A comparison of presentations and outcomes of histoplasmosis across patients with varying immune status

Abstract

Few large cohorts have examined histoplasmosis in both immunocompromised and immunocompetent patients. We describe the differences in presentations and outcomes of histoplasmosis by immune and dissemination status. We assembled a retrospective cohort of adult patients diagnosed with histoplasmosis from 2002 to 2017. Patients were grouped by immune status: people living with HIV (PLWH), patients who were HIV negative but had other-immunocompromise (OIC), and immunocompetent patients. Patients were further classified into asymptomatic lung nodule (ALN), localized and disseminated disease groups, and outcomes were compared across patients by these immune status categories We identified 261 patients with histoplasmosis: 54 (21%) PLWH, 98 (38%) OIC, and 109 (42%) immunocompetent. Disseminated disease was more common among PLWH than among other groups (P < .001). In localized disease, median time from symptom onset to diagnosis was longer in immunocompetent patients than in other groups (P = .012), and was not significant in disseminated disease. The 90-day mortality was higher in PLWH (25%) and OIC (26%) with localized disease compared to the immunocompetent group (4%) (P = .009), but this difference was not seen in disseminated disease. Patients with localized disease had lower 90-day mortality (14%) compared to those with disseminated disease (21%) (P = .034). We conclude that immunocompetent individuals present with fewer typical symptoms, laboratory findings, and radiographic features of Histoplasma infection, leading to potential delays in diagnosis in this group. Despite this, immunocompetent patients have lower 90-day mortality in localized disease, and do not experience increased 90-day mortality in disseminated disease. Lay Summary This article examines how the signs and symptoms of histoplasmosis vary by immune status and dissemination status. Immunocompetent patients with localized disease present with fewer typical signs and symptoms, are diagnosed later, but despite this have lower 90-day mortality.

Histoplasmosis Diagnosed in Europe and Israel: A Case Report and Systematic Review of the Literature from 2005 to 2020

“…This last prevalence is in line with the 8% found in a recent systematic review of acute histoplasmosis in immunocompetent travellers [9]. One recent retrospective study of 261 cases conducted in the United States found similar prevalence of disseminated disease among PLWH (78%) and patients with OIC (58%), but a higher prevalence among immunocompetent subjects (33%) [154]. As the exposure of the majority of the immunocompetent patients considered in our review was limited to travel, it can be speculated that the higher rate of disseminated disease in the American review may have been due to greater inoculum exposure.…”

“…Sixty percent of the immunocompetent subjects with acute pulmonary histoplasmosis were apparently successfully treated with itraconazole. It is difficult to evaluate clinical outcomes on the basis of single case reports and small case series, but mortality rates in the different categories of patients (PLWH 24.1%; patients with OIC 32%; and immunocompetent patients 5.6%) were sufficiently similar to those reported by Franklin et al in the USA (15%; 24%, and 13%, respectively) [154].…”

Closing gaps in histoplasmosis: clinical characteristics and factors associated with probable/histoplasmosis in HIV/AIDS hospitalized patients, a retrospective cross-sectional study in two tertiary centers in Pereira, Colombia

“…Histoplasmosis is a common opportunistic infection in hospitalized PLWH and is associated with high mortality [ 1 , 2 , 20 , 21 ]. The risk factors for Probable/Histoplasmosis were pancytopenia, < 50 CD4 + cells/μL and high AST levels.…”

Frequency and Duration of, and Risk Factors for, Diagnostic Delays Associated with Histoplasmosis

“…Difficulty diagnosing histoplasmosis can lead to delays in treatment. Failure to treat moderate-to-severe cases of histoplasmosis contributes to adverse outcomes ranging from prolonged symptoms to hospitalization and death [ 25 ]. In this paper, we estimate the incidence of diagnostic delays associated with histoplasmosis, estimate the average length of delays associated with histoplasmosis, and identify specific risk factors for diagnostic delays.…”