Coccidioidal Meningitis

Background- Dimorphic fungus found in the soil, two main species:

- C. imitis in SW US esp California- C. posadasii in northern Mexico and other parts of Central and South America

- Cocci meningitis first described by Ophuls in 1905- is increasingly diagnosed in endemic areas btw 1997 & 2006 incidence quadrupled to 91 per 100,000 with

60% of cases coming from Arizona- 60% of infections are asymptomatic, the remainder have mainly pulmonary symptoms- 1-5% of symptomatic pts have extra pulmonary infxn wks to months after the initial infection

- skin & soft tissues, bones/joints, CNS (meningitis in 0.15% to 0.75% of cases)

- those at higher risk for severe/disseminated infections include:- persons w/deficient cellular immunity e.g. HIV +, those on chemo/steroids- Mexican, Native American, Filipinos and Africans more likely than Caucasians- Males more likely than females- pregnancy- comorbid medical illness like diabetes- hematological malignancies or other cancers

Clinical manifestations- symptoms are similar to bacterial meningitis: persistent headache, nausea, photophobia, neck pain &

stiffness, back pain, confusion, decline in cognition or memory, emotional lability, hearing/visual changes- Focal neurologic deficits/seizures in pts with CM may result from vasculitis or mass lesions; CNS abscesses

may be multiple or single and can be found throughout the brain- typically located in basilar meninges, but may be diffuse and uncommonly involves lateral cerebral ventricles- suppurative & granulomatous infection of leptomeninges > thick membrane of inflammation and fibrous

tissue that obliterates the subarachnoid space in some areas causing obstruction to flow of CSF > ventricular dilation and hydrocephalus

- hydrocephalus complicates 20-50% of cases and increases risk of mortality 12 fold- hydrocephalus should be suspected if CSF pressure is consistently elevated, pt doesnt respond to tx,

signs of increased ICP (headache, n/v, personality changes)- decompression with shunt improves pressure & symptoms, but shunts are associated w/growth of the

mycelial form of the fungus > increase risk of device obstruction

Diagnosis- analysis of CSF is the only means to establish diagnosis of cocci meningitis: need 1/3 of the following a +

CSF culture (isolation occurs in ~15% of patients), hisopath identification of endosporulating spherules or + CSF serology (complement fixing abs; O/N cold incubation is 95% sensitive, sometimes serial CSF exams needed; ELISA less reliable)

-CSF will typically show elevated nucleated cell count & total protein

- CSF eosinophilic pleocytosis identified in 70% of pts in one study, but other authors report this finding to be uncommon

- glucose generally low- Neuroimaging abnormalities seen in up to 75% of patients, those w/abnormalities have higher mortality rate

(32%) vs 8% for those without- most commonly see diffuse meningeal enhancement, but focal enhancement of basal cisterns, Sylvian

fissures, craniocervical junction or pericallosal regions can be seen- may also see hydrocephalus, acute deep cerebral infarcts/edema, massess/abscesses

Treatment: If untreated, meningitis is lethal for 95 percent of patients within two years- Polyenes (Ampho B .01 to 1.5 mg and newer lipid formulations) used for more serious forms of disease,

ineffective for meningitis if given IV has to be given intrathecal- intrathecal AMB can cause meningeal irritation > fever, headache, pain in abd or back- reservoirs for IT insulation of AMB can be placed- lipid formulations have cured CM animals when given IV, no human studies- relapse rate ~30%

- Azoles: Voriconazole used more often in life threatening mycoses- in one study 79% of pets responded to 400 mg oral fluconazole- itraconazole 200 mg TID or BID, doesnt penetrate CSF well but has been shown to be able to treat

CM, likely due to penetration into inflamed meninges- 400 mg Posaconazole BID highly active against Cocci in vitro, used successfully in one study to treat

62% of patients w/refractory infection or those intolerant of other drugs- high risk of relapse after azole discontinuation studies ~78% so need to continue treatment for life

- focal neurologic complications may emerge during tx, esp within the first 2 years, it is useful to perform MRI of both the head and spinal cord at baseline and in follow-up

References:1) Blair JE. Coccidioidal Meningitis: update on Epidemiology, Clinical Features, Diagnosis, and Management. Current

Infectious Disease Reports. 2009. 11:289-295. 2) Hector RF and Laniado-Laborin R. Cocidiomycosis-A Fungal Disease of the Americas. PLoS Medicine. 2005.3) Galgiani JN, Ampel NM, Catanzaro A, Johnson RH, Stevens DA, et al. (2000) Practice guidelines for the treatment of

coccidioidomycosis. Clin Infect Dis 30: 658661.4) Goldstein EJ, Johnson RH, and Einstein HE. Clin Infect Dis. 2006 42 (1):103-107.5) Drake KW and Rodney AD. Coccidiodal meningitis and brain abscesses: Analysis of 71 cases at a referral center.

Neurology. 2009. 73(21):1780-6.

T1 weighted image showing arachnoiditis-thickened

compression of dura matter and spinal cord at C4

secondary to cocci T1 weighted image showing disease

involving basilar cisterns

T1 weighted image showing enhancement of the basilar

leptomeninges, communicating hydrocephalus w/enlargement of

the temporal horns

T1 weighted image showing diffuse thickening &

enhancement of the basilar meninges w/multiple foci of

infarction