A murine model of coccidioidal meningitis.
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/mm(3) and 33 cfu/mL. The results of histopathologic analysis were unremarkable. By day 8, all mice were culture positive (5.0 log(10) cfu in brain tissue and 4.1 log(10) cfu in spinal cord tissue); CSF samples contained 4833 leukocytes/mm(3) 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.
Kamberi
Perparim
P
California Institute for Medical Research and Department of Medicine, Division of Infectious Diseases, Santa Clara Valley Medical Center, San Jose, California 95128, USA.
Sobel
Raymond A
RA
Clemons
Karl V
KV
Stevens
David A
DA
Pappagianis
Demosthenes
D
Williams
Paul L
PL
D000818:Animals; D000935:Antifungal Agents / Q000627:therapeutic use; D003045:Coccidioides / Q000502:physiology; D003047:Coccidioidomycosis / Q000134:cerebrospinal fluid / Q000150:complications / Q000188:drug therapy / Q000382:microbiology; D003433:Crosses, Genetic; D004195:Disease Models, Animal; D007654:Ketoconazole / Q000627:therapeutic use; D008297:Male; D016921:Meningitis, Fungal / Q000134:cerebrospinal fluid / Q000150:complications / Q000188:drug therapy / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008815:Mice, Inbred Strains; D015996:Survival Rate; D013997:Time Factors; D020293:Vasculitis, Central Nervous System / Q000150:complications
D000935:Antifungal Agents; D007654:Ketoconazole