Advances in Histoplasma and Histoplasmosis

Dear Colleagues,

In 2022, the World Health Organization classified Histoplasma spp. as a high priority fungal pathogen. The genus includes Histoplasma capsulatum var capsulatum, and Histoplasma capsulatum var duboisii, the agent of African histoplasmosis, as well as additional cryptic species. Histoplasmosis has a global distribution so that the label “endemic mycosis” may no longer be applicable. Discrete areas with high environmental concentrations of H. capsulatum (microfoci) exist both within and outside traditional areas of endemicity. Infection leads to disease in only a small fraction of exposed people, and many people with acute pulmonary histoplasmosis recover spontaneously. Lack of diagnostic modalities in some parts of the world, lack of recognition on the part of healthcare providers, and the occurrence of subclinical infection contributes to underdiagnosis and underreporting of histoplasmosis. People with pulmonary histoplasmosis are often misdiagnosed as having bacterial pneumonia, leading to overuse of antibiotics, higher healthcare costs, and adverse outcomes. Therefore, the Center for Disease Control and Prevention has provided guidance regarding testing for histoplasmosis in patients with community-acquired pneumonia.

The pool of people with an increased risk for disseminated histoplasmosis—including solid organ transplant recipients, stem cell transplant recipients, and people receiving biologics for rheumatologic, dermatologic, and gastrointestinal diseases—continues to grow. AIDS remains a major predisposing condition for people with disseminated histoplasmosis in North America, Latin America, sub-Saharan Africa, and parts of Asia. Disseminated histoplasmosis can affect any organ system, and varied clinical presentations may mimic other diseases. Histoplasma antigen testing allows relatively rapid diagnosis, but this testing modality is not universally available. When available, liposomal amphotericin B is the initial treatment of choice for people with severe histoplasmosis, while the azole of choice for step-down therapy and the initial treatment of milder disease is itraconazole. For people who are unable to take or absorb itraconazole, alternative azoles have been used for salvage therapy, but comparative data are lacking. Olorofim, an orotomide antifungal, has in vitro activity against Histoplasma.

This Special Issue aims to present and disseminate the most recent advances related to Histoplasma spp. and histoplasmosis. Topics of interest for publication include, but are not limited to, the following:

1. Reports of autochthonous cases and outbreaks of histoplasmosis in areas previously not known to be endemic;
2. Whole genome sequencing and phylogenetic analysis of Histoplasma isolates;
3. Identification of specific immunologic deficiencies that are associated with increased risk of histoplasmosis;
4. The risks and costs associated with delayed diagnosis of pulmonary histoplasmosis, and the impact of implementing CDC guidelines for when to test for histoplasmosis in patients with community-acquired pneumonia;
5. Implementation of newer, more accessible diagnostic tests with short turnaround times;
6. Advances in molecular diagnostic testing;
7. Screening for histoplasmosis in people with AIDS;
8. Complications of disseminated histoplasmosis;
9. Use of single, high-dose liposomal amphotericin B for induction therapy for people with severe histoplasmosis;
10. Treatment of histoplasmosis with alternative azoles, such as voriconazole, posaconazole, and isavuconazole, or olorofim;
11. Antifungal drug resistance in Histoplasma spp.;
12. The role of serial Histoplasma antigen testing in people being treated for histoplasmosis;
13. Therapeutic drug monitoring for people being treated with azole antifungals

Dr. Michael Saccente
Guest Editor

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