Abstract
Histoplasmosis is a worldwide-distributed systemic mycosis caused by the dimorphic fungus Histoplasma capsulatum. Its clinical manifestations range from subclinical or mild respiratory illness to progressive disseminated histoplasmosis (PDH), a life-threatening disease, whose accurate diagnosis is still challenging and limited in many countries, where this disease is highly endemic. In this regard, Histoplasma antigen testing is now included in the WHO Essential Diagnostics List. The final diagnosis of histoplasmosis is established by culture and/or visualization of the yeast cells by cytology or histopathology using specific stains. However, both procedures have limited sensitivity to detect the disease and cultures are time-consuming. Antibody detection assays are effective for the subacute and chronic clinical forms of histoplasmosis. However, their sensitivity is low in the immunocompromised host. Several molecular “in-house” tests were also developed and showed promising results, but none of these tests are commercially available and their standardization and validation are still pending. Antigen detection assays have high sensitivity in PDH cases and are of great value for the follow-up of patients with histoplasmosis; however, cross-reactivity with other related fungi are common. In addition, this assay is expensive and only performed in few laboratories. Novel protein antigen candidates have been recently identified and produced by DNA-recombinant techniques in order to obtain standardized and specific reagents for the diagnosis of histoplasmosis, as opposed to the unspecific antigens or crude extracts currently used. This review describes the currently available assays, highlighting their strengths and limitations and reports the latest approaches to achieve reliable and rapid diagnostic tests for histoplasmosis.
Key points
• PDH causes thousands of deaths per year globally.
• Rapid accurate diagnosis of PDH is unfeasible in many regions.
• Fast, accurate, and low-cost diagnostic alternatives are currently under development.
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References
Adenis A, Nacher M, Hanf M, Basurko C, Dufour J, Huber F, Aznar C, Carme B, Couppie P (2014) Tuberculosis and histoplasmosis among human immunodeficiency virus-infected patients: a comparative study. Am J Trop Med Hyg 90(2):216–223. https://doi.org/10.4269/ajtmh.13-0084
Adenis A, Valdes A, Cropet C, McCotter OZ, Derado G, Couppie P, Chiller T, Nacher M (2018) Burden of HIV-associated histoplasmosis compared with tuberculosis in Latin America: a modelling study. Lancet Infect Dis 18(10):1150–1159. https://doi.org/10.1016/S1473-3099(18)30354-2
Almeida MA, Valdes A, Cropet C, McCotter OZ, Derado G, Couppie P, Chiller T, Nacher M (2016) Validation of Western blot for Histoplasma capsulatum antibody detection assay. BMC Infect Dis 16(1):1–8. https://doi.org/10.1186/s12879-016-1427-0
Almeida MA, Damasceno LS, Pizzini CV, Muniz M, Almeida-Paes R, Zancope-Oliveira RM (2019) Role of Western blot assay for the diagnosis of histoplasmosis in AIDS patients from a National Institute of Infectious Diseases in Rio de Janeiro, Brazil. Mycoses 62(3):261–267. https://doi.org/10.1111/myc.12877
Alvarado P, Pérez-Rojas Y, Zambrano EA, Gonzatti MI, Roschman-González A (2020) Improved serodiagnosis of histoplasmosis by use of deglycosylated extracellular released antigens of Histoplasma capsulatum. J Microbiol Methods 175:105981. https://doi.org/10.1016/j.mimet.2020.105981
Assi M, Iass EL, Wheat LJ (2011) Cross-Reactivity in the Histoplasma antigen enzyme immunoassay caused by sporotrichosis. Clin Vaccine Immunol 18(10):1781–1782. https://doi.org/10.1128/CVI.05017-11
Babady NE, Buckwalter SP, Hall L, Le Febre KM, Binnicker MJ, Wengenack NL (2011) Detection of Blastomyces dermatitidis and Histoplasma capsulatum from culture isolates and clinical specimens by use of real-time PCR. J Clin Microbiol 49(9):3204–3208. https://doi.org/10.1128/JCM.00673-11
Bahr NC, Antinori S, Wheat LJ, Sarosi GA (2015) Histoplasmosis infections worldwide: thinking outside of the Ohio River Valley. Curr Trop Med Rep 2(2):70–80. https://doi.org/10.1007/s40475-015-0044-0
Baker J, Setianingrum F, Wahyuningsih R, Denning DW (2019) Mapping histoplasmosis in South East Asia–implications for diagnosis in AIDS. Emerg Microbes Infect 8(1):1139–1145. https://doi.org/10.1080/22221751.2019.1644539
Becherer L, Borst N, Bakheit M, Frischmann S, Zengerle R, Von Stetten F (2020) Loop-Mediated Isothermal Amplification (LAMP)-review and classification of methods for sequence-specific detection. Anal Methods 12(6):717–746. https://doi.org/10.1039/c9ay02246e
Bialek R, Fischer J, Feucht A, Najvar LK, Dietz K, Knobloch J, Graybill JR (2001) Diagnosis and monitoring of murine histoplasmosis by a nested PCR assay. J Clin Microbiol 39(4):1506–1509. https://doi.org/10.1128/JCM.39.4.1506-1509.2001
Bialek R, Feucht A, Aepinus C, Robertson VJ, Hohle R (2002) Evaluation of two nested PCR assays for detection of Histoplasma capsulatum DNA in human tissue. J Clin Microbiol 40(5):1644–1647. https://doi.org/10.1128/JCM.40.5.1644
Bloch KC, Myint T, Raymond-Guillen L, Hage CA, Davis TE, Wright PW, Chow FC, Woc-Colburn L, Khairy RN, Street AC, Yamamoto T, Albers A, Wheat LJ (2018) Improvement in diagnosis of histoplasma meningitis by combined testing for Histoplasma antigen and immunoglobulin G and immunoglobulin M anti-Histoplasma antibody in cerebrospinal fluid. Clin Infect Dis 66(1):89–94. https://doi.org/10.1093/cid/cix706
Bracca A, Tosello ME, Girardini JE, Amigot SL, Gomez C, Serra E (2003) Molecular Detection of Histoplasma capsulatum var. capsulatum in Human Clinical Samples. J Clin Microbiol 41(4):1753–1755. https://doi.org/10.1128/JCM.41.4.1753-1755.2003
Brock EG, Reiss E, Pine L, Kaufman L (1984) Effect of periodate oxidation on the detection of antibodies against the M-antigen of histoplasmin by enzyme immunoassay (EIA) inhibition. Curr Microbiol 10(3):177–180. https://doi.org/10.1007/BF01576782
Buitrago MJ, Berenguer J, Mellado E, Rodríguez-Tudela JL, Cuenca-Estrella M (2006) Detection of Imported histoplasmosis in serum of HIV-infected patients using a real-time PCR-based assay. Eur J Clin Microbiol Infect Dis 25(10):665–668. https://doi.org/10.1007/s10096-006-0207-y
Buitrago MJ, Gómez-López A, Monzón A, Rodríguez-Tudela JL, Cuenca-Estrella M (2007) Evaluación de Una Técnica de PCR Cuantitativa Para El Diagnóstico Clínico de La Histoplasmosis Importada. Enferm Infecc Microbiol Clin 25(1):16–22. https://doi.org/10.1157/13096748
Buitrago MJ, Bernal-Martínez L, Castelli MV, Rodríguez-Tudela JL, Cuenca-Estrella M (2011) Histoplasmosis and Paracoccidioidomycosis in a non-endemic area: a review of cases and diagnosis. J Travel Med 18(1):26–33. https://doi.org/10.1111/j.1708-8305.2010.00477.x
Cáceres DH, Scheel CM, Tobón AM, Cleveland AA, Restrepo A, Brandt ME, Chiller T, Gómez BL (2014) Validation of an enzyme-linked immunosorbent assay that detects Histoplasma capsulatum antigenuria in Colombian patients with AIDS for diagnosis and follow-up during therapy. Clin Vaccine Immunol 21(9):1364–1368. https://doi.org/10.1128/CVI.00101-14
Cáceres DH, Zuluaga A, Arango-Bustamante K, De Bedout C, Tobón ÁM, Restrepo Á, Gomez BL, Cano LE, González Á (2015) Implementation of a training course increased the diagnosis of histoplasmosis in Colombia. Am J Trop Med Hyg 93(3):662–667. https://doi.org/10.4269/ajtmh.15-0108
Cáceres DH, Samayoa BE, Medina NG, Tobón AM, Guzmán BJ, Mercado D, Restrepo A, Chiller T, Arathoon EE, Gómez BL (2018) Multicenter validation of commercial antigenuria reagents to diagnose progressive disseminated histoplasmosis in people living with HIV/AIDS in two Latin American countries. J Clin Microbiol 56(6):1–10. https://doi.org/10.1128/JCM.01959-17
Cáceres DH, Antoine A, de Souza JVB, Gomez BL, Cruz KS, Pasqualotto AC, Ravasi G, Perez F, Chiller T, Guimarares de Lacerda MV, Nacher M (2019a) The Manaus declaration: current situation of histoplasmosis in the Americas, Report of the II Regional Meeting of the International Histoplasmosis Advocacy Group. Curr Fungal Infect Rep 13(4):244–249. https://doi.org/10.1007/s12281-019-00365-3
Cáceres DH, Knuth M, Derado G, Lindsley MD (2019b) Diagnosis of progressive disseminated histoplasmosis in advanced HIV: a meta-analysis of assay analytical performance. J Fungi 5(3):1–13. https://doi.org/10.3390/jof5030076
Cáceres DH, Gómez BL, Tobón AM, Chiller TM, Lindsley MD (2020) Evaluation of a Histoplasma antigen lateral flow assay for the rapid diagnosis of progressive disseminated histoplasmosis in Colombian patients with AIDS. Mycoses 63(2):139–144. https://doi.org/10.1111/myc.13023
Centers for Disease Control (1987) Revision of the CDC Surveillance Case Definition for Acquired Immunodeficiency Syndrome. Council of State and Territorial Epidemiologists; AIDS Program, Center for Infectious Diseases. MMWR Suppl 36(1):1S–15S
Cloud JL, Bauman SK, Neary BP, Ludwig KG, Ashwood ER (2007) Performance characteristics of a polyclonal enzyme immunoassay for the quantitation of Histoplasma antigen in human urine samples. Am J Clin Pathol 128(1):18–22. https://doi.org/10.1309/Q7879TYDW5D93QK7
Collela MT, Mata S, Hartung C, Pérez C, Roselló A, Olaizola C, Fernández C, Magaldi S, Toro F (2007) Detection of Histoplasma capsulatum by Nested-PCR in Clinical Specimens. Kasmera 35(2):156–163
Colonna-Romano S, Porta A, Franco A, Kobayashi GS, Maresca B (1998) Identification and Isolation by DDRT-PCR of Genes Differentially Expressed by Histoplasma capsulatum during Macrophages Infection. Microb Pathog 25(2):55–66. https://doi.org/10.1006/mpat.1998.0209
Confalonieri ML, Gandola L, Aiolfi S, Mazzoni A (1994) Histoplasmin sensitivity among a student population in Crema, Po Valley, Italy. New Microbiol 17(2):151–153
Connolly PA, Durkin MM, LeMonte AM, Hackett EJ, Wheat LJ (2007) Detection of Histoplasma antigen by a quantitative enzyme immunoassay. Clin Vaccine Immunol 14(12):1587–1591. https://doi.org/10.1128/CVI.00071-07
Cook AK, Cunningham LY, Cowell AK, Wheat LJ (2012) Clinical evaluation of urine Histoplasma capsulatum antigen measurement in cats with suspected disseminated histoplasmosis. J Feline Med Surg 14(8):512–515. https://doi.org/10.1177/1098612X12450121
Couppié P, Aznar C, Carme B, Nacher M (2006) American histoplasmosis in developing countries with a special focus on patients with HIV: diagnosis, treatment, and prognosis. Curr Opin Infect Dis 19(5):443–449. https://doi.org/10.1097/01.qco.0000244049.15888.b9
Crockett DK, Kushnir MM, Cloud JL, Ashwood ER, Rockwood AL (2012) Identification of Histoplasma-specific peptides in human urine. Int J Pept 2012(621329). https://doi.org/10.1155/2012/621329
Cunningham L, Cook A, Hanzlicek A, Harkin K, Wheat J, Goad C, Kirsch E (2015) Sensitivity and Specificity of Histoplasma Antigen Detection by Enzyme Immunoassay. J Am Anim Hosp Assoc 51(5):306–310. https://doi.org/10.5326/JAAHA-MS-6202
Da Silva Zatti M, Arantes TD, Lourenço Fernandes JA, Bay MB, Milan EP, Silva Naliato GF, Theodoro RC (2019) Loop-mediated isothermal amplification and nested PCR of the internal transcribed spacer (ITS) for Histoplasma capsulatum detection. PLoS Negl Trop Dis 13(8):1–20. https://doi.org/10.1371/journal.pntd.0007692
Dantas KC, De Freitas RS, da Silva MV, Criado PR, Luiz OC, Vicentini AP (2018) Comparison of Diagnostic Methods to Detect Histoplasma capsulatum in Serum and Blood Samples from AIDS Patients. PLoS One 13(1):1–12. https://doi.org/10.1371/journal.pone.0190408
de Freitas RS, Kamikawa CK, Pardini Vicentini A (2018) Fast protocol for the production of Histoplasma capsulatum antigens for antibody detection in the immunodiagnosis of histoplasmosis. Rev Iberoam Micol 35(1):27–31. https://doi.org/10.1016/j.riam.2017.04.004
de Matos Guedes HL, Guimarães AJ, Muniz Mde M, Pizzini CV, Hamilton AJ, Peralta JM, Deepe GS Jr, Zancopé-Oliveira RM (2003) PCR assay for identification of Histoplasma capsulatum based on the nucleotide sequence of the M antigen. J Clin Microbiol 41(2):535–539. https://doi.org/10.1128/jcm.41.2.535-539.2003
Deepe GS, Durose GG (1995) Immunobiological activity of recombinant H antigen from Histoplasma capsulatum. Infect Immun 63(8):3151–3157. https://doi.org/10.1128/IAI.63.8.3151-3157.1995
Denning DW (2016) Minimizing fungal disease deaths will allow the UNAIDS target of reducing annual AIDS deaths below 500 000 by 2020 to be realized. Philos Trans R Soc B BiolSci 371(1709). https://doi.org/10.1098/rstb.2015.0468
Donnelly JP, Chen SC, Kauffman CA, Steinbach WJ, Baddley JW, Verweij PE, Clancy CJ, Wingard JR, Lockhart SR, Groll AH, Sorrell TC, Bassetti M, Akan H, Alexander BD, Andes D, Azoulay E, Bialek R, Bradsher RW, Bretagne S, Calandra T, Caliendo AM, Castagnola E, Cruciani M, Cuenca-Estrella M, Decker CF, Desai SR, Fisher B, Harrison D, Heussel CP, Jensen HE, Kibbler CC, Kontoyiannis DP, Kullberg B, Lagrou K, Lamoth F, Lehrnbecher T, Loeffler J, Lortholary O, Maertens J, Marchetti O, Marr KA, Masur H, Meis JF, Morrisey CO, Nucci M, Ostrosky-Zeichner L, Pagano L, Patterson TF, Perfect JR, Racil Z, Roilides E, Ruhnke M, Schaefer Prokop S, Shoham S, Slavin MA, Stevens DA, Thompson GR, Vazquez JA, Viscoli C, Walsh J, Warris A, Wheat LJ, White PL, Zaoutis TE, Pappas PG (2020) Revision and Update of the Consensus Definitions of Invasive Fungal Disease From the European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium. Clin Infect Dis 71(6):1367–1376. https://doi.org/10.1093/cid/ciz1008
Durkin MM, Connolly PA, Wheat LJ (1997) Comparison of radioimmunoassay and enzyme-linked immunoassay methods for detection of Histoplasma capsulatum var. capsulatum antigen. J Clin Microbiol 35(9):2252–2255
Edwards PQ, Billings EL (1971) Worldwide Pattern of skin sensitivity to histoplasmin. Am J Trop Med Hyg 20(2):288–319
Elías NA, Cuestas ML, Sandoval M, Poblete G, Lopez-Daneri G, Jewtuchowicz V, Iovannitti C, Mujica MT (2012) Rapid identification of Histoplasma capsulatum directly from cultures by multiplex PCR. Mycopathol 174(5–6):451–456. https://doi.org/10.1007/s11046-012-9567-2
Falci DR, Hoffmann ER, Paskulin DD, Pasqualotto AC (2017) Progressive disseminated histoplasmosis: a systematic review on the performance of non-culture-based diagnostic tests. Braz J Infect Dis 21(1):7–11. https://doi.org/10.1016/j.bjid.2016.09.012
Falci DR, Monteiro AA, Braz Caurio CF, Magalhães TCO, Xavier MO, Basso RP, Melo M, Schwarzbold AV, Ferreira PRA, Vidal JE, Marochi JP, Godoy CSM, Soares RBA, Paste A, Bay MB, Pereira-Chiccola VL, Damasceno LS, Leitão TDMJS, Pasqualotto AC (2019) Histoplasmosis, an underdiagnosed disease affecting people living with HIV/AIDS in Brazil: results of a multicenter prospective cohort study using both classical mycology tests and Histoplasma urine antigen detection. Open Forum Infect Dis 6(4):ofz073. https://doi.org/10.1093/ofid/ofz073
Fielder SE, Meinkoth JH, Rizzi TE, Hanzlicek AS, Hallman RM (2019) Feline histoplasmosis presenting with bone and joint involvement: clinical and diagnostic findings in 25 cats. J Feline Med Surge 21(10):887–892. https://doi.org/10.1177/1098612X18806706
Frías De León MG, Arenas López G, Taylor ML, Acosta Altamirano G, Reyes-Montes Mdel R (2012) Development of specific sequence-characterized amplified region markers for detecting Histoplasma capsulatum in clinical and environmental samples. J Clin Microbiol 50(3):673–679. https://doi.org/10.1128/JCM.05271-11
Frías De León MG, Ramírez-Bárcenas JA, Rodríguez-Arellanes G, Velasco-Castrejón O, Taylor ML, Reyes-Montes MDR (2017) Usefulness of molecular markers in the diagnosis of occupational and recreational histoplasmosis outbreaks. Folia Microbiol (Praha) 62(2):111–116. https://doi.org/10.1007/s12223-016-0477-4
Frickmann H, Künne C, Hagen RM, Podbielski A, Normann J, Poppert S, Looso M, Kreikemeyer B (2019) Next-generation sequencing for hypothesis-free genomic detection of invasive tropical infections in poly-microbially contaminated, formalin-fixed, paraffin-embedded tissue samples-a proof-of-principle assessment. BMC Microbiol 19(1):1–19. https://doi.org/10.1186/s12866-019-1448-0
Furuie JL, Sun J, do Nascimento MMF, Gomes RR, Waculicz-Andrade CE, Sessegolo GC, Rodrigues AM, Galvão-Dias MA, de Camargo ZP, Queiroz-Telles F, Najafzadeh MJ, de Hoog SG, Vicente VA (2016) Molecular identification of Histoplasma capsulatum using rolling circle amplification. Mycoses 59(1):12–19. https://doi.org/10.1177/1098612X18806706
Gago S, Esteban C, Valero C, Zaragoza Ó, De La Bellacasa JP, Buitrago MJ (2014) A multiplex real-time PCR assay for identification of Pneumocystis jirovecii, Histoplasma capsulatum, and Cryptococcus neoformans/Cryptococcus gattii in samples from AIDS patients with opportunistic pneumonia. J Clin Microbiol 52(4):1168–1176
George RB, Lambert RS (1984) Significance of serum antibodies to Histoplasma capsulatum in Endemic areas. South Med J 77(2):161–163
Gomez BL, Figueroa JI, Hamilton AJ, Ortiz BL, Robledo MA, Restrepo A, Hay RJ (1997) Development of a novel antigen detection test for histoplasmosis. J Clin Microbiol 35(10):2618–2622
Gómez BL, Figueroa JI, Hamilton AJ, Ortiz BL, Robledo MA, Restrepo A, Hay RJ (1999) 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(3):675–680
Guimarães AJ, Pizzini CV, De Matos Guedes HL, Albuquerque PC, Peralta JM, Hamilton AJ, Zancopé-Oliveira RM (2004) ELISA for early diagnosis of histoplasmosis. J Med Microbiol 53(6):509–514. https://doi.org/10.1099/jmm.0.05469-0
Guimarães AJ, Nosanchuk JD, Zancopé-Oliveira RM (2006) Diagnosis of histoplasmosis. Braz J Microbiol 37(1):1–13. https://doi.org/10.1590/S1517-83822006000100001
Guimarães AJ, Pizzini CV, Almeida MA, Mauro J, Nosanchuk JD, Zancopé-oliveira RA (2010) Evaluation of an enzyme-linked immunosorbent assay using purified, deglycosylated histoplasmin for different clinical manifestations of histoplasmosis. Microbiol Res 1(1):7–14. https://doi.org/10.4081/mr.2010.e2
Gutierrez ME, Canton A, Connolly P, Zarnowski R, Wheat LJ (2008) Detection of Histoplasma capsulatum antigen in Panamanian Patients with disseminated histoplasmosis and AIDS. Clin Vaccine Immunol 15(4):681–683. https://doi.org/10.1128/CVI.00358-07
Hage CA, Davis TE, Egan L, Parker M, Fuller D, Lemonte AM, Durkin M, Connelly P, Wheat LJ, Blue-Hnidy D, Knox KS (2007) 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(1):43–47. https://doi.org/10.1016/j.rmed.2006.04.017
Hage CA, Davis TE, Fuller D, Egan L, Witt JR, Wheat LJ, Knox KS (2010) Diagnosis of histoplasmosis by antigen detection in BAL fluid. Chest 137(3):623–628. https://doi.org/10.1378/chest.09-1702
Hage CA, Ribes JA, Wengenack NL, Baddour LM, Assi M, McKinsey DS, Hammoud K, Alapat D, Babady EN, Parker M, Fuller DA, Noor A, Davis TE, Rodgers M, Connolly PA, El Haddad B, Wheat LJ (2011a) A multicenter evaluation of tests for diagnosis of histoplasmosis. Clin Infect Dis 53(5):448–454. https://doi.org/10.1093/cid/cir435
Hage CA, Kirsch EJ, Stump TE, Kauffman CA, Goldman M, Connolly P, Johnson PC, Wheat LJ, Baddley JW (2011b) Histoplasma antigen clearance during treatment of histoplasmosis in patients with AIDS determined by a quantitative antigen enzyme immunoassay. Clin Vaccine Immunol 18(4):661–666. https://doi.org/10.1128/CVI.00389-10
Hanzlicek AS, Meinkoth JH, Renschler JS, Goad C, Wheat LJ (2016) Antigen concentrations as an indicator of clinical remission and disease relapse in cats with histoplasmosis. J Vet Intern Med 30(4):1065–1073. https://doi.org/10.1111/jvim.13962
Hoffmann ER, Daboit TC, Paskulin DD, Monteiro AA, Falci DR, Linhares T, Flores JM, Goldani LZ, de Melo MG, Behar PR, Pasqualotto AC (2017) Disseminated histoplasmosis and AIDS: a prospective and multicentre study to evaluate the performance of different diagnostic tests. Mycoses 60(1):20–24. https://doi.org/10.1111/myc.12536
Holbrook ED, Edwards JA, Youseff BH, Rappleye CA (2011) Definition of the extracellular proteome of pathogenic-phase Histoplasma capsulatum. J Proteome Res 10(4):1929–1943. https://doi.org/10.1021/pr1011697
Holbrook ED, Kemski MM, Richer SM, Wheat LJ, Rappleye CA (2014) Glycosylation and immunoreactivity of the Histoplasma capsulatum Cfp4 yeast-phase exoantigen. Infect Immun 82(10):4414–4425. https://doi.org/10.1128/IAI.01893-14
Homei A, Worboys M (2013) Chapter 4, Endemic Mycoses and Allergies: Diseases of Social Change. In: Fungal disease in Britain and the United States 1850–2000: Mycoses and Modernity. Basingstoke (UK): Palgrave Macmillan. Available from: https://www.ncbi.nlm.nih.gov/books/NBK169221/
Incorporated G-P (2011) AccuProbe Histoplasma capsulatum culture identification test. Growth (Lakeland)
Kasuga T, White TJ, Koenig G, Mcewen J, Restrepo A, Castañeda E, Da Silva Lacaz CDA, Heins-Vaccari EM, De Freitas RS, Zancopé-Oliveira RM, Qin Z, Negroni R, Carter DA, Mikami Y, Tamura M, Taylor ML, Miller GF, Poonwan N, Taylor JW (2003) Phylogeography of the fungal pathogen Histoplasma capsulatum. Mol Ecol 12(12):3383–3401. https://doi.org/10.1046/j.1365-294X.2003.01995.x
Kauffman CA (2008) Diagnosis of histoplasmosis in immunosuppressed patients. Curr Opin Infect Dis 21(4):421–425. https://doi.org/10.1097/QCO.0b013e328306eb8d
Kaufman L (1971) Serological Tests for histoplasmosis: their use and interpretation. In: Thomas CC (ed) Histoplasmosis: Proceedings of the Second National Conference Held at the Center for Disease Control. Springfield, Illinois, Atlanta, pp 321–326
Kaufman L, Kovacs JA, Reiss E (1997) Clinical immunomycology. In: de Macario EC, Folds JD, Lane HC, Nakamura RM (eds) Manual of Clinical Laboratory Immunology, 5th edn. American Society for Microbiology, Washington D.C, pp 575–584
Klugman HB, Lurie HI (1963) Systemic histoplasmosis in South Africa. A review of the previous cases and a report of an additional case--the first successfully treated. S Afr Med J 37:29–31
Koepsell SA, Hinrichs SH, Iwen PC (2012) Applying a real-time PCR assay for Histoplasma capsulatum to clinically relevant formalin-fixed paraffin-embedded human tissue. J Clin Microbiol 50(10):3395–3397. https://doi.org/10.1128/JCM.01705-12
Lau AF, Drake SK, Calhoun LB, Henderson CM, Zelazny AM (2013) Development of a clinically comprehensive database and a simple procedure for identification of molds from solid media by matrix-assisted laser desorption ionization-time of flight mass spectrometry. J Clin Microbiol 51(3):828–834. https://doi.org/10.1128/JCM.02852-12
LeMonte A, Egan L, Connolly P, Durkin M, Wheat LJ (2007) Evaluation of the IMMY ALPHA Histoplasma antigen enzyme immunoassay for diagnosis of histoplasmosis marked by antigenuria. Clin Vaccine Immunol 14(6):802–803. https://doi.org/10.1128/CVI.00035-07
Lindsley MD (2013) The future of fungal serology. Curr Fungal Infect Rep 7(3):161–170. https://doi.org/10.1007/s12281-013-0146-x
Lindsley MD, Hurst SF, Iqbal NJ, Morrison CJ (2001) Rapid identification of dimorphic and yeast-like fungal pathogens using specific DNA probes. J Clin Microbiol 39(10):3505–3511. https://doi.org/10.1128/JCM.39.10.3505-3511.2001
Lindsley MD, Holland HL, Bragg SL, Hurst SF, Wannemuehler KA, Morrison CJ (2007) Production and evaluation of reagents for detection of Histoplasma capsulatum antigenuria by enzyme immunoassay. Clin Vaccine Immunol 14(6):700–709. https://doi.org/10.1128/CVI.00083-07
López LF, Muñoz CO, Cáceres DH, Tobón ÁM, Loparev V, Clay O, Chiller T, Litvintseva A, Gade L, González Á, Gómez BL (2017) Standardization and validation of real time PCR assays for the diagnosis of histoplasmosis using three molecular targets in an animal model. PLoS One 12(12):1–15. https://doi.org/10.1371/journal.pone.0190311
Martagon-Villamil J, Shrestha N, Sholtis M, Isada CM, Hall GS, Bryne T, Lodge BA, Barth Reller L, Procop GW (2003) Identification of Histoplasma capsulatum from culture extracts by real-time PCR. J Clin Microbiol 41(3):1295–1298. https://doi.org/10.1128/JCM.41.3.1295-1298.2003
Maubon D, Simon S, Aznar C (2007) Histoplasmosis diagnosis using a polymerase chain reaction method. Application on human samples in French Guiana, South America. Diagn Microbiol Infect Dis 58(4):441–444. https://doi.org/10.1016/j.diagmicrobio.2007.03.008
McGill JE, Hanzlicek AS, Kukanich KS, Norsworthy GD, Cook AK (2018) Pretreatment Histoplasma capsulatum urine enzymatic immunoassay concentrations do not correlate with outcome but may be influenced by renal function in cats with histoplasmosis. J Feline Med Surg 20(12):1177–1179. https://doi.org/10.1177/1098612X18761440
McLeod DSA, Mortimer RH, Perry-Keene DA, Allworth A, Woods ML, Perry-Keene J, McBride WJH, Coulter C, Robson JMB (2011) Histoplasmosis in Australia: report of 16 cases and literature review. Med 90(1):61–68. https://doi.org/10.1097/MD.0b013e318206e499
McTaggart LR, Copeland JK, Surendra A, Wang PW, Husain S, Coburn B, Guttman DS, Kus JV (2019) Mycobiome sequencing and analysis applied to fungal community profiling of the lower respiratory tract during fungal pathogenesis. Front Microbiol 10:1–12. https://doi.org/10.3389/fmicb.2019.00512
Moreira da Silva R, da Silva Neto JR, Santos CS, Cruz KS, Frickmann H, Poppert S, Koshikene D, De Souza JVB (2015) Fluorescent in situ hybridization of pre-incubated blood culture material for the rapid diagnosis of histoplasmosis. Med Mycol 53(2):160–164. https://doi.org/10.1093/mmy/myu080
Muñoz CO, Gómez BL, Tobón A, Arango K, Restrepo A, Correa MM, Muskus C, Cano LE, González A (2010) Validation and clinical application of a molecular method for identification of Histoplasma capsulatum in human specimens in Colombia, South America. Clin Vaccine Immunol 17(1):62–67. https://doi.org/10.1128/CVI.00332-09
Muraosa Y, Toyotome T, Yahiro M, Watanabe A, Shikanai-Yasuda MA, Kamei K (2016) Detection of Histoplasma capsulatum from clinical specimens by cycling probe-based real-time PCR and nested real-time PCR. Med Mycol 54(4):433–438. https://doi.org/10.1093/mmy/myv106
Murray PR (1991) Comparison of the lysis-centrifugation and agitated biphasic blood culture systems for detection of fungemia. J Clin Microbiol 29(1):96–98
Nacher M, Adenis A, Mc Donald S, Do Socorro Mendonca Gomes M, Singh S, Lopes Lima I, Malcher Leite R, Hermelijn S, Wongsokarijo M, Van Eer M, Marques Da Silva S, Mesquita Da Costa M, Silva M, Calvacante M, do Menino Jesus Silva Leitao T, Gómez BL, Restrepo A, Tobon A, Canteros CE, Aznar C, Blanchet D, Vantilcke V, Vautrin C, Boukhari R, Chiller T, Scheel C, Ahlquist A, Roy M, Lortholary O, Carme B, Couppié P, Vreden S (2013) Disseminated histoplasmosis in HIV-infected patients in South America: a neglected killer continues on its rampage. PLoS Negl Trop Dis 7(11):7–9. https://doi.org/10.1371/journal.pntd.0002319
Nacher M, Blanchet D, Bongomin F, Chakrabarti A, Couppié P, Demar M, Denning DW, Djossou F, Epelboin L, Govender N, Leitão T, Mac Donald S, Mandengue C, Marques da Silva SH, Oladele R, Panizo MM, Pasqualotto A, Ramos R, Swaminathan S, Rodriguez-Tudela JL, Vreden S, Zancopé-Oliveira R, Adenis A (2018) Histoplasma capsulatum antigen detection tests as an essential diagnostic tool for patients with advanced HIV disease in low and middle income countries: a systematic review of diagnostic accuracy studies. PLoS Negl Trop Dis 12(10):1–12. https://doi.org/10.1371/journal.pntd.0006802
Ohno H, Tanabe K, Umeyama T, Kaneko Y, Yamagoe S, Miyazaki Y (2013) Application of nested PCR for diagnosis of histoplasmosis. J Infect Chemother 19(5):999–1003
Oladele RO, Ayanlowo OO, Richardson MD, Denning DW (2018) Histoplasmosis in Africa: an emerging or a neglected disease? PLoS Negl Trop Dis 12(1). https://doi.org/10.1371/journal.pntd.0006046
Pan B, Chen M, Pan W, Liao W (2013) Histoplasmosis: a new endemic fungal infection in China? Review and Analysis of Cases. Mycoses 56(3):212–221. https://doi.org/10.1111/myc.12029
Persaud SP, Lawton T, Burnham CD, Anderson NW (2019) Comparison of urine antigen assays for the diagnosis of Histoplasma capsulatum infection. J Appl Lab Med 4(3):370–382. https://doi.org/10.1373/jalm.2018.028910
Picardi JL, Kauffman CA, Schwarz J, Phair JP (1976) Detection of precipitating antibodies to Histoplasma capsulatum by counterimmunoelectrophoresis. Am Rev Respir Dis 114(1):171–176. https://doi.org/10.1164/arrd.1976.114.1.171
Pine L, Boone CJ, McLaughlin D (1966) Antigenic properties of the cell wall and other fractions of the yeast form of Histoplasma capsulatum. J Bacteriol 91(6):2158–2168. https://doi.org/10.1128/JB.91.6.2158-2168.1966
Pizzini CV, Zancopé-Oliveira RM, Reiss E, Hajjeh R, Kaufman L, Peralta JM (1999) Evaluation of a Western blot test in an outbreak of acute pulmonary histoplasmosis. Clin Diagn Lab Immunol 6(1):20–23. https://doi.org/10.1128/cdli.6.1.20-23.1999
Porta A, Colonna-Romano S, Callebaut I, Franco A, Marzullo L, Kobayashi GS, Maresca B (1999) 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(3):605–613. https://doi.org/10.1006/bbrc.1998.9894
Raman C, Khardori N, Tewari RP, Von Behren LA, Wheat LJ (1990) Evaluation of an ELISA for the detection of anti-Histoplasma ribosomal and antihistoplasmin antibodies in histoplasmosis. J Clin Lab Anal 4(3):199–207. https://doi.org/10.1002/jcla.1860040311
Randhawa HS, Gugnani HC (2018) Occurrence of histoplasmosis in the Indian sub-continent: An Overview and Update. J Med Res Pract 7(3):71–83. https://doi.org/10.20936/jmrp/07/03/02
Reid TM, Schafer MP (1999) Direct detection of Histoplasma capsulatum in soil suspensions by two-stage PCR. Mol Cell Probes 13(4):269–273. https://doi.org/10.1006/mcpr.1999.0247
Richer SM, Smedema ML, Durkin MM, Herman KM, Hage CA, Fuller D, Wheat LJ (2016) Improved diagnosis of acute pulmonary histoplasmosis by combining antigen and antibody detection. Clin Infect Dis 62(7):896–902. https://doi.org/10.1093/cid/ciw007
Rothenburg L, Hanzlicek AS, Payton ME (2019) A monoclonal antibody-based urine Histoplasma antigen enzyme immunoassay (IMMY®) for the diagnosis of histoplasmosis in cats. J Vet Intern Med 33(2):603–610. https://doi.org/10.1111/jvim.15379
Santiago AR, Hernández B, Rodríguez M, Romero H (2004) A comparative study of blood voncentional method vs. a modified lysis/centrifugation technique for the diagnosis of fungemias. Rev Iberoam Micol 21(4):198–201
Scheel CM, Samayoa B, Herrera A, Lindsley MD, Benjamin L, Reed Y, Hart J, Lima S, Rivera BE, Raxcaco G, Chiller T, Arathoon E, Gómez BL (2009) Development and evaluation of an enzyme-linked immunosorbent assay to detect Histoplasma capsulatum antigenuria in immunocompromised patients. Clin Vaccine Immunol 16(6):852–858. https://doi.org/10.1128/CVI.00066-09
Scheel CM, Zhou Y, Theodoro RC, Abrams B, Balajee SA, Litvintseva AP (2014) Development of a loop-mediated isothermal amplification method for detection of Histoplasma capsulatum DNA in clinical samples. J Clin Microbiol 52(2):483–488. https://doi.org/10.1128/JCM.02739-13
Schestatsky P, Chedid MF, Amaral OB, Unis G, Oliveira FM, Severo LC (2006) Isolated central nervous system histoplasmosis in immunocompetent hosts: a series of 11 cases. Scand J Infect Dis 38(1):43–48. https://doi.org/10.1080/00365540500372895
Sharma A, Johri BN, Shriniwas (1982) An enzyme immunoassay for yeast and mycelial phase-specific antibodies in histoplasmosis. J Immunol Methods 50:115–121
Simon S, Veron V, Boukhari R, Blanchet D, Aznar C (2010) Detection of Histoplasma capsulatum DNA in human samples by real-time polymerase chain reaction. Diagn Microbiol Infect Dis 66(3):268–273 https://doi.org/10.1016/j.diagmicrobio.2009.10.010
Sotgiu G, Mantovani A, Mazzoni A (1970) Histoplasmosis in Europe. Mycopathol Mycol Appl 41(1–2):53–74
Swartzentruber S, Rhodes L, Kurkjian K, Zahn M, Brandt ME, Connolly P, Wheat LJ (2009a) Diagnosis of acute pulmonary histoplasmosis by antigen detection. Clin Infect Dis 49(12):1878–1882. https://doi.org/10.1086/648421
Swartzentruber S, LeMonte A, Witt J, Fuller D, Davis T, Hage C, Connolly P, Durkin M, Wheat LJ (2009b) Improved detection of Histoplasma antigenemia following dissociation of immune complexes. Clin Vaccine Immunol 16(3):320–322. https://doi.org/10.1128/CVI.00409-08
Tang YW, Li H, Durkin MM, Sefers SE, Meng S, Connolly PA, Stratton CW, Wheat LJ (2006) Urine Polymerase chain reaction is not as sensitive as urine antigen for the diagnosis of disseminated histoplasmosis. Diagn Microbiol Infect Dis 54(4):283–287. https://doi.org/10.1016/j.diagmicrobio.2005.10.008
Theel ES, Jespersen DJ, Harring J, Mandrekar J, Binnicker MJ (2013) Evaluation of an enzyme immunoassay for detection of Histoplasma capsulatum antigen from urine specimens. J Clin Microbiol 51(11):3555–3559. https://doi.org/10.1128/JCM.01868-13
Theel ES, Harring JA, Dababneh AS, Rollins LO, Bestrom JE, Jespersen DJ (2015) Reevaluation of commercial reagents for detection of Histoplasma capsulatum antigen in urine. J Clin Microbiol 53(4):1198–1203. https://doi.org/10.1128/JCM.03175-14
Toranzo AI, Tiraboschi IN, Fernández N, Ibarra-Camou B, Rivas MC, Lee W, Davel G, Canteros CE (2009) Diagnóstico Molecular de Histoplasmosis Humana En Muestras de Sangre Entera. Rev Argent Microbiol 41(1):20–26
Torres M, Díaz H, Herrera T, Sada E (1993) Evaluation of enzyme linked immunosorbent-assay and Western blot for diagnosis of histoplasmosis. Rev Inv Clín 45(2):155–160
Torres-González P, Niembro-Ortega MD, Martínez-Gamboa A, Ahumada-Topete VH, Andrade-Villanueva J, Araujo-Meléndez J, Chaparro-Sánchez A, Crabtree-Ramírez B, Cruz-Martínez S, Gamboa-Domínguez A, Flores-Barrientos OI, Gaytán-Martínez JE, González-Hernández LA, Hernández-León C, Lozano-Fernandez VH, Manríquez-Reyes M, Magaña-Aquino M, Martínez-Ayala P, Ramírez-Hinojosa JP, Rangel-Cordero A, Rivera-Martínez NE, Reyes-Gutiérrez E, Reyes-Terán G, Rodríguez-Zulueta P, Ruíz-Quiñones J, Santiago-Cruz J, Velázquez-Zavala NG, Sifuentes-Osornio J, Ponce de León A (2018) Diagnostic accuracy cohort study and clinical value of the Histoplasma urine antigen (ALPHA Histoplasma EIA) for disseminated histoplasmosis among HIV Infected patients: a multicenter study. PLoS Negl Trop Dis 12(11):1–16. https://doi.org/10.1371/journal.pntd.0006872
Toscanini MA, González Maglio D, Capece P, Posse G, Iovannitti CA, Nusblat AD, Cuestas ML (2020) Histoplasma capsulatum 100-kilodalton antigen: recombinant production, characterization, and evaluation of its possible application in the diagnosis of histoplasmosis. Appl Microbiol Biotechnol 104(13):5861–5872. https://doi.org/10.1007/s00253-020-10570-7
Toyotome T, Watanabe A, Ochiai E, Kamei K (2015) N-acetylated α-linked acidic dipeptidase is identified as an antigen of Histoplasma capsulatum. Biochem Biophys Res Commun 458(3):483–487. https://doi.org/10.1016/j.bbrc.2015.01.129
Valero C, Buitrago MJ, Gago S, Quiles-Melero I, Garćia-Rodríguez J (2018) A matrix-assisted laser desorption/ionization time of flight mass spectrometry reference database for the identification of Histoplasma capsulatum. Med Mycol 56(3):307–314. https://doi.org/10.1093/mmy/myx047
Wheat LJ (1992) Histoplasmosis in Indianapolis. Clin Infect Dis 14(Suppl 1):S91–S99. https://doi.org/10.1093/clinids/14-Supplement_1-S91
Wheat LJ (1995) Endemic mycoses in AIDS: a clinical review. Clin Microbiol Rev 8(1):146–159. https://doi.org/10.1128/cmr.8.1.146-159.1995
Wheat LJ (2006) Improvements in diagnosis of histoplasmosis. Expert Opin Biolog Ther 6(11):1207–1221. https://doi.org/10.1517/14712598.6.11.1207
Wheat LJ, Kauffman CA (2003) Histoplasmosis. Infect Dis Clin N Am 17(1):1–19. https://doi.org/10.1016/s0891-5520(02)00039-9
Wheat LJ, Slama TG, Norton JA, Kohler RB, Eitzen HE, French ML, Sathapatayavongs B (1982a) Risk factors for disseminated or fatal histoplasmosis. Analysis of a large urban outbreak. Ann Intern Med 96(2):159–163
Wheat LJ, French MLV, Kohler RB, Zimmerman SE, Smith WR, Norton JA, Eitzen HE, Smith CD, Slama TG (1982b) The diagnostic laboratory tests for histoplasmosis. Analysis of experience in a large urban outbreak. Ann Intern Med 97(5):680–685. https://doi.org/10.1016/S0002-9343(89)80820-4
Wheat LJ, Kohler TB, Tewari RP (1986) Diagnosis of disseminated histoplasmosis by detection of Histoplasma capsulatum antigen in serum and urine specimens. New Eng J Med 314(2):83–88. https://doi.org/10.1056/NEJM198601093140205
Wheat LJ, Connolly-Stringfield P, Kohler RB, Frame PT, Gupta MR (1989a) Histoplasma capsulatum polysaccharide antigen detection in diagnosis and management of disseminated histoplasmosis in patients with acquired immunodeficiency syndrome. Am J Med 87(4):396–400
Wheat LJ, Kohler RB, Tewari RP, Garten M, French MLV (1989b) Significance of Histoplasma antigen in the cerebrospinal fluid of patients with meningitis. Arch Intern Med 149(2):302–304
Wheat LJ, Connolly P, Blair R, Connolly K, Garringer T, Katz BP (1991) Histoplasmosis relapse in patients with AIDS: detection using Histoplasma capsulatum variety capsulatum antigen levels. Ann Intern Med 115(12):936–941
Wheat LJ, Connolly-Stringfield P, Williams B, Connolly K, Blair R, Bartlett M, Durkin M (1992) Diagnosis of histoplasmosis in patients with the acquired immunodeficiency syndrome by detection of Histoplasma capsulatum polysaccharide antigen in bronchoalveolar lavage fluid. Am Rev Respir Dis 145(6):1421–1424
Wheat LJ, Wheat H, Connolly P, Kleiman M, Supparatpinyo K, Nelson K, Bradsher R, Restrepo A (1997) Cross-reactivity in Histoplasma capsulatum variety capsulatum antigen assays of urine samples from patients with endemic mycoses. Clin Infect Dis 24(6):1169–1171. https://doi.org/10.1086/513647
Wheat LJ, Connolly P, Durkin M, Book BK, Tector AJ, Fridell J, Pescovitz MD (2004) False-positive Histoplasma antigenemia caused by antithymocyte globulin antibodies. Transpl Infect Dis 6(1):23–27. https://doi.org/10.1111/j.1399-3062.2004.00045.x
Wheat LJ, Connolly PA, Durkin M, Book BK, Pescovitz MD (2006) Elimination of false-positive Histoplasma antigenemia caused by human anti-rabbit antibodies in the second-generation Histoplasma antigen assay. Transpl Infect Dis 8(1):219–221
Wheat LJ, Freifeld AG, Kleiman MB, Baddley JW, McKinsey DS, Loyd JE, Kauffman CA (2007a) Clinical practice guidelines for the management of patients with histoplasmosis: 2007 update by the Infectious Diseases Society of America. Clin Infect Dis 45(7):807–825. https://doi.org/10.1086/521259
Wheat LJ, Witt J, Durkin JWM, Connolly P (2007b) Reduction in false antigenemia in the second generation histoplasma antigen assay. Med Mycol 45(2):169–171. https://doi.org/10.1080/13693780601185947
Wheat LJ, Azar MM, Bahr NC, Spec A, Relich RF, Hage C (2016) Histoplasmosis. Infect Dis Clin N Am 30(1):207–227. https://doi.org/10.1016/j.idc.2015.10.009
Wheat LJ, Myint T, Guo Y, Kemmer P, Hage C, Terry C, Azar MM, Riddell J, Ender P, Chen S, Shehab K, Cleveland K, Esguerra E, Johnson J, Wright P, Douglas V, Vergidis P, Ooi W, Baddley J, Bamberger D, Khairy R, Vikram H, Jenny-Avital E, Sivasubramanian G, Bowlware K, Pahud B, Sarria J, Tsai T, Assi M, Mocherla S, Prakash V, Allen D, Passaretti C, Huprikar S, Anderson A (2018) Central nervous system histoplasmosis. Med 97(13):1–8. https://doi.org/10.1097/MD.0000000000010245
WHO (2019) Second WHO Model List of Essential In Vitro Diagnostics. https://www.who.int/medical_devices/publications/Standalone_document_v8.pdf?ua=1 (July 2, 2020)
Zancopé-Oliveira RM, Bragg SL, Reiss E, Wanke B, Peralta JM (1994) Effects of Histoplasmin M Antigen chemical and enzymatic deglycosylation on cross-reactivity in the enzyme-linked immunoelectrotransfer blot method. Clin Diagn Lab Immunol 1(4):390–393. https://doi.org/10.1128/cdli.1.4.390-393.1994
Zancopé-Oliveira RM, Reiss E, Lott TJ, Mayer LW, Deepe GS (1999) Molecular Cloning, Characterization, and Expression of the M Antigen of Histoplasma capsulatum. Infect Immun 67(4):1947–1953. https://doi.org/10.1128/.67.4.1947-1953.1999
Zhang X, Gibson B, Daly TM (2013) Evaluation of commercially available reagents for diagnosis of histoplasmosis infection in immunocompromised patients. J Clin Microbiol 51(12):4095–4101. https://doi.org/10.1128/JCM.02298-13
Zhang C, Lei GS, Lee CH, Hage CA (2015) Evaluation of two new enzyme immunoassay reagents for diagnosis of histoplasmosis in a cohort of clinically characterized patients. Med Mycol 53(8):868–873. https://doi.org/10.1093/mmy/myv062
Zhang HC, Zhang QR, Ai JW, Cui P, Wu HL, Zhang WH, Wang T (2020) The role of bone marrow metagenomics next-generation sequencing to differential diagnosis among visceral leishmaniasis, histoplasmosis, and Talaromycosis marneffei. Int J Lab Hematol 42(2):e52–e54. https://doi.org/10.1111/ijlh.13103
Zimmerman SE, Connolly Stringfield P, Wheat LJ, French MLV, Kohler RB (1989) Comparison of sandwich solid-phase radioimmunoassay and two enzyme-linked immunosorbent assays for detection of Histoplasma capsulatum polysaccharide antigen. J Infect Dis 160(4):678–685. https://doi.org/10.1093/infdis/160.4.678
Zimmerman SE, French MLV, Kleiman MB, Wheat LJ (1990) Evaluation of an enzyme-linked immunosorbent assay that uses ferrous metal beads for determination of antihistoplasmal immunoglobulins G and M. J Clin Microbiol 28(1):59–64. https://doi.org/10.1128/jcm.28.1.59-64.1990
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ADN and MLC are members of the Argentinean Research Council (CONICET). MAT thanks CONICET for the PhD scholarship.
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This work was supported by grants from Agencia Nacional de Promoción Científica y Técnica (ANPCyT, Grant PICT 2018-02186) and from Universidad de Buenos Aires (Grant UBACyT 20020190100261BA).
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Toscanini, M.A., Nusblat, A.D. & Cuestas, M.L. Diagnosis of histoplasmosis: current status and perspectives. Appl Microbiol Biotechnol 105, 1837–1859 (2021). https://doi.org/10.1007/s00253-021-11170-9
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DOI: https://doi.org/10.1007/s00253-021-11170-9