TOPLINE

In a cohort study, relapse was uncommon among immunocompromised patients with histoplasmosis who discontinued antifungal therapy before the guideline-recommended 12 months, occurring in only 6.6% of patients; no deaths during follow-up were attributable to the infection.

METHODOLOGY

• Researchers conducted a retrospective cohort study of immunocompromised adults who received antifungal therapy for histoplasmosis between 2005 and 2025 and had clinical follow-up after treatment discontinuation.
• They included 106 patients (median age at diagnosis, 48 years; 54% men) who were categorized by treatment duration: 78 (74%) received at least 12 months of antifungal therapy (guideline-based duration), and 28 (26%) received less than 12 months of therapy (shorter duration).
• The primary outcome combined several histoplasmosis-related adverse events that occurred after antifungal therapy was discontinued — relapse, hospitalization due to histoplasmosis, or histoplasmosis-related death; secondary outcomes included all-cause adverse events.
• Median duration of follow-up after antifungal discontinuation was 1411 days for patients in the shorter-duration group (treated for < 12 months) and 1348 days for those in the guideline-based duration group (treated for ≥ 12 months.).

TAKEAWAY

• Overall, relapse occurred in seven patients, including 12% (3/25) of those treated for less than 12 months and 5.5% (4/73) of those treated for 12 months or longer. No deaths occurred due to histoplasmosis during follow-up.
• Shorter treatment duration was not associated with a higher risk for histoplasmosis-related outcomes in unadjusted (hazard ratio [HR], 2.27) or adjusted (HR, 2.34; P = .27) analyses. 
• All-cause adverse events were more common with shorter treatment: rehospitalization occurred in 80% of patients treated for less than 12 months vs 52.1% of those treated 12 months or longer (odds ratio [OR], 3.64; P = .018); death rates were similar between groups (20% vs 23.3%; P = .734).
• Patients with antigen levels of 10.1-20 ng/mL at diagnosis had significantly lower odds of histoplasmosis-related adverse events than those with levels > 20 ng/mL (OR, 0.02; P = .046).

IN PRACTICE

"[R]elapse after antifungal discontinuation was uncommon in this cohort of immunocompromised patients with histoplasmosis, though this study was underpowered to reveal an increase in risk with shorter treatment duration. Baseline disease burden, as reflected by antigen levels and timing of diagnosis, appeared to influence post-treatment outcomes," the authors of the study wrote.

SOURCE

The study was led by Caden Tuinstra, Indiana University School of Medicine, Indianapolis. It was published online on September 12, 2026, in Open Forum Infectious Diseases.

LIMITATIONS

Inclusion of only those patients who survived initial infection and had follow-up after treatment discontinuation may have underestimated true relapse risk. Treatment duration was determined by clinicians rather than randomization, which may have introduced confounding by indication. Additionally, few histoplasmosis-related events limited statistical power.

DISCLOSURES

Tuinstra was supported by the Health Resources and Services Administration of the US Department of Health and Human Services as part of a scholarship award. One author declared serving as a medical advisor for MiraVista Diagnostics. Other authors reported no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.