Diagnosis and treatment of histoplasmosis in HIV-infected patients
- John W Baddley, MD, MSPH
John W Baddley, MD, MSPH
- Professor of Medicine
- Birmingham VA Medical Center
- University of Alabama at Birmingham
Histoplasmosis is an important infectious disease among patients with AIDS and continues to cause severe morbidity and mortality in endemic areas, particularly in resource-limited settings [1,2].
The diagnosis and treatment of histoplasmosis will be discussed here. The epidemiology and clinical manifestations of infection are discussed elsewhere. (See "Epidemiology and clinical manifestations of histoplasmosis in HIV-infected patients".)
There are multiple diagnostic tests for disseminated H. capsulatum infection, including culture, serology, antigen testing, and direct microscopy; the diagnostic yield will depend on the stage of disease. Since most AIDS patients have disseminated disease, the most sensitive and specific test is detection of histoplasma antigen .
When resources are limited, the simplest and least expensive test (although not definitive) is direct microscopy of budding yeast within tissues or body fluids. The combination of culture with direct microscopy increases the diagnostic yield.
Timely diagnosis requires a high index of clinical suspicion. The advantages and disadvantages of these methods for diagnosis of histoplasmosis in the HIV-infected patient are discussed below. Additional information on diagnostic testing for histoplasmosis can also be found elsewhere. (See "Diagnosis and treatment of disseminated histoplasmosis in HIV-uninfected patients".)
- Panel on Opportunistic Infections in HIV-Infected Adults and Adolescents. Guidelines for the prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: Recommendations from the Centers for Disease Control and Prevention, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. http://aidsinfo.nih.gov/contentfiles/lvguidelines/adult_oi.pdf (Accessed on November 04, 2015).
- Baddley JW, Sankara IR, Rodriquez JM, et al. Histoplasmosis in HIV-infected patients in a southern regional medical center: poor prognosis in the era of highly active antiretroviral therapy. Diagn Microbiol Infect Dis 2008; 62:151.
- Hage CA, Ribes JA, Wengenack NL, et al. A multicenter evaluation of tests for diagnosis of histoplasmosis. Clin Infect Dis 2011; 53:448.
- Wheat LJ, Connolly-Stringfield PA, Baker RL, et al. Disseminated histoplasmosis in the acquired immune deficiency syndrome: clinical findings, diagnosis and treatment, and review of the literature. Medicine (Baltimore) 1990; 69:361.
- Couppié P, Aznar C, Carme B, Nacher M. American histoplasmosis in developing countries with a special focus on patients with HIV: diagnosis, treatment, and prognosis. Curr Opin Infect Dis 2006; 19:443.
- Arango-Bustamante K, Restrepo A, Cano LE, et al. Diagnostic value of culture and serological tests in the diagnosis of histoplasmosis in HIV and non-HIV Colombian patients. Am J Trop Med Hyg 2013; 89:937.
- Prechter GC, Prakash UB. Bronchoscopy in the diagnosis of pulmonary histoplasmosis. Chest 1989; 95:1033.
- Nightingale SD, Parks JM, Pounders SM, et al. Disseminated histoplasmosis in patients with AIDS. South Med J 1990; 83:624.
- Akpek G, Lee SM, Gagnon DR, et al. Bone marrow aspiration, biopsy, and culture in the evaluation of HIV-infected patients for invasive mycobacteria and histoplasma infections. Am J Hematol 2001; 67:100.
- Wheat LJ, Freifeld AG, Kleiman MB, et al. Clinical practice guidelines for the management of patients with histoplasmosis: 2007 update by the Infectious Diseases Society of America. Clin Infect Dis 2007; 45:807.
- Wheat LJ, Connolly-Stringfield P, Blair R, et al. Histoplasmosis relapse in patients with AIDS: detection using Histoplasma capsulatum variety capsulatum antigen levels. Ann Intern Med 1991; 115:936.
- Hajjeh RA. Disseminated histoplasmosis in persons infected with human immunodeficiency virus. Clin Infect Dis 1995; 21 Suppl 1:S108.
- Edwards LB, Acquaviva FA, Livesay VT, et al. An atlas of sensitivity to tuberculin, PPD-B, and histoplasmin in the United States. Am Rev Respir Dis 1969; 99:Suppl:1.
- Gascón J, Torres JM, Jiménez M, et al. Histoplasmosis infection in Spanish travelers to Latin America. Eur J Clin Microbiol Infect Dis 2005; 24:839.
- Wheat J, MaWhinney S, Hafner R, et al. Treatment of histoplasmosis with fluconazole in patients with acquired immunodeficiency syndrome. National Institute of Allergy and Infectious Diseases Acquired Immunodeficiency Syndrome Clinical Trials Group and Mycoses Study Group. Am J Med 1997; 103:223.
- Lanternier F, Lortholary O. Liposomal amphotericin B: what is its role in 2008? Clin Microbiol Infect 2008; 14 Suppl 4:71.
- Wheat J, Hafner R, Korzun AH, et al. Itraconazole treatment of disseminated histoplasmosis in patients with the acquired immunodeficiency syndrome. AIDS Clinical Trial Group. Am J Med 1995; 98:336.
- Wheat LJ, Connolly P, Haddad N, et al. Antigen clearance during treatment of disseminated histoplasmosis with itraconazole versus fluconazole in patients with AIDS. Antimicrob Agents Chemother 2002; 46:248.
- Sarosi GA, Johnson PC. Disseminated histoplasmosis in patients infected with human immunodeficiency virus. Clin Infect Dis 1992; 14 Suppl 1:S60.
- Hostetler JS, Denning DW, Stevens DA. US experience with itraconazole in Aspergillus, Cryptococcus and Histoplasma infections in the immunocompromised host. Chemotherapy 1992; 38 Suppl 1:12.
- Brooks JT, Wheat LJ. Histoplasmosis: update 1998. AIDS Clin Care 1998; 10:4.
- Wheat LJ, Connolly P, Smedema M, et al. Emergence of resistance to fluconazole as a cause of failure during treatment of histoplasmosis in patients with acquired immunodeficiency disease syndrome. Clin Infect Dis 2001; 33:1910.
- Johnson PC, Wheat LJ, Cloud GA, et al. Safety and efficacy of liposomal amphotericin B compared with conventional amphotericin B for induction therapy of histoplasmosis in patients with AIDS. Ann Intern Med 2002; 137:105.
- Wheat J. Histoplasmosis. Experience during outbreaks in Indianapolis and review of the literature. Medicine (Baltimore) 1997; 76:339.
- Dismukes WE, Bradsher RW Jr, Cloud GC, et al. Itraconazole therapy for blastomycosis and histoplasmosis. NIAID Mycoses Study Group. Am J Med 1992; 93:489.
- Pitisuttithum P, Negroni R, Graybill JR, et al. Activity of posaconazole in the treatment of central nervous system fungal infections. J Antimicrob Chemother 2005; 56:745.
- Wheat LJ, Connolly-Stringfield P, Williams B, et al. 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 1992; 145:1421.
- Huet E, Hadji C, Hulin A, et al. Therapeutic monitoring is necessary for the association itraconazole and efavirenz in a patient with AIDS and disseminated histoplasmosis. AIDS 2008; 22:1885.
- Koo HL, Hamill RJ, Andrade RA. Drug-drug interaction between itraconazole and efavirenz in a patient with AIDS and disseminated histoplasmosis. Clin Infect Dis 2007; 45:e77.
- Breton G, Adle-Biassette H, Therby A, et al. Immune reconstitution inflammatory syndrome in HIV-infected patients with disseminated histoplasmosis. AIDS 2006; 20:119.
- Tobón AM, Agudelo CA, Rosero DS, 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 2005; 73:576.
- Huber F, Nacher M, Aznar C, et al. AIDS-related Histoplasma capsulatum var. capsulatum infection: 25 years experience of French Guiana. AIDS 2008; 22:1047.
- Adenis A, Nacher M, Hanf M, et al. HIV-associated histoplasmosis early mortality and incidence trends: from neglect to priority. PLoS Negl Trop Dis 2014; 8:e3100.
- Daher EF, Silva GB Jr, Barros FA, et al. Clinical and laboratory features of disseminated histoplasmosis in HIV patients from Brazil. Trop Med Int Health 2007; 12:1108.
- Antinori S, Magni C, Nebuloni M, et al. Histoplasmosis among human immunodeficiency virus-infected people in Europe: report of 4 cases and review of the literature. Medicine (Baltimore) 2006; 85:22.
- Drew RH. Pharmacotherapy of disseminated histoplasmosis in patients with AIDS. Ann Pharmacother 1993; 27:1510.
- McKinsey DS, Gupta MR, Riddler SA, et al. Long-term amphotericin B therapy for disseminated histoplasmosis in patients with the acquired immunodeficiency syndrome (AIDS). Ann Intern Med 1989; 111:655.
- Hecht FM, Wheat J, Korzun AH, et al. Itraconazole maintenance treatment for histoplasmosis in AIDS: a prospective, multicenter trial. J Acquir Immune Defic Syndr Hum Retrovirol 1997; 16:100.
- Goldman M, Zackin R, Fichtenbaum CJ, et al. Safety of discontinuation of maintenance therapy for disseminated histoplasmosis after immunologic response to antiretroviral therapy. Clin Infect Dis 2004; 38:1485.
- Myint T, Anderson AM, Sanchez A, et al. Histoplasmosis in patients with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS): multicenter study of outcomes and factors associated with relapse. Medicine (Baltimore) 2014; 93:11.
- McKinsey DS, Wheat LJ, Cloud GA, et al. Itraconazole prophylaxis for fungal infections in patients with advanced human immunodeficiency virus infection: randomized, placebo-controlled, double-blind study. National Institute of Allergy and Infectious Diseases Mycoses Study Group. Clin Infect Dis 1999; 28:1049.
- Antigen detection
- Direct microscopy
- Skin testing
- DIFFERENTIAL DIAGNOSIS
- Antifungal agents
- - Amphotericin B
- - Itraconazole
- - Fluconazole
- - Other agents
- Moderately severe to severe disease
- Mild to moderate disease
- DRUG INTERACTIONS
- DURATION OF THERAPY
- MONITORING OF PATIENTS
- IMMUNE RECONSTITUTION
- MORBIDITY AND MORTALITY
- Prognostic factors
- SUPPRESSIVE THERAPY
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS