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HISTOPLASMOSIS: DIAGNOSTIC CHALLENGES Editorial case reports 2019; 5(2) https://doi.org/10.15446/cr.v5n2.80200 HISTOPLASMOSIS: DIAGNOSTIC CHALLENGES Editorial María Guadalupe Frías-De León Hospital Regional de Alta Especialidad de Ixtapaluca - Research Unit - Ixtapaluca - Mexico. Universidad Nacional Autónoma de México - Faculty of Medicine - Department of Microbiology and Parasitology - Mexico DF - Mexico. Corresponding author María Guadalupe Frías-De León. Department of Microbiology and Parasitology, Faculty of Medicine, Universidad Nacional Autónoma de México. Mexico D.F. Mexico. Email: [email protected] Received: 25/05/2019 Accepted: 21/06/2019 case reports Vol. 5 No. 2: 85-8 86 Histoplasmosis is an infection usually Histoplasmosis mostly affects the lungs; caused by a fungal pathogen that, in most cases, however, the clinical presentation depends on occurs in the respiratory tract, which explains two variables: the load of infectious particles the high frequency of clinical manifestations in in the inoculum and the immune status of the the lungs. (1) This mycosis is endemic in the patient. It has been reported that in 5-10% of Americas (Mississippi and Ohio River Valley, cases, the infection spreads systemically to other USA; Central and South America; and the organs to be controlled by an immune system West Indies), while reports in areas of Asia, without alteration. Progressive disseminated Africa, Australia, and Oceania are mainly asso- disease occurs more often in patients with ciated with the pandemic of acquired immune human immunodeficiency virus (HIV) infection deficiency syndrome (AIDS). In Europe, cases and lower CD4 T-cell counts (<200 cells/ are on the rise because of the speculation of mm3), or in therapy with tumor necrosis factor a global distribution of histoplasmosis, and inhibiting agents, in which mortality rates are emphasis has been on improving methods high if diagnosis and treatment are not timely. for its diagnosis. (2,3) The symptoms of progressive histoplasmo- The etiological agent of histoplasmosis is sis are nonspecific, so its differentiation with the dimorphic fungus Histoplasma capsula- other infections, especially tuberculosis, is a tum, which is widely distributed in soils with challenge, even to determine the presence of high nitrogen content (contaminated with coinfections that occur frequently in patients droppings from bats or birds) both in endemic with HIV/AIDS. (1,2,4) areas and outside them. (2) From a taxonomic The laboratory tests available for the standpoint and based on molecular tests, conventional diagnosis of this fungal infection Sepúlveda et al. (1) proposed a new classi- have several limitations: fication of the species of Histoplasma. They were previously classified into three varieties: 1) Collecting blood, respiratory tract or tissue H. capsulatum var. capsulatum, pathogen samples for cultures is the golden stan- for humans in America; H. capsulatum var. dard, but sensitivity is variable based on duboisii, pathogen for humans in Africa; and the immunity of the patient, so the culture H. capsulatum var. farciminosum, pathogen sometimes yields false-negative results. In for equines. Currently, the following classifi- addition, Histoplasma isolation may require cation is used: H. capsulatum sensu stricto, up to six weeks for optimal growth. in Panama; H. mississippiense sp. nov. and 2) Immunological tests can detect antigens H. ohiense sp. nov. in North America; and H. or antibodies in serum and other biological suramericanum sp. nov. in South America. fluids, but the detection of antibodies can The description of these species has clinical give false-negative results due to its low and epidemiological implications, as there sensitivity in immunosuppressed patients are differences between them in terms of (particularly patients with AIDS, in whom the virulence and resistance to antifungal agents, production of antibodies decreases); how- as is the case of H. mississippiense, which is ever, antigen detection in these individuals less virulent but has greater resistance to the is more sensitive. Antigenic cross-reactivity most used antifungal antibiotics. (1) with other fungi may also occur, causing histoplasmosis: diagnostic challenges false-positive results in patients with other serological and even molecular test results 87 mycoses such as paracoccidioidomycosis, in complicated cases. blastomycosis, aspergillosis, candidiasis The initial treatment of choice for pro- and coccidioidomycosis. The detection gressive disseminated histoplasmosis in of these antibodies is of great value to immunocompromised individuals is lysosomal diagnose meningeal involvement in his- amphotericin B, while itraconazole is used in toplasmosis. The detection of antigens in mild presentations of the disease and as re- progressive disseminated histoplasmosis duction therapy. (4) Primary prophylaxis with is more sensitive than the detection of an- itraconazole (200 mg/day) is recommended tibodies, especially in urine. The detection to reduce the risk of histoplasmosis in HIV-in- of galactomannan antigen by enzyme immu- fected patients with CD4 cell counts <150 noassay is the only commercially available cells/mm3 living in endemic areas. (9) methodology that has been validated and It is worth mentioning that since 1987 approved by the European Community for histoplasmosis has been considered an in vitro diagnosis. (5) AIDS-defining infection because it is the first 3) Histopathological analysis with different manifestation of the syndrome in 50-75% of stains (Wright, Giemsa, Schiff periodic HIV-infected patients; furthermore, dissemi- acid and methenamine silver) is a useful nated infection may occur in 2-5% of them, tool, but can have a sensitivity lower than particularly in patients living in endemic areas. 50%, depending on the experience of the (10) In Latin America, where there are areas of observer since the Histoplama yeasts may high endemicity (Colombia, Argentina, Mexico, be mistaken for Candida spp., Penicillium Brazil, Venezuela, etc.), it has been estimated marneffei, Pneumocystis jirovecii, Crypto- that about 1 600 000 people live with HIV, of coccus neoformans, Blastomyces derma- which 24 000 develop disseminated histoplas- titidis and Leishmania spp., or for artifacts. mosis with a mortality rate of ≥40%. Although 4) Molecular methods, in particular polymerase antiretroviral therapy has helped to reduce the chain reaction (PCR), are a diagnostic alter- incidence of histoplasmosis, it is a fact that in native with suitable sensitivity and specificity Latin America this infection continues to be to detect and identify Histoplasma spp. in a serious health problem, since there are still biological and environmental samples in a many people who do not have access to this rapid manner (6,7); however, their diag- therapy, which, together with the lack of tests nostic use has not been approved by the that would allow a timely diagnosis, increases Food and Drug Administration (FDA). (5,8) the risk of death. (11) With all this in mind, it is evident that histo- All these limitations cause a delay in the plasmosis is a disease of great medical interest diagnosis and subsequent mismanagement of due to its association with the population of patients. For this reason, a multiple approach individuals living with HIV/AIDS and its clinical to diagnosis is recommended, involving epide- similarity with tuberculosis. The public health miological and, especially, working knowledge problem posed by this fungal infection should of the patient, as well as laboratory, radio- be addressed comprehensively, considering that graphic, histopathological, microbiological, it is not a disease that is compulsorily reported case reports Vol. 5 No. 2: 85-8 88 and its real incidence is unknown, reason why mosis. Clin Chest Med. 2017;38(3):403-15. prevention and control programs have not been http://doi.org/c6wq. developed for the population most vulnerable to 6. Buitrago MJ, Canteros CE, Frías-De León G, developing it. It is important that, in the presence González Á, Marques-Evangelista De Oli- of clinical suspicion, physicians have knowledge veira M, Muñoz CO, et al. Comparison of PCR of the set of tests that can be used, as well as protocols for detecting Histoplasma capsulatum of their limitations, in order to confirm the diag- DNA through a multicenter study. Rev Iberoam nosis, provide the most appropriate therapeutic Micol. 2013;30(4):256-60. http://doi.org/f2f28v. management for each patient, and influence the 7. Gómez LF, Torres IP, Jiménez-A MDP, reduction of the mortality rate. McEwen JG, de Bedout C, Peláez CA, et al. Detection of Histoplasma capsulatum in Organic Fertilizers by Hc100 Nested Polymerase Chain REFERENCES Reaction and Its Correlation with the Physicoche- mical and Microbiological Characteristics of the 1. Sepúlveda VE, Márquez R, Turissini DA, Gold- Samples. Am J Trop Med Hyg. 2018;98(5):1303- man WE, Matute DR. Genome sequences reveal 12. http://doi.org/gdnphz. cryptic speciation in the human pathogen Histo- 8. Guarner J. Human immunodeficiency virus plasma capsulatum. MBio. 2017;8(6):e01339-17. and fungal infections. Semin Diagn Pathol. http://doi.org/c7j2. 2017;34(4):325-31. http://doi.org/c7j5. 2. Wheat LJ, Azar MM, Bahr NC, Spec A, Relich 9. Chastain DB, Henao-Martínez AF, Fran- RF, Hage C. Histoplasmosis. Infect Dis Clin Nor- co-Paredes C. Opportunistic invasive mycoses th Am. 2016;30(1):207-27. http://doi.org/f8f9nx. in AIDS: cryptococcosis, histoplasmosis, coc- 3. Bahr NC, Antinori S, Wheat LJ, Sarosi GA. cidiodomycosis,
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