Noteworthy features of coccidioidomycosis include eosinophilia, meningitis and a syndrome of weight loss and fever without focal disease. Although in the pre-HAART era coccidioidomycosis most often presented as disseminated or extensive pulmonary disease, and rarely presented as an asymptomatic infection, in the post-HAART era there has been increasing recognition of cases that are asymptomatic, which are detected with just a positive serological test or by an incidental nodule or cavity on chest radiograph . These cases are associated with an
undetectable HIV-1 viral load on HAART and with a mean CD4 T-cell count of >350 cells/μL. In disseminated disease cultures of bone marrow are frequently positive (category III recommendation). Definitive diagnosis involves culture of the organism from sputum, broncho-alveolar lavage (BAL) or a biopsy Selleckchem Galunisertib specimen – which can take up to 4 weeks for growth – or identification of the yeast on a biopsy specimen or body fluid [66,67,70]. Each yeast has a characteristic appearance on biopsy. In disseminated disease, cultures of Panobinostat bone marrow are frequently positive and blood cultures may also be diagnostic . A polysaccharide antigen test for H. capsulatum var capsulatum is available and is particularly useful in
patients with disseminated disease  or in BAL specimens with pulmonary disease  but its availability is largely limited to a US reference laboratory. Serology is positive in approximately 70% of cases with coccidioidomycosis . Patients with disseminated histoplasmosis may have very high LDH levels (>600 IU/L) . Diagnosis of CNS disease may be difficult as fungal stains, culture and even serological tests may all be negative. Real-time PCR assays seem to be very useful (up to 100% pick-up rate) , but are not yet widely available. Localized disease should be treated initially as for HIV-seronegative individuals with itraconazole solution for histoplasmosis/blastomycosis and fluconazole for coccidioidomycosis (category IV recommendation). For localized histoplasmosis or blastomycosis treatment is with itraconazole 200 mg bd, administered much as the oral solution due to better bioavailability,
and with therapeutic monitoring to check levels due to variability between individuals . This recommendation represents an extrapolation of data and guidelines intended for HIV-seronegative individuals but seems appropriate for the less immunocompromised individuals who present with this form of disease (category IV recommendation). For C. immitis fluconazole 400–800 mg od is the preferred azole (category IV recommendation) . Itraconazole 200 mg bd po (with a loading dose of 200 mg tid/300 mg bd for 3 days) can also be used for initial treatment of mild disseminated histoplasmosis in HIV-seropositive individuals . Important interactions occur between itraconazole (and other azoles) and HAART (Table 7.1 in 7. Candidiasis).