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

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).

Figure 2. "Fungal lollipop" shape of Paracoccidioides (16)

The two species that cause paracoccidioidomycosis include Paracoccidioides brasiliensis and Paracoccidioides lutzii (2). P. lutzii was named as a tribute to the founder, Lutz (5). P. brasiliensis is dimorphic, which means it changes from mold to yeast at different temperatures. The macroscopic form is a mold at 25°C with slow-growth and it produces a white, tan, or brown, velvety colony with a diameter 1-2cm (Figure 3). At 37°C, the fungus is in a yeast form. This colony is white, wrinkled, and has a creamy texture (12). The microscopic form at 37°C, shows daughter cells attached to a mother cell by a steering wheel look-a-like and short chains of secondary cells are formed (Figure 1). At 27°C, a hyaline septate sterile hyphae is formed with an oval, unicellular, shortened, broad-based and rounded tip conidia along the hyphae (12). Colonization takes 20-30 days on an agar plate at room temperature (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).

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).

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).

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).

Figure 6.  Arrows reveal P. brasiliensis stained with Grocott’s methenamine
silver with 40X magnification (3).

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.