Among people with HIV, histoplasmosis represents an important cause of mortality. Previous studies have provided estimates of the disease incidence. Here, we compared those estimates with the results obtained from a screening program implemented in Guatemala, which included histoplasmosis detection for people with HIV. To compare the results of this program, with previous estimations, a literature search was done and reports about histoplasmosis incidence were analyzed. The screening program enrolled 6,366 patients. The overall histoplasmosis incidence in the screening program was 7.4%, which was almost double than those estimated by the previous studies. From 2017 to 2019, the screening program showed an upward trend in histoplasmosis cases from 6.5% to 8.8%. Histoplasmosis overall mortality among those who were newly HIV diagnosed showed a decrease at 180 days from 32.8% in 2017 to 21.2% in 2019. The screening approach using rapid diagnostic assays detects quickly more cases of histoplasmosis, allowing a specific treatment, which decreases the mortality of the disease. Therefore, the use of these new techniques, especially in endemic areas of histoplasmosis, must be implemented.

Histoplasmosis is one of the most underdiagnosed and underreported endemic mycoses in the United States. Histoplasma capsulatum is the causative agent of this disease. To date, molecular epidemiologic studies detailing the phylogeographic structure of H. capsulatum in the United States have been limited. We conducted genomic sequencing using isolates from histoplasmosis cases reported in the United States. We identified North American Clade 2 (NAm2) as the most prevalent clade in the country. Despite high intra-clade diversity, isolates from Minnesota and Michigan cases predominately clustered by state. Future work incorporating environmental sampling and veterinary surveillance may further elucidate the molecular epidemiology of H. capsulatum in the United States and how genomic sequencing can be applied for surveillance and outbreak investigation of histoplasmosis.

Histoplasmosis is a systemic mycosis of universal distribution, highly endemic in the Americas. It is caused by a dimorphic fungus Histoplasma capsulatum var. capsulatum. It affects both immunocompetent and immunocompromised individuals where progressive and disseminated forms are observed. A very important risk factor is HIV infection/AIDS, with a mortality rate of 20-40% in Latin America. The diagnosis of this mycosis is made by conventional and molecular methods or by antigen and antibody detection. This study evaluated the sensitivity and specificity of a commercial kit for the detection of Histoplasma antigen by an EIA (HC-Ag) technique in 50 patients with histoplasmosis associated with AIDS. In addition, its performance was compared with that of other diagnostic techniques routinely used in our laboratory. HC-Ag had a sensitivity (S) of 94%, specificity (E) 95.5%, positive predictive value (PPV) 94% and negative predictive value (NPV) 95.5%. The delay time of the results was 4 days, similar to that of antibody detection and n-PCR and much less than that of blood cultures. The combination of methods improved S and NPV: 100%; with similar values in E and PPV. The HC-Ag method demonstrated its usefulness in the diagnosis of progressive disseminated histoplasmosis and the combination of methods is a good option to increase sensitivity and decrease the time to reach the diagnosis of certainty. This allows improving the strategy in the management of the disease and decreasing its case-fatality rate.

Background: Histoplasmosis is a systemic mycosis, present globally. We aimed to describe cases of histoplasmosis (Hc) and to establish a risk profile associated to Hc in HIV-infected patients (HIV+). Methods: This was a retrospective study of patients with a clinical-. laboratorial diagnosis of Hc. Data was fed into REDCap and statistical analysis was done with R . Results: We included 99 records, 65 HIV+ and 34 HIV-. Average age was 39 years. Median time from onset to diagnosis was 8 weeks in HIV- and 22 weeks in HIV+. Disseminated histoplasmosis occurred in 79.4% HIV+, vs 36.4% HIV-. Median CD4 count was 70. Co-infection with tuberculosis was present in 20% of HIV+. Blood cultures were positive in 32.3% of HIV+ vs 11.8% of HIV- (p=0.025); bone marrow culture was positive in 36.9% vs 8.8%(p=0.003). Most HIV+ patients (71.4%) were hospitalized. On univariate analysis, anemia, leukopenia, intensive care, use of vasopressors and mechanical ventilation were associated with death in HIV+. Conclusions: Most of our patients with histoplasmosis were HIV+, presenting advanced AIDS. Diagnosis was late in HIV+ patients, and they frequently presented disseminated Hc, required hospitalization, and died. Early screening for Hc in HIV+ and drug induced immunosuppressed patients is crucial.

Heat shock proteins (Hsps) are highly conserved molecules that are constitutively expressed and upregulated in response to physiological stress conditions. These immunogenic chaperones can have essential functions in fungi, particularly in dimorphic pathogens. Histoplasma capsulatum and Paracoccidioides species are dimorphic fungi that are the causative agents of histoplasmosis and paracoccidioidomycosis, respectively, which are systemic mycoses with significant rates of morbidity and mortality. Current treatment consists of long-term antifungal agents, and there is an urgent need for new therapeutic approaches with higher efficacy, lower toxicity, better biodistribution and improved selectivity. We engineered an immunoglobulin G1 (IgG1) isotype chimeric mouse-human monoclonal antibody, titled ch-MAb 4E12, from the parental IgG2a MAb 4E12, a monoclonal antibody to H. capsulatum Hsp60 that is protective in experimental histoplasmosis and paracoccidioidomycosis models elicited by H. capsulatum var. capsulatum and Paracoccidioides lutzii, respectively. The ch-MAb 4E12 increased phagolysosomal fusion and enhanced the yeasts uptake by PMA differentiated human THP1 macrophage cells in vitro. At low concentrations, the chimeric antibody significantly reduced the pulmonary and splenic fungal burden compared to an irrelevant antibody or no treatment. These results are the first to show that a chimeric mouse-human antibody can modify infection caused by dimorphic fungi.