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Semin Respir Crit Care Med 2011; 32(6): 764-774
DOI: 10.1055/s-0031-1295724
© Thieme Medical Publishers

Pulmonary Paracoccidioidomycosis

Flavio Queiroz-Telles1 , Dante L. Escuissato2
  • 1Division of Infectious Diseases, Department of Public Health, Federal University of Parana, Curitiba–Parana, Brazil
  • 2Division of Radiology, Department of Internal Medicine, Federal University of Parana, Curitiba–Parana, Brazil
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Publication History

Publication Date:
13 December 2011 (online)

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ABSTRACT

Paracoccidioidomycosis is a subacute or chronic systemic mycosis caused by Paracoccidioides brasiliensis, a soil saprophyte and thermally dimorphic fungus. The disease occurs mainly in rural workers in Latin America and is the most frequent endemic systemic mycosis in many countries of South America, where almost 10 million people are believed to be infected. Paracoccidioidomycosis should be regarded as a disease of travelers outside the endemic area. The primary pulmonary infection is subclinical in most cases, and individuals may remain infected throughout life without ever developing clinical signs. A small proportion of patients present with clinical disease. The lungs are frequently involved, and the pulmonary clinical manifestations must be differentiated from many other infectious and noninfectious conditions. Diagnosis should be based on epidemiological, clinical, and microbiological data. Effective treatment regimens are available to control the fungal infection, but most patients develop fibrotic sequelae that may severely hamper respiratory and adrenal function and the patient’s well-being.

KEYWORDS

Paracoccidioidomycosis - South American blastomycosis - Paracoccidioides brasiliensis, systemic mycosis

REFERENCES

  • 1 Lutz A. Uma mycose pseudococcidica localizada na boca e observada no Brasil: contribuição ao conhecimento das hyphoblastomycoses Americanas.  Bras Med. 1908;  22 141-144
    Google Scholar
  • 2 Colombo A L, Tobón A, Restrepo A, Queiroz-Telles F, Nucci M. Epidemiology of endemic systemic fungal infections in Latin America.  Med Mycol. 2011;  49 (8) 785-798 Epub ahead of print
    Google Scholar
  • 3 Wanke B, Londero A T. Epidemiology and paracoccidioidomycosis infection. In: Franco M, da Silva Lacaz C, Restrepo-Moreno A, Del Negro G, eds. Paracoccidiodomycosis. Boca Raton, FL: CRC Press; 1994: 109-117
    Google Scholar
  • 4 Brummer E, Castaneda E, Restrepo A. Paracoccidioidomycosis: an update.  Clin Microbiol Rev. 1993;  6 (2) 89-117
    Google Scholar
  • 5 Colombo A, Queiroz-Telles F. Paracoccidioidomycosis. In: Mandell G D, Kauffman C A, eds. Atlas of Infectious Diseases. 2nd ed. Philadelphia: Current Medicine; 2007: 53-70
    Google Scholar
  • 6 Chu J H, Feudtner C, Heydon K, Walsh T J, Zaoutis T E. Hospitalizations for endemic mycoses: a population-based national study.  Clin Infect Dis. 2006;  42 (6) 822-825
    Google Scholar
  • 7 Blotta M H, Mamoni R L, Oliveira S J et al.. Endemic regions of paracoccidioidomycosis in Brazil: a clinical and epidemiologic study of 584 cases in the southeast region.  Am J Trop Med Hyg. 1999;  61 (3) 390-394
    Google Scholar
  • 8 Paniago AMM, Aguiar JIA, Aguiar E S et al.. Paracoccidioidomycosis: a clinical and epidemiological study of 422 cases observed in Mato Grosso do Sul [in Portuguese].  Rev Soc Bras Med Trop. 2003;  36 (4) 455-459
    Google Scholar
  • 9 Nucci M, Colombo A L, Queiroz-Telles F. Paracoccidioidomycosis.  Curr Fungal Infect Rep. 2009;  3 15-20
    Google Scholar
  • 10 Negroni R. Paracoccidioidomycosis (South American blastomycosis, Lutz’s mycosis).  Int J Dermatol. 1993;  32 (12) 847-859
    Google Scholar
  • 11 Restrepo A, Robledo M, Giraldo R et al.. The gamut of paracoccidioidomycosis.  Am J Med. 1976;  61 (1) 33-42
    Google Scholar
  • 12 Londero A T, Severo L C. The gamut of progressive pulmonary paracoccidioidomycosis.  Mycopathologia. 1981;  75 (2) 65-74
    Google Scholar
  • 13 Restrepo A, Benard G, de Castro C C, Agudelo C A, Tobón A M. Pulmonary paracoccidioidomycosis.  Semin Respir Crit Care Med. 2008;  29 (2) 182-197
    Google Scholar
  • 14 Graybill J R, Anstead G M, Queiroz-Telles F. The diagnosis of endemic Mycoses. In: Maertens J A, Marr K A, eds. Diagnosis of Fungal Infections. New York, NY: Informa Healthcare USA; 2007: 291-353
    Google Scholar
  • 15 San-Blas G, Niño-Vega G, Iturriaga T. Paracoccidioides brasiliensis and paracoccidioidomycosis: molecular approaches to morphogenesis, diagnosis, epidemiology, taxonomy and genetics.  Med Mycol. 2002;  40 (3) 225-242
    Google Scholar
  • 16 Bialek R, Ibricevic A, Fothergill A, Begerow D. Small subunit ribosomal DNA sequence shows Paracoccidioides brasiliensis closely related to Blastomyces dermatitidis.  J Clin Microbiol. 2000;  38 (9) 3190-3193
    Google Scholar
  • 17 Kasuga T, White T J, Koenig G et al.. Phylogeography of the fungal pathogen Histoplasma capsulatum.  Mol Ecol. 2003;  12 (12) 3383-3401
    Google Scholar
  • 18 Bagagli E, Theodoro R C, Bosco SMG, McEwen J G. Paracoccidioides brasiliensis: phylogenetic and ecological aspects.  Mycopathologia. 2008;  165 (4-5) 197-207
    Google Scholar
  • 19 Theodoro R C, Bagagli E, Oliveira C. Phylogenetic analysis of PRP8 intein in Paracoccidioides brasiliensis species complex.  Fungal Genet Biol. 2008;  45 (9) 1284-1291
    Google Scholar
  • 20 Untereiner W A, Scott J A, Naveau F A, Sigler L, Bachewich J, Angus A. The Ajellomycetaceae, a new family of vertebrate-associated Onygenales.  Mycologia. 2004;  96 (4) 812-821
    Google Scholar
  • 21 Bagagli E, Bosco SMG, Theodoro R C, Franco M. Phylogenetic and evolutionary aspects of Paracoccidioides brasiliensis reveal a long coexistence with animal hosts that explain several biological features of the pathogen.  Infect Genet Evol. 2006;  6 (5) 344-351
    Google Scholar
  • 22 Queiroz-Telles F. Paracoccidioides brasiliensis: ultrastructural findings. In: Franco M, ed. Paracoccidioidomycosis. Boca Raton, FL: CRC Press; 1994: 27-47
    Google Scholar
  • 23 San-Blas G, Niño-Vega G, Iturriaga T. Paracoccidioides brasiliensis and paracoccidioidomycosis: molecular approaches to morphogenesis, diagnosis, epidemiology, taxonomy and genetics.  Med Mycol. 2002;  40 (3) 225-242
    Google Scholar
  • 24 Negroni P. The Paracoccidioides brasiliensis lives saprophytically in the soil of Argentina [in Spanish].  Prensa Med Argent. 1966;  53 (39) 2381-2382
    Google Scholar
  • 25 Restrepo A. The ecology of Paracoccidioides brasiliensis: a puzzle still unsolved.  Sabouraudia. 1985;  23 (5) 323-334
    Google Scholar
  • 26 Ferreira M S, Freitas L H, Lacaz Cda S et al.. Isolation and characterization of a Paracoccidioides brasiliensis strain from a dogfood probably contaminated with soil in Uberlandia, Brazil.  J Med Vet Mycol. 1990;  28 (3) 253-256
    Google Scholar
  • 27 Silva-Vergara M L, Martınez R, Chadu A, Madeira M, Freitas-Silva G, Leite Maffei C M. Isolation of a Paracoccidioides brasiliensis strain from the soil of a coffee plantation in Ibiá, State of Minas Gerais, Brazil.  Med Mycol. 1998;  36 (1) 37-42
    Google Scholar
  • 28 Bagagli E, Sano A, Coelho KIR et al.. Isolation of Paracoccidioides brasiliensis from armadillos (Dasypus noveminctus) captured in an endemic area of paracoccidioidomycosis.  Am J Trop Med Hyg. 1998;  58 (4) 505-512
    Google Scholar
  • 29 Franco M, Bagagli E, Scapolio S, da Silva Lacaz C. A critical analysis of isolation of Paracoccidioides brasiliensis from soil.  Med Mycol. 2000;  38 (3) 185-191
    Google Scholar
  • 30 Bagagli E, Franco M, Bosco SdeM, Hebeler-Barbosa F, Trinca L A, Montenegro M R. High frequency of Paracoccidioides brasiliensis infection in armadillos (Dasypus novemcinctus): an ecological study.  Med Mycol. 2003;  41 (3) 217-223
    Google Scholar
  • 31 Mok W Y, Netto C F. Paracoccidioidin and histoplasmin sensitivity in Coari (state of Amazonas), Brazil.  Am J Trop Med Hyg. 1978;  27 (4) 808-814
    Google Scholar
  • 32 de Andrade JAF, de Andrade T M, Lacaz CdaS et al.. Survey on paracoccidioidin in a population of Bahia (Brazil)[in Portuguese].  Rev Inst Med Trop Sao Paulo. 1984;  26 (1) 1-6
    Google Scholar
  • 33 Hay R J, Rose P, Jones T R. Paracoccidioidin sensitization in Guyana—a preliminary skin test survey in hospitalized patients and laboratory workers.  Trans R Soc Trop Med Hyg. 1987;  81 (1) 46-48
    Google Scholar
  • 34 Bittencourt J I, de Oliveira R M, Coutinho Z F. Paracoccidioidomycosis mortality in the State of Paraná, Brazil, 1980/1998.  Cad Saude Publica. 2005;  21 (6) 1856-1864
    Google Scholar
  • 35 Coutinho Z F, Silva D, Lazera M et al.. Paracoccidioidomycosis mortality in Brazil (1980-1995).  Cad Saude Publica. 2002;  18 (5) 1441-1454
    Google Scholar
  • 36 Ono M A, Itano E N, Mizuno L T, Mizuno E H, Camargo Z P. Inhibition of Paracoccidioides brasiliensis by pesticides: is this a partial explanation for the difficulty in isolating this fungus from the soil?.  Med Mycol. 2002;  40 (5) 493-499
    Google Scholar
  • 37 Queiroz-Telles F. Influence of alternating coffee and sugar cane agriculture in the incidence of paracoccidioidomycosis in Brazil.  Biomedica. 2008;  28 (Suppl 1) 129
    Google Scholar
  • 38 Restrepo A, Salazar M E, Cano L E, Stover E P, Feldman D, Stevens D A. Estrogens inhibit mycelium-to-yeast transformation in the fungus Paracoccidioides brasiliensis: implications for resistance of females to paracoccidioidomycosis.  Infect Immun. 1984;  46 (2) 346-353
    Google Scholar
  • 39 Aristizabal B H, Clemons K V, Stevens D A, Restrepo A. Morphological transition of Paracoccidioides brasiliensis conidia to yeast cells: in vivo inhibition in females.  Infect Immun. 1998;  66 (11) 5587-5591
    Google Scholar
  • 40 dos Santos W A, da Silva B M, Passos E D, Zandonade E, Falqueto A. Association between smoking and paracoccidioidomycosis: a case-control study in the State of Espírito Santo, Brazil [in Portuguese].  Cad Saude Publica. 2003;  19 (1) 245-253
    Google Scholar
  • 41 Paniago A M, de Freitas A C, Aguiar E S et al.. Paracoccidioidomycosis in patients with human immunodeficiency virus: review of 12 cases observed in an endemic region in Brazil.  J Infect. 2005;  51 (3) 248-252
    Google Scholar
  • 42 Shikanai-Yasuda M A, Conceição Y M, Kono A, Rivitti E, Campos A F, Campos S V. Neoplasia and paracoccidioidomycosis.  Mycopathologia. 2008;  165 (4-5) 303-312
    Google Scholar
  • 43 Zavascki A P, Bienardt J C, Severo L C. Paracoccidoidomycosis in organ transplant: case report.  Rev Inst Med Trop Sao Paulo. 2004;  46 (5) 279-281
    Google Scholar
  • 44 Ricci G, Mota F T, Wakamatsu A, Serafim R C, Borra R C, Franco M. Canine paracoccidioidomycosis.  Med Mycol. 2004;  42 (4) 379-383
    Google Scholar
  • 45 Benard G. An overview of the immunopathology of human paracoccidioidomycosis.  Mycopathologia. 2008;  165 (4-5) 209-221
    Google Scholar
  • 46 Goldani L Z, Sugar A M. Paracoccidioidomycosis and AIDS: an overview.  Clin Infect Dis. 1995;  21 (5) 1275-1281
    Google Scholar
  • 47 Paniago A M, de Freitas A C, Aguiar E S et al.. Paracoccidioidomycosis in patients with human immunodeficiency virus: review of 12 cases observed in an endemic region in Brazil.  J Infect. 2005;  51 (3) 248-252
    Google Scholar
  • 48 Franco M, Mendes R P, Moscardi-Bacchi M et al.. Paracoccidioidomycosis. In: Hay R J, ed. Clinical Tropical Medicine and Communicable Diseases. Ist ed. London: Bailliere Tindall; 1989: 185-220
    Google Scholar
  • 49 Quagliato Júnior R, Grangeia TdeA, Massucio R A, De Capitani E M, Rezende SdeM, Balthazar A B. Association between paracoccidioidomycosis and tuberculosis: reality and misdiagnosis.  J Bras Pneumol. 2007;  33 (3) 295-300
    Google Scholar
  • 50 Funari M, Kavakama J, Shikanai-Yasuda M A et al.. Chronic pulmonary paracoccidioidomycosis (South American blastomycosis): high-resolution CT findings in 41 patients.  AJR Am J Roentgenol. 1999;  173 (1) 59-64
    Google Scholar
  • 51 Gomes E, Wingeter M A, Svidzinski T I. Clinical-radiological dissociation in lung manifestations of paracoccidioidomycosis [in Portuguese].  Rev Soc Bras Med Trop. 2008;  41 (5) 454-458
    Google Scholar
  • 52 Funari M, Kavakama J, Shikanai-Yasuda M A et al.. Chronic pulmonary paracoccidioidomycosis (South American blastomycosis): high-resolution CT findings in 41 patients.  AJR Am J Roentgenol. 1999;  173 (1) 59-64
    Google Scholar
  • 53 Souza Jr A S, Gasparetto E L, Davaus T, Escuissato D L, Marchiori E. High-resolution CT findings of 77 patients with untreated pulmonary paracoccidioidomycosis.  AJR Am J Roentgenol. 2006;  187 (5) 1248-1252
    Google Scholar
  • 54 Marchiori E, Valiante P M, Mano C M et al.. Paracoccidioidomycosis: high-resolution computed tomography-pathologic correlation.  Eur J Radiol. 2011;  77 (1) 80-84
    Google Scholar
  • 55 Gasparetto E L, Escuissato D L, Davaus T et al.. Reversed halo sign in pulmonary paracoccidioidomycosis.  AJR Am J Roentgenol. 2005;  184 1932-1934
    Google Scholar
  • 56 Tobón A M, Agudelo C A, Osorio M L et al.. Residual pulmonary abnormalities in adult patients with chronic paracoccidioidomycosis: prolonged follow-up after itraconazole therapy.  Clin Infect Dis. 2003;  37 (7) 898-904
    Google Scholar
  • 57 Cano L E, Restrepo A. Predictive value of serologic tests in the diagnosis and follow-up of patients with paracoccidioidomycosis.  Rev Inst Med Trop Sao Paulo. 1987;  29 (5) 276-283
    Google Scholar
  • 58 de Camargo Z P, de Franco M F. Current knowledge on pathogenesis and immunodiagnosis of paracoccidioidomycosis.  Rev Iberoam Micol. 2000;  17 (2) 41-48
    Google Scholar
  • 59 Wheat L J, Garringer T, Brizendine E, Connolly P. Diagnosis of histoplasmosis by antigen detection based upon experience at the histoplasmosis reference laboratory.  Diagn Microbiol Infect Dis. 2002;  43 (1) 29-37
    Google Scholar
  • 60 Gómez B L, Figueroa J I, Hamilton A J et al.. Antigenemia in patients with paracoccidioidomycosis: detection of the 87-kilodalton determinant during and after antifungal therapy.  J Clin Microbiol. 1998;  36 (11) 3309-3316
    Google Scholar
  • 61 Marques da Silva S H, Colombo A L, Blotta M H, Lopes J D, Queiroz-Telles F, Pires de Camargo Z. Detection of circulating gp43 antigen in serum, cerebrospinal fluid, and bronchoalveolar lavage fluid of patients with paracoccidioidomycosis.  J Clin Microbiol. 2003;  41 (8) 3675-3680
    Google Scholar
  • 62 Marques da Silva S H, Queiroz-Telles F, Colombo A L et al.. Monitoring gp43 antigenemia in Paracoccidioidomycosis patients during therapy.  J Clin Microbiol. 2004;  42 2419-2424
    Google Scholar
  • 63 Tuder R M, el Ibrahim R, Godoy C E, De Brito T. Pathology of the human pulmonary paracoccidioidomycosis.  Mycopathologia. 1985;  92 (3) 179-188
    Google Scholar
  • 64 Stevens D A, Vo P T. Synergistic interaction of trimethoprim and sulfamethoxazole on Paracoccidioides brasiliensis.  Antimicrob Agents Chemother. 1982;  21 (5) 852-854
    Google Scholar
  • 65 Dillon N L, Sampaio S A, Habermann M C et al.. Delayed results of treatment of paracoccidioidomycosis with amphotericin B plus sulfamides versus amphotericin B alone.  Rev Inst Med Trop Sao Paulo. 1986;  28 (4) 263-266
    Google Scholar
  • 66 Diaz M, Negroni R, Montero-Gei F Pan-American Study Group et al. A Pan-American 5-year study of fluconazole therapy for deep mycoses in the immunocompetent host.  Clin Infect Dis. 1992;  14 (Suppl 1) S68-S76
    Google Scholar
  • 67 Dietze R, Fowler Jr V G, Steiner T S, Pecanha P M, Corey G R. Failure of amphotericin B colloidal dispersion in the treatment of paracoccidioidomycosis.  Am J Trop Med Hyg. 1999;  60 (5) 837-839
    Google Scholar
  • 68 Naranjo M S, Trujillo M, Munera M I, Restrepo P, Gomez I, Restrepo A. Treatment of paracoccidioidomycosis with itraconazole.  J Med Vet Mycol. 1990;  28 (1) 67-76
    Google Scholar
  • 69 Shikanai-Yasuda M A, Benard G, Higaki Y et al.. Randomized trial with itraconazole, ketoconazole and sulfadiazine in paracoccidioidomycosis.  Med Mycol. 2002;  40 (4) 411-417
    Google Scholar
  • 70 Queiroz-Telles F, Goldani L Z, Schlamm H T, Goodrich J M, Espinel-Ingroff A, Shikanai-Yasuda M A. An open-label comparative pilot study of oral voriconazole and itraconazole for long-term treatment of paracoccidioidomycosis.  Clin Infect Dis. 2007;  45 (11) 1462-1469
    Google Scholar
  • 71 Lutsar I, Roffey S, Troke P. Voriconazole concentrations in the cerebrospinal fluid and brain tissue of guinea pigs and immunocompromised patients.  Clin Infect Dis. 2003;  37 (5) 728-732
    Google Scholar
  • 72 Tobon A, Agudelo C A, Restrepo A. Posaconazole for the treatment of paracoccidioidomycosis: first clinical results.  Biomedica. 2008;  28 (Suppl 1) 205
    Google Scholar
  • 73 Moraes C S, Queiroz-Telles F, Marchiori E, Escuissato D L. Review of lung radiographic findings during treatment of patients with chronic paracoccidioidomycosis.  Radiol Bras. 2006;  39 175-179
    Google Scholar
  • 74 Naranjo T W, Lopera D E, Diaz-Granados L R, Duque J J, Restrepo A M, Cano L E. Combined itraconazole-pentoxifylline treatment promptly reduces lung fibrosis induced by chronic pulmonary paracoccidioidomycosis in mice.  Pulm Pharmacol Ther. 2011;  24 (1) 81-91
    Google Scholar
  • 75 Marques A F, da Silva M B, Juliano M A, Travassos L R, Taborda C P. Peptide immunization as an adjuvant to chemotherapy in mice challenged intratracheally with virulent yeast cells of Paracoccidioides brasiliensis.  Antimicrob Agents Chemother. 2006;  50 (8) 2814-2819
    Google Scholar

Flavio Queiroz-TellesM.D. Ph.D. 

Department of Public Health, Hospital de Clinicas, Federal University of Parana, Rua General Carneiro

181, Curitiba–PR–Brazil 80060-900

Email: queiroz.telles@uol.com.br

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