My name is Jessie Przyby. I am a graduate student in the Biology Department at Western Illinois University. I am interested in medical mycology because of the importance of pathogenic fungi and the need to improve diagnoses, treatment, and cures of fungal infections. My blog is an educational tool to inform people of a pathogenic fungi, Paracoccidioides.
Paracoccidioidomycosis
Paracoccidioides
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| Figure 1. Steering wheel shape of Paracoccidioides (16) |
Taxonomy: (7)
Domain: Eukarya
Kingdom – Fungi
Phylum – Ascomycota
Class – Euromycetes
Order – Onygenales
Family –Ajellomycetaceae (Onygenaceae)
Genus – Paracoccidioides
Species – brasiliensis
General Description:
Paracoccidioides belongs
to the Ascomycota phylum and is part of the Onygenales order. This specific
order is known to contain many fungal true pathogens. Adolfo Lutz discovered Paracoccidioides
in 1908 from a skin lesion (16). A true pathogen has the ability to infect not
only immunocompromised humans, but also immunocompetent people. Individuals would only
need to inhale about 12 spores to become infected with the fungus (16).
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| Figure 2. "Fungal lollipop" shape of Paracoccidioides (16) |
The fungus is predominant
in male patients. Women contain more estrogen that inhibits the transformation of
mycelium or conidia to yeast (2). A study has also shown the use of tobacco and
alcohol increases the risk of paracoccidioidomycosis (2).
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| Figure 3. Paracoccidioides mold colony at 25°C (10) |
Distribution
Paracoccidioides is
a tropical disease that is endemic and mainly limited to Central and South
America, with the highest incidence in Brazil, Colombia, Venezuela and
Argentina (Figure 4). There have been imported cases reported in the U.S., Europe, and
Asia (2). Brazil accounts for 80% of cases, followed by Colombia and Venezuela
(9). This genus accounts for the largest cause of mortality among systemic
mycoses in Brazil and causes 1.65 deaths per 1,000,000 inhabitants, which ranks
eighth on the cause of mortality from a chronic infectious disease. This soil
fungus affects approximately 10 million people (2).
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Figure 4. Geographical distribution of paracoccidioidomycosis in Central and South America (14).
Habitat
Paracoccidioides prefers damp soils with a high index of rainfall and a temperature range between 18°C and 28°C (2). This fungus has proven to live in soil near rivers and lakes and specifically indigenous to the Eucalyptus and Pimus forests. Paracoccidioides has been isolated from bat and penguin feces, squirrel monkeys, and dog food contaminated with soil (11). The organism has also been isolated from the lungs of armadillos, which can be a reservoir (5).
Look A-likes
P. brasiliensis is identified based on the morphological characteristics found in the lesions on patients. Certain patterns of this fungus may be mistaken for another type of infection (8). Paracoccidioidomycosis has been named the South American Blastomycosis. Blastomycosis means “yeast disease” caused by B. dermatitidis, which has similar symptoms and endemic regions to that of P. brasiliensis. Its “aleurioconidial state” is similar, but can differentiate in yeast phase (16).
Coccidioides – “oides” means “similar to” and “para” also means “similar to”. The name literally means like Coccidioides. Paracoccidioides means “a fungus that’s like another fungus that’s like the protozoan “Coccidia”. Paracoccidioides was mistaken in early years for Coccidioides (16).
Symptoms/Signs and Treatment
Most cases of Paracoccidioidomycosis are mild symptomatic (5). There are three different patterns of symptoms: mucocutaneous, lymphatic, and visceral. Mucocutaneous involves infections on the face, specifically around the nasal and oral orifices (Figure 5). An enlarged but painless cervical, supraclavicular, or axillary nodes characterize a lymphatic case. Visceral symptoms include enlargement of the liver, spleen, and abdominal lymph nodes, which is painful (13).
Treatments include Azoles, Amphotericin B, and Sulfonamides (13). Amphocitericin is a polyene antifungal that is used only in the treatment of severe cases (5). Itraconazole cured patients with a chronic form of the disease quicker than cotrimoxazole in a specific study that compared the two drugs in the treatment of Paracoccidioidomycosis. The side effects of itraconazole were also lower than that of cotrimoxazole (4). Vaccines have been tried in mice, but nothing is available commercially yet (11).
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Figure 5. Mucocutanous lesions on the face from Paracoccidioidomycosis (10).
Clinical Cases/Manifestations
Case Study 1: A 30-year-old male was working in a gold mine in Colombia his entire life. He went to the infectious disease outpatient clinic with a two-month history of spiking fevers, generalized lymphadenopathy (enlargement of the lymph nodes), right lower quadrant pain, diplopia (double vision), headache, and vertigo (Figure 7). He was given a physical and had a positive Romberg test result, ataxia (loss of voluntary control of muscle movements), and lymphadenopathy. A CT scan of his neck was ordered, which showed lymphadenopathy in cervical chains. A biopsy of the neck lymphadenopathy showed the steering wheel shape of P. brasiliensis, with the use of Grocott’s methenamine silver (Figure 6). The patient was treated with amphotericin B for one month. He showed a decrease in symptoms and was released and treated with voriconazole and sulfamethoxazole, but did not return for follow up visits (3).
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| Figure 6.
Arrows reveal P. brasiliensis stained with Grocott’s
methenamine silver with 40X magnification (3). |
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| Figure 7. Patient displays lymphadenopathy (3). |
Case Study 2: A 10-year-old male came to the hospital with
complaints of right knee pain and right femoral swelling for four months. There
was no history of fever. A physical examination was given. A mass in the right
inguinal region was found and pain was present in the movement of the right
knee and pelvis. The MRI revealed a femoral neck lesion and showed cortical
bone destruction with a soft tissue component. A surgical biopsy was performed and
showed giant fungal yeast cells that were consistent with
Paracoccidioidomycosis. The serum immune electrophoresis for P. brasiliensis was positive. The child
was referred to the infectious disease clinic to receive proper treatment for
Paracoccidioidomycosis (15).
Case Study 3: A 58-year-old black male presented three
painless, ulcerated, granulomatous lesions located in his mouth that had
evolved over two years. The asymmetry in his face showed edema in his lower lip
and lymphadenopathy. He has a history of smoking for more than six years, but
does not show signs of lungs alterations, cough, or fever. Biopsies of the
lesions were performed and stained with Grocott’s methenamine silver. The test
was positive for Paracoccidioidomycosis. A treatment plan of 400mg/day of
ketoconazole was given for two months. A follow-up was conducted and the oral
lesions were diminished, but the treatment continued for another six months with
no recurrent lesions (1).
Case Study 4: A 59-year-old male presented a three-month
history of anorexia, muscle weakness, weight loss, painful oral ulcers, cough,
and shortness of breath with exertion. He had a history of alcohol abuse and
smoking habit. He has worked in Brazil from 1958-1964 and in Argentina from
1979-1981. An examination showed a lesion on his nose, erythematous papular
rash (red, bumpy rash) on his scrotum, buttocks, and left legs, papules on the
soles of his feet, and a lesion on his tongue. His lower lungs revealed
crackles. Blood and urine cultures were negative. CT of the chest showed
peripheral nodules. A transbronchial bite biopsy exposed extracellular fungal
elements. A lung biopsy was performed and the tissue was cultured. After an
incubation period of six days at 35°C, blood agars yielded a yeast that
was identified as P. brasiliensis.
Therapy with an oral itraconazole was given as a dose of 100mg/day for six
months (6).
References
(1) Andrade, MG. Et al. 2007. Oral paracoccidioidomycosis:
a case without lung manifestations. 8(5):92-8.
(2) Bocca, Anamelia Lorenzetti. Et al. 2013. Paracoccidiomycosis: eco-epidemiology,
taxonomy, clinical and therapeutic issues. Future Microbiology (8): 1177.
(3)Catano, Juan C. Et al. 2013. Disseminated Paracoccidioidomycosis. The American Journal of
Tropical Medicine and Hygiene. 88(3): 407-408.
(4) Cavalcante, Ricardo de Souza. Et al. 2014. Comparison between Itraconazole and
Cotrimoxazole in the Treatment of Paracoccidioidomycosis. PLoS Neglected
Tropical Diseases. 8: e3348.
(5) Gow, Neil and Nino-Vega, Gustavo. 2002. Paracoccidioides brasiliensis – the
man-hater. Mycologist. Cambridge University Press.
(6) Manns, B.J. Et al. Paracoccidioidomycosis:
Case Report and Review. 1996. Clinical Infectious Diseases. 23:1026-32.
(7) Marques, Silvio Alencar. 2013. Paracoccidioidomycosis: epidemiological, clinical, diagnostic and
treatment up-dating. Brazilian Society of Dermatology. 88(5): 700-711.
(8) Motoyama, Andrea B. Et al. 2000. Molecular Identification of Paracoccidioides brasiliensis by PCR
Amplification of Ribosomal DNA. Journal of Clinical Microbiology. 38(8):
3106-3109.
(9) Munoz, Jose F. Et al. 2014. Genome Update of the Dimorphic Human Pathogenic Fungi Causing
Paracoccidioidomycosis. PLoS Neglected Tropical Diseases. 8(4): e2793.
(10) Mycology Online. 2016 Paracoccidioidomycosis. The University of Adelaide.
http://www.mycology.adelaide.edu.au/Mycoses/Dimorphic_systemic/Paracoccidioidomycosis/
(11) Negroni, Ricardo. 2014. Paracoccidioides brasiliensis (Paracoccidioidomycosis). Infectious
Disease & Antimicrobial Agents.
http://www.antimicrobe.org/f09.asp
(12) Paracoccidioides
Mold Species. 2015. Environmental
Hygienists. http://www.mold.ph/paracoccidioides.htm
(13) Revankar Sanjay G., and Sobel, Jack D. 2014. Paracoccidioidomycosis
(South American
Blastomycosis). Merck Sharpe and Dohme Corp. http://www.merckmanuals.com/professional/infectious-diseases/fungi/paracoccidioidomycosis
(14) Shikanai-Yasuda,
MA. Et al. 2006. Guidelines in paracoccidioidomycosis. Brazil Society
of Tropical Medicine. 39:297-310. http://cursoenarm.net/UPTODATE/contents/mobipreview.htm?24/38/25189
(15) Valera, Elvis Terci. Et al. 2008. Fungal infection by Paracoccidioides brasiliensis mimicking bone tumor.
Pediatric blood and cancer. 50(6):
1284-1286.
(16) Volk, Tom, and Mossman, Travis. 2005. Paracoccidioides brasiliensis, cause of
paracoccidioidomycosis, aka, South American Blastomycosis or Brazilian
Blastomycosis. University of Wisconsin-Lacrosse.
