Early Treatment With Fluconazole May Abrogate the Development of IgG Antibodies in Coccidioidomycosis
ABSTRACT We have observed a number of patients who fail to develop coccidioidal complement fixing (CF) antibody (immunoglobulin [IgG]) after the initiation of early antifungal therapy. Although this is the first description of this phenomenon in mycology, a precedent for the abrogation of the immune response has been observed in other conditions, including primary syphilis and primary Lyme disease.
We conducted a retrospective case-control study to determine any patient-specific risk factors associated with this observation. Additionally, in vitro analysis of the coccidioidal CF (IgG) antigen (Cts1) was performed after Coccidioides was grown under escalating fluconazole concentrations.
Seventeen patients persistently positive for coccidioidal IgM antibodies without developing an IgG response (cases) were compared with 64 consecutive patients who did develop coccidioidal CF (IgG) antibodies (controls). Early treatment with antifungals (within 2 weeks of symptom onset) was associated with an abrogation of IgG antibody production (P < .001). With immunodiffusion testing, control serum demonstrated a lack of IgG seroreactivity when Coccidioides posadasii grown in the presence of escalating fluconazole doses (0.5-128 μg/mL) was used as the antigen; however, control serum remained seroreactive for the presence of IgM. The coccidioidal IgG antigen (Cts1) was shown to be diminished when cultures were grown in the presence of fluconazole, lending further in vitro plausibility to our findings.
The abrogation of an IgG response in patients treated early in the course of coccidioidal infection may complicate serodiagnosis and epidemiologic studies, and further study to determine the potential clinical implications should be performed.
Article: The Future of Fungal Serology[Show abstract] [Hide abstract]
ABSTRACT: The incidence of invasive fungal infections continues to grow. Early and rapid diagnosis is essential to prevent morbidity and mortality. The number of assays available for the detection of fungal antigens in human body fluids are increasing in number and becoming part of the basic diagnostic workup for many fungal infections. Detection of specific antibody has been an important component in the diagnosis of fungal infections. Complement fixation and immunodiffusion continue to be the gold standard for antibody detection but are complex to perform, require extensive expertise, and are mostly performed in reference labs. Newer assays are being developed to reduce turn-around time, but have not been fully evaluated. A challenge for improving serologic assays is to move from crude antigens and polyclonal antibodies to purified and/or recombinant antigens and monoclonal antibodies, while retaining good sensitivity and specificity. Recent developments using lateral flow methodology have provided novel point-of-care antigen assays requiring little technical expertise. Such innovative techniques will help to keep the future of fungal serology bright.Current Fungal Infection Reports 09/2013; 7(3). DOI:10.1007/s12281-013-0146-x
Article: A Case of Coccidioidal Meningitis[Show abstract] [Hide abstract]
ABSTRACT: A 35-year-old man with known coccidioidal meningitis developed a severe headache and vomiting during routine treatment. Hydrocephalus was visible on brain imaging, and CSF study revealed pleocytosis, lowering of glucose, and increased intracranial pressure. Dexamethasone and mannitol was used for intracranial pressure control. Intrathecal amphotericin B administration and switching to itraconazole resulted in gradual improvement of symptoms. After 4 months of discontinuing amphotericin B intrathecal administration, the patient developed severe headaches with vomiting, diplopia and tandem gait. Coccidioidal meningitis aggravation was suspected based on brain MRI and CSF studies. Ventriculo-peritoneal shunt insertion was performed for intracranial pressure control and the combined therapy of intrathecal amphotericin B administration and fluconazole was maintained. This combined regimen kept the meningitis stable for 1 month.01/2012; 44(2):75. DOI:10.3947/ic.2012.44.2.75
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ABSTRACT: The serum (1→3)-β-d-glucan assay has emerged as an important diagnostic test for invasive fungal disease. The utility of this assay in coccidioidomycosis has not been previously studied. Using a cutoff value of ≥80 pg/ml, we found the sensitivity (43.9%), specificity (91.1%), positive predictive value (81.8%), and negative predictive value (64.1%) to be similar to those of the assay in diagnosing other invasive mycoses.Journal of clinical microbiology 06/2012; 50(9):3060-2. DOI:10.1128/JCM.00631-12 · 3.99 Impact Factor