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precipitation IgM antibodies detected within the first 3 weeks of symptoms, and this will decline to <5% after 7 months from the onset of a self-limiting illness (Galgiani & Thompson, 2016). Therefore, presence of IgM can be used to detect a current


or recent infection. Most IgG tests are based on compliment fixing antibodies involving chitinase, a protein enzyme important in the structure of the fungal cell wall and these


antibodies will persist beyond disease resolution. Compliment fixation antibodies can be detected in other body fluids including cerebrospinal fluid, which is important for the diagnosis of coccidioidal meningitis. Compliment fixation results are expressed as titres, such as 1:4 or 1:64, and indicate the greatest dilution of serum at which complement consumption is still detected. Higher titres reflect more extensive coccidioidal infection, and rising titres are associated with worsening disease. Therefore, serial determinations of complement fixation titres are of prognostic value in human patients (Galgiani & Thompson, 2016). Immunodiffusion tests and enzyme-linked immunoassays


(ELISA) to detect IgG and IgM antibodies are also available as commercially prepared kits. Positive ELISA results are highly sensitive for coccidioidal infection, however, false-positive results have been noted with the IgM ELISA test (Galgiani & Thompson, 2016). Latex tests for coccidioidal antibodies are also commercially available and are attractive to clinical laboratories because of their ease of use and rapidity of obtaining results. However, false-positive reactions occur and positive samples should be retested using other more specific tests (Galgiani & Thompson, 2016). Negative serologies do not exclude the diagnosis of coccidioidomycosis, therefore culture may be required for early diagnosis in some patients. In acute serious human illness, cultures are recommended, but generally serology is sufficient (Galgiani & Thompson, 2016). Coccidioides spp. grow well on most mycologic and


bacteriologic media with a white (nonpigmented) mould typically apparent within 4–7 days of incubation. However, morphologic appearance is not reliable to diagnose Coccidioides spp. Culture containers should only be opened in an appropriate biocontainment cabinet, as cultures during growth phase are infectious if not properly handled. Confirmation of diagnosis is usually by specific DNA sequence using a commercially available DNA probe from the cultured inoculum, which may need to be performed at a reference laboratory (Galgiani & Thompson, 2016). It is not uncommon for human patients with persistent


respiratory disease to receive empiric antibiotics prior to a diagnosis of coccidioides. In one study, 81% of human patients with Valley Fever pneumonia received at least one course, and 31% received multiple courses of antibacterials. Therefore, early serological testing can reduce unnecessary antibacterial therapies, reducing costs, adverse events and antibiotic resistance in the community. Unfortunately, due to cutaneous or rheumatologic conditions that can accompany coccidioidal infections in human patients, corticosteroids are sometimes inadvertently prescribed. Corticosteroids may impede host defences, and their use in patients with coccidioidal infections is contraindicated (Galgiani et al., 2016; Galgiani & Thompson, 2016). Serum antibodies are detected rarely in healthy horses


(Higgins et al., 2005b). Higher serological antibody titres are associated with a poorer prognosis for survival (Higgins et al., 2007). Horses with disseminated disease and pneumonia with


thoracic effusion usually have severe clinical disease and frequently die (19 of 21 cases) (Higgins et al., 2007). The donkey in the associated case report had osteomyelitis and subcutaneous infection. Microbiologic culture of a draining tract grew only Pseudomonas aeruginosa, but coccidioides AGID assay was IgM and IgG antibody positive and the immunodiffusion titre was ≥1:256 (Sorum et al., 2022).


Immune dysfunction


Treatment for coccidioides is often required for many months to years in human patients (Galgiani et al., 2016), as reported in the donkey by Sorum et al. (2022). After treatment discontinuation in human patients, approximately one-third of apparently successfully controlled cases relapse. Therefore, some patients may require lifelong therapy, though these patients often have deficiencies in cellular immunity (Galgiani & Thompson, 2016). Complications from coccidioidal infection are not uncommon when there is coexistence of major immunosuppressive conditions such as in AIDS in HIV- infected persons, and those being treated with antitumour necrosis factor therapy for rheumatologic conditions or immunosuppressive therapy to prevent rejection of organ transplants (Galgiani & Thompson, 2016). Human patients with diabetes have an increased risk of pulmonary complications (Santelli et al., 2006). Pregnant women who contract Valley Fever during pregnancy are at particular risk of serious infection, especially in the third trimester or immediately post- partum (Galgiani & Thompson, 2016). Although there was no investigation of immunodeficiency in


the donkey, serum protein electrophoresis to measure relative IgM and IgG antibody concentrations; immunophenotyping of peripheral blood lymphocytes using flow cytometry to determine B cell, CD4+ and CD8+ T cell lymphocyte proportions and cell-mediated immune responses such as opsonisation capacity, phagocytosis and oxidative burst functions of peripheral neutrophils and monocytes could be recommended (Costa, 2020).


Treatment


In human patients, many infections are resolving by the time of diagnosis and antifungal therapy is not required. The recommendation is to provide patient education, close observation and physical therapy for patients with mild or non-debilitating symptoms (Galgiani et al., 2016). Antifungal therapy with oral fluconazole is only recommended for human patients with significant debilitating illness, those with extensive pulmonary involvement, concurrent diabetes, the elderly or those frail with comorbidities. Surgical resection is occasionally required in people with thoracic cavity lesions that are persistently symptomatic despite antifungal treatment for more than 2 years and if symptoms recur on cessation of antifungal therapy (Galgiani et al., 2016). Antifungal agents successful in the treatment of infected


human patients, dogs, horses and other mammalian species include oral administration the azole antifungals itraconazole and fluconazole (Galgiani & Thompson, 2016; Higgins et al., 2005a; Stewart & Cuming, 2015). Azole antifungals inhibit cytochrome P450-dependent 14a–sterol demethylase, which is required for the formation of ergosterol, which is a component of fungal cell membranes. Oral fluconazole at 5 mg/kg bwt q. 24 h after a loading dose of 14 mg/kg bwt,


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