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Vol. 14. Issue S2.
Pages 145-158 (December 2010)
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Vol. 14. Issue S2.
Pages 145-158 (December 2010)
Open Access
Detección e identificación de Histoplasma capsulatum por el laboratorio: de los métodos convencionales a las pruebas moleculares
Detection and identification of the fungal pathogen Histoplasma capsulatum: from conventional to molecular methods
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César O. Muñoz1, Luz E. Cano1, Angel González1,
Corresponding author
agonzalezm@cib.org.co

Correspondencia: Grupo de Micología Médica y Experimental, Corporación para Investigaciones Biológicas (CIB), Carrera 72A # 78 B 141, Medellín, Colombia. Tel.: +057-4-441 08 55 ext 206; Fax: +057-4-441 55 14.
1 Grupo de Micología Médica y Experimental, Corporación para Investigaciones Biológicas (CIB), Escuela de Microbiología, Universidad de Antioquia, y Escuela de la Salud, Universidad Pontificia Bolivariana (UPB), Medellín, Colombia
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Resumen

La histoplasmosis, micosis sistémica y endémica en una amplia zona de las Américas, es causada por el hongo dimórfico Histoplasma capsulatum. Tradicionalmente, el diagnóstico de esta entidad se realiza por métodos microbiológicos directos y biopsias que emplean una variedad de coloraciones especiales tales como Wright, Giemsa y plata metenamina, entre otras, así como por cultivo; este último representa el estándar de oro. Se emplean, igualmente, métodos indirectos que incluyen la detección de anticuerpos y antígenos. Los valores de sensibilidad y especificidad en ambos métodos son variables, y los resultados dependen, a su vez, de la forma clínica de la enfermedad que presente el paciente y de su estado inmune.

Recientemente, la biología molecular ha permitido introducir nuevas herramientas que han sido utilizadas para la detección e identificación de H. capsulatum, una de ellas es la PCR anidada que se caracteriza por sus altos niveles de sensibilidad y especificidad. De igual forma, estas técnicas moleculares han permitido realizar análisis evolutivos, estudios de diversidad genética y un sinnúmero de estudios de epidemiología molecular, a partir de los cuales se ha logrado recopilar información valiosa sobre la variabilidad genética de este microorganismo.

En esta revisión se describen los métodos de laboratorio convencionales y las técnicas moleculares más empleadas para el diagnóstico de la histoplasmosis; así como también algunas de sus aplicaciones en la epidemiología y biología molecular de este hongo.

Palabras claves:
Histoplasma capsulatum
Histoplasmosis
Diagnóstico
Técnicas convencionales
Diagnóstico molecular
Abstract

Histoplasma capsulatum is the causative agent of histoplasmosis, a systemic and endemic mycosis widely distributed in the Americas. Diagnosis of histoplasmosis is traditionally accomplished by means of direct preparations and biopsies stained by especial methods, as well as by isolation of fungus in culture; the latter is considered the gold standard. Indirect methods, including immunological tests to detect antibodies and/or antigens, are also valuable; both direct and indirect methods present sensitivity and specificity ranges that vary depending on the clinical form of the disease and the immune status of the host. Recently, molecular biology has allowed implementing new tools to detect and identify H. capsulatum, and several molecular tests, such as nested-PCR, are being used for the diagnosis of histoplasmosis, and so provide high sensitivity and specificity values. In addition, these molecular techniques have made it possible to perform evolution analysis, genetic diversity research, and molecular epidemiology, thus compiling valuable information on the genetic variability of this microorganism.

In this review, the conventional and molecular methods employed for the diagnosis of histoplasmosis have been described, as have some of the applications of these molecular techniques to this fungal pathogen's epidemiology and molecular biology.

Key words:
Histoplasma capsulatum
Histoplasmosis
Diagnosis
Conventional techniques
Molecular diagnosis
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Referencias
[1.]
M.L. Taylor, A. Pérez-Mejía, J.K. Yamamoto-Furusho, J. Granados.
Immunologic, genetic and social human risk factors associated to histoplasmosis: Studies in the State of Guerrero, Mexico.
Mycopathologia, 138 (1997), pp. 137-141
[2.]
M.L. Taylor, M.R. Reyes-Montes, M.A. Martínez-Rivera, G. Rodríguez-Arellanes, E. Duarte-Escalante.
Histoplasmosis en México. Aportaciones inmunológicas y moleculares sobre su epidemiología.
Ciencia y Desarrollo, 23 (1997), pp. 58-63
[3.]
L.J. Wheat, C.A. Kauffman.
Histoplasmosis.
Infect Dis Clin N Am, 17 (2003), pp. 1-19
[4.]
E. Adderson.
Histoplasmosis.
J Pediatr Infect Dis, 25 (2006), pp. 73-74
[5.]
C.E. López.
Dimorfismo y patogenia de Histoplasma capsulatum.
Rev Argent Microbiol, 38 (2006), pp. 235-242
[6.]
D.M. Retallack, J.P. Woods.
Molecular epidemiology, pathogenesis, and genetics of the dimorphic fungus Histoplasma capsulatum.
Microbes Infect, 1 (1999), pp. 817-825
[7.]
L.G. Eissenberg, W.E. Goldman.
The interp lay between Histoplasma capsulatum and its host cells.
Bailliere's Clin Infect Dis., 1 (1994), pp. 265-283
[8.]
M.L. Taylor, J. Granados, C. Toriello.
Biological and sociocultural approaches of histoplasmosis in the State of Guerrero, Mexico.
Mycoses, 39 (1996), pp. 375-379
[9.]
M.L. Taylor, C.B. Chávez-Tapia, R. Vargas-Yáñez, G. Rodríguez-Arellanes, G.R. Peña-Sandoval, C. Toriello, et al.
Environmental conditions favoring bat infection with Histoplasma capsulatum in Mexican shelters.
Am J Trop Med Hyg, 61 (1999), pp. 914-919
[10.]
C.A. Kauffman, Histoplasmosis:.
a clinical and laboratory update.
Clin Microbiol Rev, 20 (2007), pp. 115-132
[11.]
E.W. Chick, S.B. Compton, H.T. Pass, B. Mackey, C. Hernandez, J.R.E. Austin, et al.
Hitchcok's birds, or the increased rate of exposure to Histoplasma from blackbird roost sites.
Chest., 80 (1981), pp. 434-438
[12.]
M.L. Taylor, C.B. Chávez-Tapia, M.R. Reyes-Montes.
Molecular typing of Histoplasma capsulatum isolated from infected bats, captured in Mexico.
Fungal Genet Biol, 30 (2000), pp. 207-212
[13.]
M.L. Taylor, C.B. Chavez-Tapias, A. Rojas-Martinez, M. del Rocio Reyes-Montes, M.B. del Valle, G. Zúñiga.
Geographical distribution of genetic polymorphism of the pathogen Histoplasma capsulatum isolated from infected bats, captured in a central zone of Mexico.
FEMS Immunol Med Microbiol, 45 (2005), pp. 451-458
[14.]
T. Kasuga, T.J. White, G. Koenig, J. McEwen, A. Restrepo, E. Castañeda, et al.
Phylogeography of the fungal pathogen Histoplasma capsulatum.
Mol Ecol, 12 (2003), pp. 3383-3401
[15.]
A. Restrepo.
Histoplasmosis.
Enfermedades Infecciosas, 6a edición, pp. 316-326
[16.]
C.A. Kauffman.
Histoplasmosis.
Clin Chest Med, 30 (2009), pp. 217-225
[17.]
J.L. Wheat.
Histoplasmosis: a reviews for clinicians from nonendemic areas.
[18.]
A.M. Tobón, C.A. Agudelo, D.S. Rosero, J.E. Ochoa, C. Bedout, A. Zuluaga, et al.
Disseminated histoplasmosis: a comparative study between patients with acquired immunodeficiency syndrome and non-human immunodeficiency virus-infected individuals.
Am J Trop Med Hyg, 73 (2005), pp. 576-582
[19.]
A. Doughan.
Disseminated histoplasmosis: case report and brief review.
Travel Med Infect Dis, 4 (2006), pp. 332-335
[20.]
J.A. Casotti, T.Q. Motta, C.U. Ferreira Júnior, C. Cerutti Junior.
Disseminated histoplasmosis in HIV positive patients in Espitito Santo state, Brazil: a clinical-laboratory study of 12 cases (1999-2001).
Braz J Infect Dis, 10 (2006), pp. 327-330
[21.]
S.A. Joshi, A.S. Kagal, R.S. Bharadwaj, S.S. Kulkarni, M.V. Jadhav.
Disseminated histoplasmosis.
Indian J Med Microbiol, 24 (2006), pp. 297-298
[22.]
E.F. Daher, G.B. Silva Jr., F.A. Barros, C.F. Takeda, R.M. Mota, M.T. Ferreira, et al.
Clinical and laboratory features of disseminated histoplasmosis in HIV patients from Brazil.
Trop Med Int Health, 12 (2007), pp. 1108-1115
[23.]
A.W. Yen, M.C. Henderson.
Disseminated histoplasmosis.
J Hosp Med, 2 (2007), pp. 46
[24.]
D.J. Mora, C.T. Barbosa Dos Santos, M.L. Silva-Vergara.
Disseminated histoplasmosis in acquired immunodeficiency syndrome patients in Uberaba, MG, Brazil.
[25.]
L.J. Wheat.
Histoplasmosis in the acquired immunodeficiency syndrome.
Curr Top Med Mycol, 7 (1996), pp. 7-18
[26.]
L.J. Wheat, G. Sarosi, D. McKinsey, R. Hamill, R. Bradsher, P. Johnson, et al.
Practice guidelines for the management of patients with Histoplasmosis.
Clin Inect Dis, 30 (2000), pp. 688-695
[27.]
A. Ordoñez, A. Tobón, M. Arango, A. Tabares, C. De Bedout, B. Gómez, et al.
Brotes de histoplasmosis registrados en el área andina colombiana.
Biomédica, 17 (1997), pp. 105-111
[28.]
M. Arango, E. Castañeda, C. De Bedout, C. Agudelo, C.I. Agudelo, A. Tobón, et al.
Histoplasmosis: resultados de la encuesta nacional 1992-2008.
Infectio, 14 (2010), pp. 1-92
[29.]
L.J. Wheat.
Current diagnosis of histoplasmosis.
Trends in Microbiol, 11 (2003), pp. 488-494
[30.]
R.M. Zancope-Oliveira, P.M. Silva, M. Medeiros.
Genetic diversity of Histoplasma capsulatum strains in Brazil.
FEMS Immunol Med Microbiol, 45 (2005), pp. 443-449
[31.]
E.C. Canteros, M.F. Zuiani, V. Ritacco, D.E. Perrotta, M.R. Reyes-Montes, J. Granados, et al.
Electrophoresis karyotype and chromosome-length polymorphism of Histoplasma capsulatum clinical isolates from Latin America.
FEMS Immunol Med Microbiol, 45 (2005), pp. 423-428
[32.]
M.L. Taylor, G.M. Ruiz-Palacios, M.R. Reyes-Montes, G. Rodriguez-Arellanes, L.E. Carreto-Binaghi-Carreto, Duarte-Escalante, et al.
Identification of the infectious source of an unusual outbreak of histoplasmosis, in a hotel Acapulco, state of Guerrero, Mexico.
FEMS Immunol Med Microbiol, 45 (2005), pp. 435-441
[33.]
M. Ieven, H. Goosseens.
Relevance of nucleic acid amplification techniques for diagnosis of respiratory tract infections in the clinical laboratory.
Clin Microbiol Rev, 10 (1997), pp. 242-256
[34.]
M.D. Lindsley, S.F. Hurst, N.J. Iqbal, C.J. Morrison.
Rapid identification of dimorphic and yeast-like fungal pathogens using specific DNA probes.
J Clin Microbiol, 39 (2001), pp. 3305-3311
[35.]
P. Flori, B. Bellete, F. Durand, H. Raberin, C. Cazorla, J. Hafid, et al.
Comparison between real-time PCR, conventional PCR and different staining techniques for diagnosing Pneumocystis jirovecii pneumonia from bronchoalveolar lavage specimens.
J Med Microbiol, 53 (2004), pp. 603-607
[36.]
D.R. Murdoch.
Molecular genetic methods in the diagnosis of lower respiratory tract F infections.
[37.]
G. Sanchez, X. Coronado, I. Zulantay, W. Apt, M. Gajardo, S. Solari, et al.
Monitoring the efficacy of specific treatment in chronic Chagas disease by polymerase chain reaction and flow cytometry analysis.
Parasite., 12 (2005), pp. 353-357
[38.]
S. Bretagne, J.M. Costa.
Towards a molecular diagnosis of invasive aspergillosis and disseminated candidosis.
FEMS Immunol Med Microbiol, 45 (2005), pp. 361-368
[39.]
I. Durand-Joly, M. Chabé, F. Soula, L. Delhaes, D. Camus, E. Dei-Cas.
Molecular diagnosis of Pneumocystis pneumonia.
FEMS Immunol Med Microbiol, 45 (2005), pp. 405-440
[40.]
R. Bialek, G.M. González, D. Begerow, U.E. Zelck.
Coccidioidomycosis and blastomycosis: Advances in molecular diagnosis.
FEMS Immunol Med Microbiol, 45 (2005), pp. 355-360
[41.]
T. Allice, M. Enrietto, F. Pittaluga, S. Barreto, A. Franchello, G. Marchiaro, et al.
Quantitation of cytomegalovirus DNA by real-time polymerase chain reaction in peripheral blood specimens of patients with solid organ transplants: Comparison with end-point PCR and pp65 antigen test.
J Med Virol, 78 (2006), pp. 915-922
[42.]
M.J. Rebollo, S.J. Garrido, D. Folgueira, E. Palenque, C. Diaz-Pedroche, C. Lumbreras, et al.
Blood and urine samples as useful sources for the direct detection of tuberculosis by polymerase chain reaction.
Diagn Microbiol Infect Dis, 56 (2006), pp. 141-146
[43.]
M.M. Muniz, C.V. Pizzini, J.M. Peralta, E. Reiss, R.M. Zancopé-Oliveira.
Genetic diversity of Histoplasma capsulatum strains isolated from soil, animals, and clinical specimens in Rio de Janeiro State, Brazil, by a PCR-based random amplified polymorphic DNA assay.
J Clin Microbiol, 39 (2001), pp. 4487-4494
[44.]
A.J. Guimaraes, J.D. Nosanchuk, M.R. Zancope-Oliveira.
Diagnosis of histoplasmosis.
Brazilian J Microbiol, 37 (2006), pp. 1-13
[45.]
L.J. Wheat.
Improvements in diagnosis of histoplasmosis.
Expert Opin Biol Ther, 6 (2006), pp. 1207-1221
[46.]
P. Couppie, C. Aznar, B. Carme, M. Nacher.
American histoplasmosis in developing countries with a special focus on patients with HIV: diagnosis, treatment, and prognosis.
Curr Opin Infect Dis, 19 (2006), pp. 443-449
[47.]
R.S. Axel, B. Hernández, M. Rodríguez, H. Romero.
Comparación del método de hemocultivo convencional con el de lisis/centrifugación modificado para el diagnóstico de fungemias.
Rev Iberoam Micol, 21 (2004), pp. 198-201
[48.]
J.A. Weydert, T.L. Van Natta, B.R. DeYoung.
Comparison of fungal culture versus surgical pathology examination in the detection of Histoplasma in surgically excised pulmonary granulomas.
Arch Pathol Lab Med, 131 (2007), pp. 780-783
[49.]
L.J. Wheat.
Antigen detection, serology, and molecular diagnosis of invasive mycoses in the immunocompromised host.
Transpl Infect Dis, 8 (2006), pp. 128-139
[50.]
A.J. Guimaraes, C.V. Pizzini, H.L. Matos-Guedes, P.C. Albuquerque, J.M. Peralta, A.J. Hamilton, et al.
ELISA for early diagnosis of histoplasmosis.
J Med Microbiol, 54 (2004), pp. 509-514
[51.]
M.M. Durkin, P.A. Connolly, L.J. Wheat.
Comparison of radioimmunoassay and enzyme-linked immunoassay methods for detection of Histoplasma capsulatum var. capsulatum antigen.
J Clin Microbiol, 35 (1997), pp. 2252-2255
[52.]
J.W. Pickering, H.W. Sant, C.A. Bowles, W.L. Roberts, G.L. Woods.
Evaluation of a (1→3)-β-D-Glucan assay for diagnosis of invasive fungal infections.
J Clin Microbiol, 43 (2005), pp. 5957-5962
[53.]
C.A. Hage, T.E. Davis, L. Egan, M. Parker, D. Fuller, A.M. LeMonte, et al.
Diagnosis of pulmonary histoplasmosis and blastomycosis by detection of antigen in bronchoalveolar lavage fluid using an improved second-generation enzyme-linked immunoassay.
Respir Med, 101 (2007), pp. 43-47
[54.]
M.D. Lindsley, H.L. Holland, S.L. Bragg, S.F. Hurst, K.A. Wannemuehler, C.J. Morrison.
Production and evaluation of reagents for detection of Histoplasma capsulatum antigenuria by enzyme immunoassay.
Clin Vaccine Immunol, 14 (2007), pp. 700-709
[55.]
B.L. Gómez, J.I. Figueroa, A.J. Hamilton, S. Diez, M. Rojas, A. Tobón, et al.
Detection of the 70-kilodalton Histoplasma capsulatum antigen in serum of histoplasmosis patients: correlation between antigenemia and therapy during follow-up.
J Clin Microbiol, 37 (1999), pp. 675-680
[56.]
L.J. Kricka.
Human anti-animal antibody interferences in immunological assays.
Clin Chem, 45 (1999), pp. 942-956
[57.]
B.L. Gómez, J.I. Figueroa, A.J. Hamilton, B.L. Ortiz, M.A. Robledo, A. Restrepo, et al.
Development of a novel antigen detection test for histoplasmosis.
J Clin Microbiol, 35 (1997), pp. 2618-2622
[58.]
L.J. Wheat, P. Connolly, M. Durkin, B.K. Book, M.D. Pescovitz.
Elimination of false-positive Histoplasma antigenemia caused by human antirabbit antibodies in the second-generation Histoplasma antigen assay.
Transpl Infect Dis, 8 (2006), pp. 219-221
[59.]
L.J. Wheat, E. Hackett, M. Durkin, P. Connolly, R. Petraitiene, WalshTJ, et al.
Histoplasmosis-associated cross-reactivity in the BioRad platelia Aspergillus enzyme immunoassay.
Clin vaccine immunol, 14 (2007), pp. 638-640
[60.]
S. Ranque, R. Pelletier, A. Michel-Nguyen, F. Dromer.
Platelia Aspergillus assay for diagnosis of disseminated histoplasmosis.
Eur J Clin Microbiol Infect Dis, 26 (2007), pp. 941-943
[61.]
J.L. Cloud, S.K. Bauman, B.P. Neary, K.G. Ludwig, E.R. Ashwood.
Performance characteristics of a polyclonal enzyme immunoassay for the quantitation of Histoplasma antigen in human urine samples.
Am J Clin Pathol, 128 (2007), pp. 18-22
[62.]
A. LeMonte, L. Egan, P. Connolly, M. Durkin, L.J. Wheat.
Evaluation of the IMMY ALPHA Histoplasma antigen enzyme immunoassay for diagnosis of histoplasmosis marked by antigenuria.
Clin Vaccine Immunol, 14 (2007), pp. 802-803
[63.]
L.J. Wheat.
Nonculture diagnostic methods for invasive fungal infections.
Curr Infect Dis Rep, 9 (2007), pp. 465-471
[64.]
C.M. Scheel, B. Samayoa, A. Herrera, M.D. Lindsley, L. Benjamin, Y. Reed, et al.
Development and evaluation of an enzyme-linked immunosorbent assay to detect Histoplasma capsulatum antigenuria in immunocompromised patients.
Clin Vacc Immunol., 16 (2009), pp. 852-858
[65.]
A. Eiler, S. Bertilsson.
Detection and quantification of Vibrio populations using denaturant gradient gel electrophoresis.
J Microbiol Methods, 67 (2006), pp. 339-348
[66.]
R. Bialek, J. Fischer, A. Feucht, L. Najvar, K. Dietz, J. Knobloch, et al.
Diagnosis and Monitoring of murine histoplasmosis by a Nested PCR assay.
J Clin Microbiol, 39 (2001), pp. 1506-1509
[67.]
R. Bialek, A. Feucht, C. Aepinus, G. Just-Nübling, V.J. Robertson, J. Knobloch, et al.
Evaluation of two nested PCR assays for detection of Histoplasma capsulatum DNA in Human tissue.
J Clin Microbiol, 40 (2002), pp. 1644-1647
[68.]
A. Porta, S. Colonna-Romano, I. Callebaut, A. Franco, L. Marzullo, G.S. Kobayashi, et al.
An homologue of the human 100-Kda protein (p100) is differentially expressed by Histoplasma capsulatum during Infection of murine macrophages.
Biochem Biophys Res Commun, 254 (1999), pp. 605-613
[69.]
V. Rickerts, R. Bialek, K. Tintelnot, V. Jacobi, G. Just-Nübling.
Rapid PCRBased Diagnosis of disseminated Histoplasmosis in an AIDS patient.
Eur J Clin Microbiol Infect Dis, 21 (2002), pp. 821-823
[70.]
C. Muñoz, B.L. Gómez, A. Tobón, K. Arango, A. Restrepo, M.M. Correa, et al.
Validation and clinical application of a molecular methods for identification of Histoplasma capsulatum in human specimens in Colombia, South America.
Clin Vacc Immunol, 17 (2010), pp. 62-67
[71.]
H.L. Matos-Guedes, A.J. Guimaraes, M.M. Muniz, C.V. Pizzini, A.J. Hamilton, J.M. Peralta, et al.
PCR assay for identification of Histoplasma capsulatum based on the nucleotide sequence of the M antigen.
J Clin Microbiol, 41 (2003), pp. 535-539
[72.]
A. Bracca, M.E. Tosello, J.E. Girardini, S.L. Amigot, C. Gomez, E. Serra.
Molecular detection of Histoplasma capsulatum var. capsulatum in human clinical samples.
J Clin Microbiol, 41 (2003), pp. 1753-1755
[73.]
W.H. Spencer, C.C. Chao, D.F. Shen, N.A. Rao.
Detection of Histoplasma capsulatum DNA in lesions of chronic ocular histoplasmosis syndrome.
Arch Ophthalmol, 121 (2003), pp. 1551-1555
[74.]
Y. Ueda, A. Sano, M. Tamura, T. Inomata, K. Kamei, K. Yakoyama, et al.
Diagnosis of histoplasmosis by detection of the internal transcribed spacer region of fungal rRNA gene from a paraffin-embedded skin sample from a dog in Japan.
Vet Micribiol, 94 (2003), pp. 219-224
[75.]
M.J. Buitrago, A. Gómez-López, A. Monzón, J.L. Rodríguez-Tudela, M. Cuenca-Estrella.
Evaluación de una técnica de PCR cuantitativa para el diagnóstico clínico de la histoplasmosis importada.
Enferm Infecc Microbiol Clin, 25 (2007), pp. 16-22
[76.]
Y.W. Tang, H. Li, M.M. Durkin, S.E. Sefers, S. Meng, P. Connolly, et al.
Urine polymerase chain reaction is not as urine antigen for the diagnosis of disseminated histoplasmosis.
Diagn Microbiol Infect Dis, 54 (2006), pp. 283-287
[77.]
J.I. Pounder, D. Hansen, G.L. Woods.
Identification of Histoplasma capsulatum, Blastomyces dermatitidis, and Coccidioides species by repetitive-sequence-based PCR.
J Clin Microbiol, 44 (2006), pp. 2977-2982
[78.]
M.J. Buitrago, J. Berenguer, MelladoE, J.L. Rodríguez-Tudela, M. Cuesta-Estrella.
Detection of imported histoplasmosis in serum of HIV-infected patients using a real-time PCR-based assay.
Eur J Clin Microbiol Infect Dis, 25 (2006), pp. 665-668
[79.]
D. Maubon, S. Simon, C. Aznar.
Histoplasmosis diagnosis using a polymerase chain reaction method.Application on human samples in French Guiana, South America.
Diagn Microbiol Infect Dis, 58 (2007), pp. 441-444
[80.]
S. Simon, V. Veron, R. Boukhari, D. Blanchet, C. Aznar.
Detection of Histoplasma capsulatum DNA in human samples by real-time polymerase chain reaction.
Diagn Microbiol Infect Dis, 66 (2010), pp. 268-273
[81.]
D.A. Carter, J.W. Taylor, B. Dechairo, A. Burt, G.L. Koenig, T.J. White.
Amplified single-nucleotide polymorphisms an (GA)n microsatellite marker reveal genetic differentiation between populations of Histoplasma capsulatum from the Americas.
Fungal Genet Biol, 34 (2001), pp. 37-48
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