Vasculitic and Encephalitic Complications Associated with Coccidioides immitis Infection of the Central Nervous System in Humans: Report of 10 Cases and Review

Antimicrob Agents Chemother

Clemons

et al. 2000

Neither drug affected CSF glucose levels. Both compounds were effective at reducing neurological and systemic signs and extending survival (P < 0.014). FCZ was more effective at reducing head and body shakes, posture changes, and incontinence; ITZ was more effective at reducing continuous fever. Mean levels of FCZ and ITZ in the serum and CSF were determined by bioassay; at 17 to 26 h postdosing, levels were 28.1 to 40.0 and 22.4 to 29.9 g/ml, respectively, for FCZ and 0.77 to 2.51 and 0 g/ml, respectively, for ITZ. The sera of most animals developed antibody to C. immitis, but azole treatment attenuated antibody development in CSF and its titer. In conclusion, both FCZ and ITZ were efficacious, but neither was curative in a rabbit model of coccidioidal meningitis.Coccidioidomycosis is caused by the fungus Coccidioides immitis. It usually enters the body by inhalation of arthroconidia.

Section: Discussionmentioning

confidence: 89%

“…If left untreated, 90% of the patients with this disease die within 1 year and 100% die within 2 years (6,24). Complications of coccidioidal meningitis include vasculitis and stroke (25) and hydrocephalus.…”

mentioning

confidence: 99%

Comparison of Fluconazole and Itraconazole in a Rabbit Model of Coccidioidal Meningitis

Sorensen

Antimicrob Agents Chemother

Clemons

et al. 2000

“…This therapy is usually considered lifelong, and a cure is unusual (2). Patients receiving azole therapy are still at risk for other complications associated with coccidioidal meningitis, such as stroke, vasculitis, hydrocephalus, and encephalitis (17).…”

mentioning

confidence: 99%

Comparative Efficacies of Terbinafine and Fluconazole in Treatment of Experimental Coccidioidal Meningitis in a Rabbit Model

Sorensen

Antimicrob Agents Chemother

Clemons

et al. 2000

A rabbit model of coccidioidal meningitis was used to compare the therapeutic efficacies of terbinafine (TBF) and fluconazole (FCZ). Hydrocortisone acetate-treated New Zealand White male rabbits were infected intracisternally with either 2.2 ؋ 10 4 or 6.4 ؋ 10 4 Coccidioides immitis arthroconidia. Oral treatment with polyethylene glycol 200 (PEG) twice daily (n ‫؍‬ 8), TBF twice daily (n ‫؍‬ 9; 200 mg/kg of body weight/day), or FCZ once daily (n ‫؍‬ 8; 80 mg/kg/day) began on day 5 and continued for 21 days. Mean survival times were 20, 24, and 32 days for rabbits treated with PEG, TBF, and FCZ, respectively. All of the FCZ-treated animals (100%; P ‫؍‬ 0.003), 56% of the TBF-treated animals (P ‫؍‬ 0.4), and 25% of the PEG-treated animals survived the length of the study. Both FCZ and TBF were effective at reducing the incidence of paresis. Only FCZ was effective at reducing most neurological and systemic signs. FCZ treatments resulted in lower cerebrospinal fluid (CSF) protein concentrations and leukocyte counts and faster clearing of CSF fungal cultures compared with those for PEG-treated controls, but TBF treatments had no significant effect on these parameters. Neither drug affected CSF glucose levels. Mean serum TBF levels by bioassay were within the range of 3.5 to 6.2 g/ml at 1, 2, and 4 h postdosing and 0.35 to 7.0 g/ml at 14 h postdosing. No TBF was detected in CSF. Mean FCZ levels (24 to 25.5 h postdosing) by bioassay were 16.4 to 19.2 and 13.5 to 19.2 g/ml in serum and CSF, respectively. The reduction in the numbers of CFU in the spinal cord and brain was over 100-fold (P ‫؍‬ 0.0005) in FCZ-treated animals and 2-fold (P < 0.2) in TBF-treated animals compared with those in PEG-treated animals. Histopathologic severity (semiquantitative scoring system) was significantly attenuated by FCZ treatment (P ‫؍‬ 0.05) and was slightly attenuated by TBF treatment compared with that for the controls. In conclusion, TBF appeared to have a slight effect on survival, histology, and reduction of the numbers of CFU in tissue; however, these effects were not significant. FCZ was effective at controlling coccidioidal meningitis.

“…Infarcts in the central nervous system (CNS) parenchyma are common complications of coccidioidal meningitis in humans [1][2][3] and in animal models [4][5][6] and can result in significant morbidity and mortality. The underlying immunological mechanisms responsible are poorly understood but molecules known to be associated with immune response in systemic mycoses, especially those associated with Th-1 responses, are probably involved [1,7].…”

Section: Introductionmentioning

confidence: 99%

Temporal expression of inflammatory mediators in brain basilar artery vasculitis and cerebrospinal fluid of rabbits with coccidioidal meningitis

Zucker

Kamberi

Clinical and Experimental Immunology

et al. 2006

SummaryStrokes due to transmural vasculitis associated with coccidioidal meningitis result in significant morbidity and mortality. The immunological and inflammatory processes responsible are poorly understood. To determine the inflammatory mediators, i.e. cytokines, chemokines, iNOS, matrix metalloproteinase-9 (MMP-9), that possibly contribute to vasculitis, temporal mRNA expression in brain basilar artery samples and MMP-9 protein in the CSF of male NZW rabbits infected intracisternally with 6·5 × × × × 10 4 arthroconidia of Coccidioides immitis were assessed. Five infected and 3 sham-injected rabbits at each time point were euthanized 4, 9, 14 and 20 days post infection. All infected rabbits had neurological abnormalities and severe vasculitis in the basilar arteries on days 9-20. In basilar arteries of infected animals versus controls, mRNAs encoding for IL-6, iNOS, IFN-γ γ γ γ , IL-2, MCP-1, IL-1β β β β , IL-10, TNF-α α α α , CCR-1, MMP-9, TGF-β β β β , as well as MMP-9 protein in CSF, were found to be significantly up-regulated. Thus, this study identified inflammatory mediators associated with CNS vasculitis and meningitis due to C. immitis infection. Assessment of the individual contribution of each mediator to vasculitis may offer novel approaches to the treatment of coccidioidal CNS infection. This study also provides unique methodology for immunology studies in a rabbit model.