Diagnosis and treatment of histoplasmosis

A method of treating a subject who has histoplasmosis, the method comprising:

• obtaining a sample comprising breath of a subject or headspace from a culture suspected of comprising Histoplasma capsulatum isolated from a subject;
• detecting the presence in the sample one, two, or all three VOCs selected from the group consisting of cyperene, 1R,4aR,8aR)-2,5,5,8a-Tetramethyl-4,5,6,7,8,8a-hexahydro-1H-1, 4a-methanonaphthalene, and viridiflorol;
• and
• administering an antifungal treatment to a subject who has one, two, or all three VOCs selected from the group consisting of cyperene, 1R,4aR,8aR)-2,5,5,8a-Tetramethyl-4, 5,6,7,8,8a-hexahydro-1H-1,4a-methanonaphthalene, and viridiflorol.

A method of monitoring efficacy of a treatment for histoplasmosis in a subject, the method comprising:

• determining a first level of one, two, or all three volatile organic compounds (VOCs) produced by Histoplasma capsulatum in a sample comprising breath from the subject or headspace from a culture suspected of comprising Histoplasma capsulatum isolated from the subject, wherein the VOCs are selected from the group consisting of cyperene, 1R,4aR,8aR)-2,5,5,8a-Tetramethyl-4,5,6,7,8,8a-hexahydro-1H-1, 4a-methanonaphthalene, and viridiflorol, in the subject;
• administering a treatment for histoplasmosis to the subject;
• determining a second level of the VOCs in a sample obtained after administration of the treatment to the subject;
• and
• comparing the first and second levels of VOCs, wherein a decrease in the VOCs indicates that the treatment has been effective in treating the histoplasmosis in the subject, and an increase or no change indicates that the treatment has not been effective in treating the histoplasmosis in the subject.

A method of identifying a candidate compound for the treatment of histoplasmosis, the method comprising:

• providing a test culture comprising Histoplasma capsulatum;
• detecting a baseline level of fungal VOCs in the headspace of the culture in the absence of the test compound, wherein the VOCs are selected from the group consisting of cyperene, 1R,4aR,8aR)-2,5,5,8a-Tetramethyl-4,5,6,7,8,8a-hexahydro-1H-1, 4a-methanonaphthalene, and viridiflorol, in the subject;
• contacting the test culture with a test compound;
• determining a second level of the VOCs in a the test culture;
• comparing the second level of VOCs to the baseline level;
• and
• identifying a test compound that decreases levels of fungal VOCs in the test culture as a candidate compound for the treatment of histoplasmosis.