SEROLOGIC STUDIES IN COCCIDIOIDOMYCOSIS

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SEROLOGIC STUDIESIN COCCIDIOIDOMYCOSIS

• Demosthenes Pappagianis, M.D., Ph.D
• School of Medicine
• University of California, Davis, CA

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Life Cycle of Coccidioides
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Diagnostic Tests for Fungal Infection

• Direct Demonstration
• Microscopic body fluid, exudates (pus), sputum,
  biopsy-tissue
• Molecular PCR to detect DNA
• Culture
• Morphologic identification
• Molecular identification
• DNA probe RNA hybridized to compatible DNA
• Polymerase chain reaction to detect DNA
• Indirect
• Serologic
• Detection of antigen of fungus
• Detection of antibody response to fungus
• Biochemical
• Detection of fungal wall beta glucan or
  galactomannan in body fluids
• Detection of metabolite, e.g. D-arabinitol by
  Candida albicans

D.P. 2007
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DNA Probe
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un
control
110
Tube precipitin test
Serum Constant volume Antigen Undiluted,
110 Control No antigen
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Components and Reactions in Complement Fixation
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Examples of Complement Fixation Results
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Sequence of Immune Responses in Coccidioidomycosis
Precip tube precipitin test CF complement
fixation test
Smith, et al (1950)
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Sequence of Antibody Responses
Shaded areas for immunodiffusion with
concentrated serum, or EIA
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CF titer in Various Clinical Forms
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The declining complement fixation titer is
favorable, but in an immunocompromised patient a
decrease in titer may be the result of a
diminished humoral responsiveness.
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Qualitative immunodiffusion
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CF titer
TS58 Antigen 110
1128
164
132
116
18
14
12
gt12
Counterimmunoelectrophoresis (CIE)
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Quantitative immunodiffusion
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Johnson, S. et al 1996
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Johnson, S. et al 1996
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(IgM)
(IgG)
Figure 1. Reactivity of coccidioidal IgA in sera
of patients with coccidioidomycosis positive for
IgM, IgG or both.
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Basilar coccidioidal meningitis
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CSF Compartments
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Ommaya reservoir and catheter in lateral venticle
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Ventriculo-atrial shunt
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Lytic coccidioidal lesion of a vertebra
Herron et al., 1997 Spinal Disorders
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Juxtadural vertebral lesion
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Cerebrospinal Fluid Findings
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ELISA-Ab
CF/TP
ELISA-Ag
Coccidioidal antigenemia
Galgiani et al. 1991
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Additional Tests for Coccidioidal Antigen in
Humans

• Antigenuria and antigenemia using
  cross-reactions between coccidioidal antigen and
  anti-histoplasma antibody.Kuberski, Wheat et
  al., 2007
• Antigenemia using equine coccidioidal antibody.
  Miller, C.M., Johnson, S.M., Pappagianis, D.,2007