Paracoccidiodes
Paracoccidiodes is a genus of dimorphic fungus, specifically represented by the species Paracoccidioides brasiliensis. This fungus is primarily found in humid soils of Central and South America, particularly in Brazil, and is a notable cause of paracoccidioidomycosis, a rare lung disease often referred to as South American blastomycosis. Paracoccidioides brasiliensis exhibits a unique thermal dimorphism, existing as a mold at lower temperatures and transforming into a yeast form at body temperature. Infection typically occurs through inhalation of conidia, with agricultural and forestry workers being the most at-risk populations.
The disease manifests with initial symptoms of mucocutaneous lesions, followed by respiratory issues, and can progress to more severe forms, including disseminated disease affecting the lymphatic system and skin. Diagnosis can be challenging due to a potential long incubation period. Treatment options vary, with itraconazole commonly used as a first-line medication, while sulfonamides remain a cost-effective alternative in Latin America. Understanding Paracoccidiodes is essential for recognizing its impact on public health in endemic regions and for developing effective management strategies.
Paracoccidiodes
- TRANSMISSION ROUTE: Inhalation
Definition
Paracoccidiodes is a genus of dimorphic fungus, with the single species brasiliensis. Infection with the fungus leads to paracoccidioidomycosis, a rare disease, primarily, of the lungs. The disease is also known as South American blastomycosis.
Natural Habitat and Features
Paracoccidiodes consists of one species, brasiliensis. Its natural habitat is Central America and South America, with Brazil the epicenter. The fungus resides in humid soil that is rich in proteins and in subtropical mountain forests. The fungus is the predominant cause of systemic fungal infection in humans in these areas and has also been isolated from fruit bats and armadillos, animals native to these areas.
Paracoccidiodes is a thermally dimorphic fungus. At lower temperatures, as in its natural habitat, it is a mold with many branching hyphae (filaments). At higher temperatures, as in the tissue of an infected host, it becomes a multibudding yeast. It is a mitosporic (asexual) fungus, with no known teleomorphic (sexual) stage.
Mold-to-yeast conversion must be demonstrated to confirm that brasiliensis is the fungal pathogen in an infected person. Brasiliensis grows as a mold at 77° Fahrenheit (25° Celsius) and as a yeast at 98.6° F (37° C). Mold colonies are filamentous, slow growing, leathery, flat to wrinkled, wooly, and cottony or smooth to velvety. Microscopic observation reveals transparent (hyaline) septate hyphae, that is, hyphae with partitioned cavities. Often, the hyphae are sterile and do not produce conidia, sporelike asexual reproductive bodies. If conidia are present, they are single-cell, oval, and truncated and with a broad base and round apex. They are located along the hyphae. Specialized spores, arthroconidia and chlamydospores, may also be observed. The colony obtains a diameter of 1 to 2 centimeters in two to three weeks. The front color is white cream, tan, or brown. The reverse color is yellowish brown to brown.
Mold-to-yeast conversion requires an enriched medium, such as brain heart infusion agar (or broth). Conversion occurs after ten to twenty days of incubation. The yeast colony is heaped, wrinkled, or folded and white. Microscopic observation reveals multiple buds (blastoconidia) surrounding thick-walled mother yeast cells, similar in shape to a ship pilot’s wheel. The buds are attached to the mother cell by a narrow neck portion. Before a bud detaches from the mother cell, secondary buds may form, producing short chains of yeast cells. When only single buds are observed, brasiliensis must be differentiated from Blastomyces dermatitidis. In contrast to the buds of brasiliensis, those of dermatitidis are broad-based.
Pathogenicity and Clinical Significance
Brasiliensis causes paracoccidioidomycosis. For the most part, cases of paracoccidioidomycosis are limited to areas where brasiliensis is native. Agricultural and forestry workers are particularly prone to infection. Isolated cases occur in persons, including immigrants and migrants, who have traveled to or from endemic regions. The infection is acquired through inhalation of conidia, which are transformed into yeast cells within alveolar macrophages in the lungs. Animal-to-animal and human-to-human transmission have not been demonstrated.
The development and degree of disease depends on the virility of the strain, the general health and immune status of the host, and, in adults, whether the host is a man or a woman. Men are fifteen times as likely as women to develop adult chronic infection. This appears to be so because fungal receptors bind to estrogen, the female sex hormone, but not to androgen, the male sex hormone. This inhibits conversion of the mold phase into the yeast phase.
Diagnosis of infection with brasiliensis is often difficult. Infection may not become apparent for several years after exposure. This suggests the possibility of a long latent period. For most infected persons, the first symptom of active disease is mucocutaneous lesions, especially of the mouth, nose, and throat, followed by respiratory symptoms, such as productive cough and shortness of breath.
In addition to causing primary pulmonary infection, brasiliensis can also cause acute primary, chronic primary, and disseminated disease. In disseminated disease, the reticuloendothelial system, lymph nodes, and skin and mucous membranes can become involved. Involvement of the reticuloendothelial system can lead to the suppression of the activity of phagocytic monocytes in the spleen, bone marrow, and lymph nodes. Aortitis, inflammation of the aorta, is also a risk. Immunocompromised persons are susceptible to the development of acute pulmonary and disseminated disease. The mortality rate from chronic infection with paracoccidioidomycosis among persons with acquired immunodeficiency syndrome (AIDS) ranges between 30 and 45 percent.
Drug Susceptibility
In vitro data on the susceptibility profile of brasiliensis are limited. A standardized in vitro susceptibility test has not been established. Testing methods that have been used have had varying results, making meaningful comparisons difficult. In general, relatively low minimum inhibitory concentrations (MICs) have been detected for amphotericin B and azoles, including ketoconazole, itraconazole, and fluconazole, when tested against the yeast phase of brasiliensis. Higher MICs have been reported for some isolates.
In the past, sulfonamides, amphotericin B, and ketoconazole were used to treat infections caused by brasiliensis. Sulfonamides, in particular trimethoprim/sulfamethoxazole (TMP) and sulfadiazine, are still used in Latin America because of their low costs. Paracoccidioidomycosis is the only systemic fungal infection that is treated with sulfonamides. Itraconazole has replaced ketoconazole because it is better tolerated and more effective. It has become the drug of first choice. Amphotericin B is reserved for persons with severe diseases who cannot tolerate oral medications.
Bibliography
Carlile, Michael J., Sarah C. Watkinson, and Graham W. Gooday. The Fungi. 2d ed. San Diego, Calif.: Academic Press, 2005.
Larone, Davise H. Medically Important Fungi: A Guide to Identification. 4th ed. Washington, D.C.: ASM Press, 2002.
"Paracoccidiodes Basics." Centers for Disease Control and Prevention (CDC), 24 Apr. 2024, www.cdc.gov/paracoccidioidomycosis/about/index.html. Accessed 4 Feb. 2025.
Restrepo, A., and A. M. Tobon. “ Paracoccidiodes brasiliensis.” In Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases, edited by Gerald L. Mandell, John F. Bennett, and Raphael Dolin. 7th ed. New York: Churchill Livingstone/Elsevier, 2010.
Webster, John, and Roland Weber. Introduction to Fungi. New York: Cambridge University Press, 2007.