A murine model of Coccidioidal meningitis

Perparim Kamberi, Raymond A. Sobel, Karl V. Clemons, David A. Stevens, Demosthenes Pappagianis, Paul L. Williams

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Coccidioidal meningitis is lethal in humans. A reproducible murine model was established by lumbar intrathecal injection of Coccidioides immitis arthroconidia. Cerebrospinal fluid (CSF) samples were obtained by cisternal puncture. Lethal infection developed in all mice given 10-60 colony-forming units (cfu). Lethargy, ataxia, or paralysis preceded death. Temporal studies after challenge with 27 cfu revealed positive brain (4/5 mice) and spinal cord (2/5 mice) cultures on day 3; CSF samples contained 688 leukocytes/mm3 and 33 cfu/mL. The results of histopathologic analysis were unremarkable. By day 8, all mice were culture positive (5.0 log10 cfu in brain tissue and 4.1 log10 cfu in spinal cord tissue); CSF samples contained 4833 leukocytes/mm3 and 3425 cfu/mL. Histopathologic examinations showed acute meningitis of the brain and spinal cord, some parenchymal invasion and abscesses, and meningeal arteritis. Groups of mice given ketoconazole had prolonged survival and suppressed lung disease; histopathologic examination demonstrated granulomatous meningitis, possibly a more chronic form. With the development of these models, studies of pathogenesis, host response, and therapy are possible.

Original languageEnglish (US)
Pages (from-to)453-460
Number of pages8
JournalJournal of Infectious Diseases
Volume187
Issue number3
DOIs
StatePublished - Feb 1 2003

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Immunology

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    Kamberi, P., Sobel, R. A., Clemons, K. V., Stevens, D. A., Pappagianis, D., & Williams, P. L. (2003). A murine model of Coccidioidal meningitis. Journal of Infectious Diseases, 187(3), 453-460. https://doi.org/10.1086/367961