Comparative Study of Newer and Established Methods of Diagnosing Coccidioidal Meningitis.

David A Stevens,Meredith Mcguire,Demosthenes Pappagianis,Marife Martinez,Gabriele Sass,Hannah Kutsche,Brian Doherty

doi:10.3390/jof6030125

Abstract

Meningitis is the most devastating form of coccidioidomycosis. A convenient, rapid diagnostic method could result in early treatment and avoid many meningitis complications. We studied cerebrospinal fluid (CSF) samples in patients with documented coccidioidal meningitis, and controls, with complement fixation (CF), immunodiffusion (ID) (the “classical” assays), lateral flow assays (LFA; one-strip and two-strip), and two enzyme immunoassays (EIA). The two-strip LFA and EIAs not only enabled separate testing for IgG and IgM antibodies separately, but also could aggregate results for each method. CF with ID or the aggregate use of IgG and IgM tests were considered optimal test uses. LFAs and EIAs were evaluated at 1:21 and 1:441 dilutions of specimens. All assays were compared to true patient status. With 49 patient specimens and 40 controls, this is the largest comparative study of CSF coccidioidal diagnostics. Sensitivity of these tests ranged from 71–95% and specificity 90–100%. IgM assays were less sensitive. Assays at 1:441 were similarly specific but less sensitive, suggesting that serial dilutions of samples could result in assays yielding titers. Agreement of positive results on cases was 87–100%. When kits are available, hospital laboratories in endemic areas can perform testing. LFA assays do not require a laboratory, are simple to use, and give rapid results, potentially even at the bedside.

Highlights

Of all the complications of disseminated coccidioidomycosis, the most lethal is meningitis; it is estimated that there are 200–500 new cases of this complication per year [1]
We studied the utility of the lateral flow assays (LFA) and enzyme immunoassays (EIA) assays with cerebrospinal fluid (CSF) specimens at two levels of patient dilution
At a 1:21 dilution the one-strip LFA had a sensitivity of 95% and a specificity of 100%, a positive predictive value (PPV) of 100% and a negative predictive value (NPV) of 86% (Table 1)

Summary

Introduction

Of all the complications of disseminated coccidioidomycosis, the most lethal is meningitis; it is estimated that there are 200–500 new cases of this complication per year [1]. Treatment with oral antifungals requires lifetime administration to suppress recurrences [2], and in many cases intrathecal (and neurotoxic) therapy is required to stop progression [3]. Because of the many complications, which include hydrocephalus, vasculitis, cerebral or spinal cord infarction, arachnoiditis, cranial nerve palsy, syringomyelia, transverse myelitis, cord compression, paralyses, parenchymal abscesses, and seizures, we deem it essential to begin treatment as early as possible, before the pathologic processes have advanced or become irreversible. Culture of cerebrospinal fluid (CSF) for Coccidioides, even in active and untreated cases, is positive in a minority of specimens, presumably relating to the focalization of disease to the meninges themselves.

Methods

Results

Conclusion