Histoplasmosis

The purpose of the study is threefold: 1. Assess the safety and efficacy of a single high-dose intravenous (LAmB 10mg/kg) compared to the SOC daily dosing (3mg/kg) of the same medication for induction therapy in moderate to severe histoplasmosis. 2. Assess the safety and efficacy of oral posaconazole 300mg delayed-release tablets three times daily for two days then once daily for consolidation therapy compared to SOC oral itraconazole 200 mg capsules three times daily for three days then twice daily in moderate to severe histoplasmosis 3. Assess the safety and efficacy of 6 months of consolidation therapy compared to the SOC 12 months of consolidation therapy in persons with HIV on appropriate antiretroviral therapy.

The prison system in French Guiana is characterized by severe overcrowding, high levels of promiscuity, poor sanitary conditions, and the documented presence of potential reservoirs or vectors of zoonotic diseases, particularly swallows and rodents. In French Guiana, several zoonotic diseases have a high incidence or are of particular public health significance, including Q fever, leptospirosis, Chagas disease, histoplasmosis, and toxoplasmosis. Despite this context, the risk of zoonotic diseases in prisons remains poorly documented, even though endemic and epidemic circulation of Q fever has already been described at the French Guiana correctional facility. This study aims to document this risk in a systematic and prospective manner. The main objective is to assess the prevalence of zoonotic infections (Q fever, leptospirosis, Chagas disease, histoplasmosis, and toxoplasmosis) among inmates at the French Guiana Correctional Facility in 2026-2027. The other objectives are : * To measure the seroprevalence of zoonotic infections among new arrivals at the French Guiana correctional facility; * To identify individual risk factors, both within and outside the prison, for acquiring zoonotic infections; * To analyze the results in relation to bioclimatic data (wind direction, humidity, precipitation, temperature) The expected benefits will aim to objectively assess the risk of zoonotic diseases within the French Guiana correctional facility, to improve understanding of zoonoses in prison settings, to guide the implementation of appropriate prevention and screening measures, and to contribute to improving health conditions in detention. It should also strengthen cooperation between health and justice officials as part of an integrated approach to the prevention and management of infectious diseases.

This Phase II platform trial will evaluate the safety, tolerability, and effectiveness of investigational antifungal agents as salvage or consolidation therapy in adults with dimorphic fungal infections, including coccidioidomycosis, blastomycosis, and histoplasmosis. The study will enroll adults who are receiving active antifungal therapy and who have intolerance, failure, or unavailability of standard first-line consolidation therapy. The first investigational agent evaluated in the platform trial is oteseconazole. Participants will receive study drug and complete follow-up assessments for symptom status, functional status, adverse events, laboratory safety, study drug discontinuation, and quality of life. Participants will be followed during therapy and for up to 6 months after therapy.