The Natural History of Coccidioidal Meningitis: VA--Armed Forces Cooperative Studies, 1955-1958

Abstract

From records on the clinical course of 699 military and veteran patients who had coccidioidomycosis before the advent of effective antifungal therapy, we identified 25 cases in which the manifestations of meningeal dissemination were described. Of 21 patients who had an identifiable initial infection, 16 developed meningeal symptoms (most frequently headache, vomiting, and nuchal rigidity) within the next 6 months. Associated pulmonary lesions were significantly more frequent in the right than in the left lung, as was also the case among 47 matched control patients who had coccidioidomycosis but not meningitis. Of 17 patients whose meningeal symptoms developed during the period studied, all died within 31 months. However, four of eight patients whose onset of symptoms preceded the study period survived for 55-146 months. Patients whose extrapulmonary dissemination involved only the meninges survived significantly longer than did those with more extensive infections. Even without therapy, the white blood cell count in cerebrospinal fluid markedly decreased during the course of the infection. The quantitative analysis provided herein offers a basis for meaningful comparisons with patients enrolled in current and future trials of therapy for coccidioidal meningitis.

Comparison of Itraconazole and Fluconazole Treatments in a Murine Model of Coccidioidal Meningitis

“…Mice were injected with 50 l of the inoculum intrathecally, as described previously (22). In untreated mice, this produces a progressive lethal infection (an outcome identical to untreated human coccidioidal meningitis [9,41]). There is late dissemination from the CNS to visceral organs.…”

“…Thus, both itraconazole and fluconazole were effective at controlling CM, but neither eliminated Coccidioides from tissues. Overall, itraconazole was more efficacious on an mg/kg basis; at high doses they were similarly effective.Meningitis is the most severe form of coccidioidomycosis in humans and is associated with frequent relapses and high mortality (8,9,11,14,23,33,35,41,42). The traditional treatment for coccidioidal meningitis (CM) had been administration of amphotericin B directly into the cerebrospinal fluid (CSF) by the lumbar or cisternal route or into the ventricles or other sites through a reservoir (9, 24, 35).…”

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

“…Coccidioidal meningitis is one of the most severe and devastating fungal diseases, with over 200 new cases occurring annually (7). 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.…”

Coccidioidomycosis

“…Untreated, meningitis is fatal within a few months, although there are rare reports of survival for 2 or more years [54]. Meningitis usually develops within 6 months of the initial infection [55]. The cerebrospinal fluid has an elevated white blood cell count and protein, with depressed glucose.…”