View source for Coccidioides immitis

*Dimorphic fungus in patients from arid areas in SW US and Mexico, which is mostly asymptomatic but can cause pulmonary disease, and rarely disseminated disease. Also called Joaquin Valley fever.

==Background==
===Microbiology===

*Dimorphic fungus with barrel-shaped arthroconidia in the septated hyphal filamentous form
*Coccidiomycosis also caused by ''Coccidioides posadasii'' outside of California

===Epidemiology===
[[File:Coccidiomycosis_map.png|thumb|Distribution of coccidiomycosis]]

*Found in thermic soils in arid regions
*May have an association with small desert mammals, though of unclear significance
*''C. immitis'' in California, ''C. posadasii'' outside of California (southwestern US, Mexico, Central and South America)
*Incidence in US is increasing over the past few decades, including emergence in Washington state
**Unlikely to be from increased detection
**95% of cases are in California and Arizona
*Exposures include archaeological sites, desert exposures, dust storms, prisons
**It is a significant laboratory hazard
*There is a strain with a mutation that can cause aggressive invasive disease in younger adults

===Pathophysiology===

*Arthroconidia break off of the filamentous form and are inhaled (or inoculated)
*The then transform into invasive yeast form, characterized by spherules that contain hundreds of endospores
*The spherules rupture, releasing the endospores and continuing the cycle

==Clinical Manifestations==

*Variable, from asymptomatic or mild (60%), to symptomatic (40%), to disseminated and fulminant
*Incubation period of [[Usual incubation period::1 to 3 weeks]]
*Common symptoms:
**General: fever, arthralgia, myalgia, night sweats
**Pulmonary: cough, chest pain
**May be a common cause of community-acquired pneumonia in some endemic regions.
**Non-specific maculopapular rash (days to weeks after initial fever)
*May have peripheral eosinophilia
*Pulmonary infection may present as an acute pneumonia to a chronic pneumonia with fibronodular or fibrocavitary appearance
**May also have a solitary nodule or a pleural effusion
*Skin infection can present at site of inoculation, or disseminated
**Can cause verrucous granulomatous lesions
**[[Causes::Erythema nodosum]] may be seen
**[[Causes::Erythema multiforme]]
**Non-specific examenthem
*[[Causes::Osteomyelitis]] and native joint [[Causes::septic arthritis]], with the vertebral being to the most common site of infection
**May also cause arthralgias
*CNS infection with [[Causes::meningitis]], presenting as a chronic headache weeks to months after initial infection
**Onset of meningitis is usually around 5 weeks following onset of respiratory symptoms
**Typically basilar meningitis but can be other
**Can cause prostatitis
*Symptoms may take weeks to many months to resolve

===Desert rheumatism===

*[[Erythema nodosum]]
*Fevers
*Arthralgias

===Complications===

*Chronic pulmonary disease:
**Residual lung nodules (~5%)
**Lung cavity (~5%)
*Extra-pulmonary dissemination (skin, bones, joints, CNS): ≤1%

===Risk factors for disseminated disease===

*Immunosuppression, including [[HIV]]/AIDS, [[pregnancy]], [[TNF-α inhibitors]], [[corticosteroids]], and transplantation
*More common in non-Caucasian populations
*Age &gt;65 years, diabetes, underlying cardiac or respiratory disease
*High complement fixation titre &gt;1:16

==Differential Diagnosis==

*Infectious
**Bacterial: routine bacterial causes of [[pneumonia]]
**Fungal: [[Cryptococcus]] and other endemic fungi
**Mycobacterial: [[tuberculosis]]
**Viral?
*Non-infectious

== Investigations ==

* CT chest[[CiteRef::jude2014pu]]
** Acute disease: lobar and segmental consolidations (75%); multifocal consolidation; nodules; rarely, miliary disease or confluent nodules with cavitation; may have adenopathy or pleural effusions; may have [[ARDS]]
** Chronic changes: residual nodules, chronic cavities, persistent pneumonia with or without adenopathy, pleural effusion, and regressive changes

==Diagnosis==

*Direct microscopy: typical spherules
*Culture: fluffy white colonies on routine bacterial or fungal cultures, often within a few days (grows quickly)
*Serology
**EIA for IgM and IgG (used in Ontario)
***Sensitivity and specificity of 11-57% and 70-100% for IgM, and 53-69% and 95-99% for IgG, varies by test and laboratory[[CiteRef::humphries2023re]]
**Immunodiffusion (ID) for IgM and IgG, plus complement fixation (CF) for IgG
***ID IgM on CSF for coccioidal meningitis
**Beta glucan in blood or CSF, but isn't specific
**Coccidioidal antigen (urine and serum), only useful in disseminated disease
*For CNS involvement:
**Check opening pressure, send for fungal culture (25% sensitive), CSF serology (ID or CF, 30-60% sensitive), CSF coccidioidal antigen
**Glucose normal or low, protein high or normal, predominately lymphocytosis, may have eosinophils
**Rule out Cryptococcus and TB

==Management==

*Many do not need treatment, as infection is asymptomatic or self-limited
**Not indicated for asymptomatic pulmonary nodules or cavities in immunocompetent people
*Indications
**Significant, debilitating illness requiring hospitalization
**Extensive pulmonary involvement with diabetes, older age, or other comorbidities
**Chronic cavitary coccidioidal pneumonia
**Ruptured coccidioidal cavities
**Extrapulmonary soft tissue infections and bone and joint infections
**Meningitis
**High-risk populations: HIV with CD4<250, hematopoietic stem cell transplant, solid organ transplant
**For immunocompetent, ambulatory patients with acute pulmonary infection, one of
***Weight loss >10%
***Night sweats for 3 weeks
***Infiltrates on more than half of one lung or portions of both
***Prominent or persistent hilar adenopathy
***Anticoccidioidal complement fixation antibody titres over 1:16
***Inability to work
***Symptoms lasting >2 months
*Treatment regimens
**[[Is treated by::Fluconazole]] 400-800 mg/day
**May use [[Is treated by::itraconazole]], [[Is treated by::voriconazole]], [[Is treated by::posaconazole]], or [[Is treated by::isavuconazole]]
**May use [[Is treated by::amphotericin B]] if life-threatening infections, pregnancy, or refractory to azole therapy
**Slight preference for itra for bone &amp; joint infections
*Duration
**Acute pulmonary disease: 3 to 6 months, or longer
**Chronic pulmonary infection: 8 to 12 months, or longer
**Bone and joint disease: [[amphotericin B]] induction x 3 months followed by 3+ years of azoles
*Meningitis
**High-dose fluconazole until clinical improvement, then lifelong [[fluconazole]] 400 mg daily
**Daily therapeutic LP titrated to opening pressure (like cryptococcal meningitis)

===Laboratory Exposure===

*Evacuate lab, seal lab, call Biosafety Officer on call
*Assess risk to each individual exposed
**Lower early in culture when it's yeast-like, higher later when it's a well-grown filamentous fungus (usually by 7 to 10 days)
**Lifting the lid once likely less than breaking the container
**However, note that in lab exposures, the number of arthroconidia inhaled is often much higher than a natural inoculum, and attack rates are higher than natural exposure
*For exposed personnel
**Get baseline serology (if prior exposure, they're at lower risk)
**Treat with therapeutic-dose itra or fluc 400 mg daily for 6 weeks, as prophylaxis
***If pregnant, would have to consider prophylactic amphotericin; use of fluconazole may depend on trimester
**Repeat serology after prophylaxis; if seroconversion, then consider treating for another few months
**If they become symptomatic during or after prophylaxis, either with fever or respiratory symptoms, they should be further evaluated
***Serology can lag by 3 to 12 weeks following symptoms
**Continue to follow for up to 1 year

{{DISPLAYTITLE:''Coccidioides immitis''}}
[[Category:Dimorphic fungi]]