Paracoccidioidomycosis is a chronic, granulomatous, and progressive disease that mainly attacks the lungs, mucosa of the mouth and nose, and neighboring teguments, with frequent spread to the lymph nodes, adrenal glands, and other viscera. In fact it seems as though there is not anywhere in your body that is safe from the fungi once it gains entry either through the lungs or through traumatic implantation. Thus it's good to learn more about the disease and the fungus that causes it.
Paracoccidioides brasiliensis is the last of the truly pathogenic dimorphic pathogens to be Fungus of the Month. If you've been reading my pages, you know that the other three are Coccidioides immitis, Blastomyces dermatitidis, and Histoplasma capsulatum. Although most fungi need a person to be immunocompromised to cause disease, the four true human pathogens can cause disease in an immunocompetent host, as long as the inoculum size is sufficient. Some researchers believe that a single spore can cause disease, but most believe that a person must inhale dozens of spores to cause disease. These fungi are dimorphic (as are the opportunistic pathogens; Sporothrix schenckii and Penicillium marneffei), which means that at room temperature they form a mycelium (filaments), probably in the soil. The mycelium can form abundant spores, single at the tip of an unadorned conidiophore, as shown to the right. Someone with imagination called them "fungal lollipops." The hyphal form grows slowly in culture, colonizing a plate in 20-30 days at room temperature. Macroscopically the colonies are variable in color and texture, varying from ivory to brown and flat to wrinkled. Microscopic features include clamydospores and sometimes the formation of oval or round conidia. Under special culture-conditions aleurioconidia can be formed. Disease may begin when these spores are accidentally inhaled into the lungs, where they begin to grow and can morph into yeasts.
The transformation to yeast occurs when the temperature rises from room temperature to 37 C or higher. The whole organism undergoes DNA transcription changes that result in the formation of specific enzymes, redistribution of cell wall components, proteins, and cellular structuring. This altering of cell wall structure throws off the invaded host's defense mechanisms allowing the fungus to establish a foothold in the body for a longer period of time. Disease may be caused in the lungs, but more often the disease is resolved (cured of symptoms) in the lungs and from there is often disseminated to other parts of the body via the bloodstream..
The yeast forms at 37 C and grows much more rapidly, colonizing a plate in 5-10 days. Color varies with the agar used. Microscopic evaluation reveals round or oval yeast-like cells with singly or multiple budding daughter cells covering the surface. Multiple budding is the characteristic form of the fungi and is used to diagnose the disease when found in biopsy of tissues. Change from yeast phase to hyphal phase is also necessary to properly diagnose the disease.
Paracoccidioidomycosis was discovered in 1908 by Lutz, who was able to culture the fungus from a lesion and isolate it. During the early years it was often mistaken for Coccidioides immitis. In fact the prefix "para-" in Paracoccidioides means "similar to," so this name means "like Coccidioides. If you've been keeping up with my pages (or you know a bit of Latin and Greek) you know that the suffix "-oides" means "similar to." Coccidioides is named after a protozoan parasite of chickens called Coccidia. Thus Paracoccidioides means "a fungus that's like another fungus that's like the protozoan Coccidia. And taxonomists wonder why people roll their eyes at the fungal names they come up with. Incidentally the 22-letter word "paracoccidioidomycosis" is the longest word I make my medical mycology students learn how to spell
The disease (and the fungus) was named (and renamed) by mycologists many time as it was discovered (and rediscovered) in other areas. This disease is also called South American Blastomycosis. Blastomycosis literally means "yeast disease," but it is specifically applied to diseases caused by Blastomyces dermatitidis. The symptoms of the two diseases can be similar, and the endemic regions can sometimes overlap, so the two can be easily confused. In addition their aleurioconidial state, resembling a lollipop on a stick, is also similar. However, they can distinguished in their yeast phase (in the body or in culture) by their budding pattern. Blastomyces normally has a single bud with a broad base, while Paracoccidioides has multiple narrow-based buds, resmbling a famous cartoon mouse or a pilot wheel (think Steamboat Willie...). All that being said, there are some mycologists who place Paracoccidioides brasiliensis in the genus Blastomyces because of their similarities.
Skin test studies and recovery of the fungus indicates that its natural niche is in soil in humid mountain forests-more than 8000 cases are recorded in the literature, which gives a good picture of the distribution of the disease in Central and South America. Oddly enough, the disease is rare in the rain forests themselves. The symptoms of paracoccidioidomycosis are varied, and their severity may be determined by the number of spores inhaled, the virulence of that particular strain of the pathogen, and the competency of the immune system of the host. Most cases seem to be in males 20-50 years old in rural areas. Although the gender ratio in skin tests is 1:1, clinical disease is 7:1- 70:1 male:female, which is similar to other systemic mycoses. This may have to do with exposure, but at least some part of it must be related to hormonal differences. The disease, which thrives in hot climates, can be fatal if not treated.
Found from Mexico to Argentina, paracoccidioidomycosis is the most commonly encountered mycosis of Latin America . Cases reported outside the endemic areas have a history of residence in the endemic areas. There are approximately ten million people in Brazil who are infected with the fungus. Without proper treatment over time many of the people's lungs will be destroyed and the fungus will disseminate into the body causing further complications leading to death.
I hope you learned something about a deadly fungal disease.
This month's co-author is Travis Mossman (shown to the left), one of my students in medical mycology and advanced mycology. Thanks to Dr. John Rippon, Professor Emeritus from the University of Chicago, for providing most of the pictures on this page. In fact, I just thanked him in person as I am writing this on his patio, overlooking his pool and palms in Florida. Dr. Rippon is also the Guest Pronouncer for this month's fungus.
If you have anything to add, or if you have corrections, comments, or recommendations for future FotM's (or maybe you'd like to be co-author of a FotM?), please write to me at firstname.lastname@example.org
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