the
southern USA, and cases are found in the homeless, and AIDS sufferers.
• The incidence of mycetoma is likely to rise in temperate regions due to
increases in worldwide travel, and since mycoses are not notifiable, the incidence
in the UK is unknown.

Disease Transmission:

The causative organism enters through sites of local trauma (eg, cut on the hand, foot
splinter, local trauma related to carrying soil-contaminated material). A neutrophilic
response initially occurs, which may be followed by a granulomatous reaction. Spread
occurs through skin facial planes and can involve the bone. Hematogenous or lymphatic
spread is uncommon. (2)

Mechanism: Bacteria causing Actinomycetoma has a thick wall surrounding the

cytoplasmic membrane which is rich in lipid & carbohydrate compound. Some of these
compounds such as lipoarabinomamman & mycoloc acids have been identified as
virulence factors.These bacteria are capable of blocking the adequate killing mechanism
of the cells of the infected hosts.
However, it is considered that they have low pathogenic potential & most of them live as
saprophytes in the soil.(13)

Signs and symptoms of disease: Many patients have no symptoms. When symptoms do
develop, they can include:

• Cough
• Coughing up blood (seen in up to 75% of patients)
• Chest pain
• Shortness of breath
• Wheezing
 • Unintentional weight loss
• Fever(1)

Diagnosis:

Diagnosis of mycetoma is usually accomplished by radiology,ultrasound or by fine

needle aspiration of the fluid within an afflicted area of the body.

Exams and Tests

• Chest x-ray
• Chest CT
• Sputum culture
• Bronchoscopy or bronchoscopy with lavage (BAL)
• Serum precipitins for aspergillus (blood test to detect antibodies to aspergillus)(1)

Fig. H&E stained tissue section showing blacked

grained
eumycotic mycetoma caused by Madurella
mycetomatis.

Treatment:

Combating mycetoma requires both surgery and drug therapy. Surgery usually consists of
removing the tumor and a portion of the surrounding tissue. If the infection is extensive,
amputation is sometimes necessary. Drug therapy is recommended in conjunction with
surgery. The specific prescription depends on the type of bacteria or fungi causing the
disease. (11)Actinomadura madurae is usually susceptible to a combination of
streptomycin and dapsone

Single or combination treatment is used:

• Streptomycin injections
• Oral cotrimoxasol (Apo-Sulfatrim®, Bactrim®, Septrin®, Trimel®, Trisul®)
• Amikacin (Amikin®)
• Dapsone
• Rifampicin (Rifidin®)
 • Minocycline (Minomycin®, Minotabs®).
• Sulfamethoxazole

Eumycetoma is more difficult to treat.

• Itraconazole
• Ketoconazole
• Surgery to remove the affected tissue completely. These may mean amputation if
bone is involved. (3)

One proposed treatment protocol involves gentamicin, cotrimoxazole, and doxycycline(5)

Geographical Distribution:

Mycetoma, or Madura Foot, is a disease prevalent in arid and semi-arid regions around
the globe. It is found in Brazil,Mexico,the Sahel,in pan-Arabia,and in semi-arid areas of
India.It is found as far north as Romania and United States.

Eumycetoma is mainly a disease of the tropical and subtropical zones especially between
the Tropic of Cancer and the Tropic of Capricorn, that is, between the latitudes 15° S and
30° N. Eumycetoma is endemic in India, parts of Africa (eg, Sudan, Senegal, Somalia,
Nigeria, Zaire, Chad), Pakistan, Yemen, Mexico, Central America, South America (eg,
Guatemala, Venezuela, Colombia, Brazil), and Indonesia (2).

In general, the geographic distribution of the various mycetoma agents is related to the
amount of rainfall and other climatic conditions. Each geographic region has a different
list of most common agents. (2).

Disease Statistics:
• It is not endemic in New Zealand but mycetoma is occasionally diagnosed in
native Pacific Islanders.
• Mycetoma is more common in men than women; particularly those aged 20 to 50.
(3)

• The male-to-female ratio is 183:81(2).

• For eumycetoma, the disease incidence is higher in males than females, with a
ratio of 4-5:1 & in persons aged 10-40 years. . (2)

Sources:
1. Medline plus
2. eMedicine
3. Dermnet NZ
4. University of Maryland Medical Centre
5. Indian journal of dermatology, venereology and leprology
6. Patient UK
7. Summerbell, R. C., S. Krajden, and J. Kane. 1989. Potted plants in hospitals as
reservoirs of pathogenic fungi. Mycopathologia. 106:13-22.
8. Fernandez-Guerrero, M. L., P. Ruiz-Barnes, and J. M. Ales. 1987. Postcraniotomy
mycetoma of the scalp and osteomyelitis due to Pseudallescheria boydii `letter. J
Infect Dis. 156:855.
9. de Hoog, G. S., J. Guarro, J. Gene, and M. J. Figueras. 2000. Atlas of Clinical
Fungi, 2nd ed, vol. 1. Centraalbureau voor Schimmelcultures, Utrecht, The
Netherlands
10. Mycology Online-University of Adelaide, Australia
11. Health A to Z
12. Larone, D. H. 1995. Medically Important Fungi - A Guide to Identification, 3rd
ed. ASM Press, Washington, D.C.
13. Principles and Practice of Travel Medicine by Jane N. Zuckerman