<p>HIV-Associated Histoplasmosis: Current Perspectives</p>

Abstract

Histoplasmosis is an endemic mycosis caused by Histoplasma capsulatum. Infection develops by inhalation of microconidia from environmental sites inhabited by birds and bats. Disseminated disease is the usual presentation due to impaired cellular immunity. Common clinical manifestations include fever, fatigue, malaise, anorexia, weight loss, and respiratory symptoms. Histoplasma antigen detection is the most sensitive method for diagnosis. The sensitivity of the MVista ® Quantitative Histoplasma antigen enzyme immunoassay is 95-100% in urine, over 90% in serum and bronchoalveolar lavage (BAL) antigen and 78% in cerebral spinal fluid (CSF). A proven diagnosis can be established by culture or pathology with sensitivities between 70% and 80%. The sensitivity of antibody detection by immunodiffusion or complement fixation was between 60% and 70%. Diagnosis using molecular methods has not been adequately validated for implementation and FDA cleared assays are unavailable. Liposomal amphotericin B should be used for 1-2 weeks followed by itraconazole for at least one year until CD4 counts are above 150 cells/mm3, HIV viral load is below 400 copies/mL and Histoplasma urine antigen is negative. Serum itraconazole level should be monitored to avoid drug toxicity. Antigen should be measured periodically to establish that treatment is effective and to assist in identifying relapse. The incidence of immune reconstitution inflammatory syndrome is low but it must be considered in patients who are thought to be failing antifungal treatment as it does not respond to changing antifungal agents but rather to initiation of corticosteroid therapy. In this review, we discuss pathogenesis, clinical manifestations, diagnosis and treatment based on personal experience and relevant publications.

Laboratory Diagnosis of Histoplasmosis: An Update

“…However, false positive and negative results still occurred due to cross-reactivity with other endemic fungi and antibiotic treatment, respectively, and a pre-treatment step was required extending turnaround times. Currently, a new LFD test is being developed and validated by using urine samples [35].…”

“…Another approach in constant development is based on determining host and fungal biomarkers that could indicate the presence of H. capsulatum in human body fluids. Recent advances in antibody detection are related to the refinement of antibody detection platforms (Histoplasma antibody IgG IgM EIA, MiraVista Diagnostics), while most efforts in antigen detection are focused on improving diagnostic yields of POC methods [35].…”

Introductory Chapter: The Global Distribution of Human Histoplasmosis - An Overview

“…Individuals whose cellular immunity is compromised for number of reasons for example HIV infection, organ transplant, immunosuppressive therapy or biological therapy, i.e., anti-TNF-α drugs usually present with a disseminated form of histoplasmosis [10,11,43]. Disseminated histoplasmosis presents with fever, fatigue, malaise, anorexia, weight loss, and respiratory symptoms [1,5].…”

“…Focal or diffuse multi-organ is typical, with predilection for the reticuloendothelial system and the central nervous system. Physical examinations may reveal painful oropharyngeal ulceration, hepato-splenomegaly, and diffuse lymphadenopathy [5,10,17,44].…”

“…Humans acquire histoplasmosis through inhalation of Histoplasma microconidia (spores) from abiotic environment. Majority of the immunocompetent individuals are asymptomatic, some develop self-limiting influenza-like syndromes and a vast minority develop disseminated disease, especially those with severe immunosuppression such as those with HIV/AIDS and those on biologic therapy [10,11]. Subclinical infections can be demonstrated through histoplasmin skin testing while clinical disease through conventional culture and microscopy or histopathological analysis of the appropriate clinical specimen [12][13][14].…”