Coccidioides immitis: Difference between revisions

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Coccidioides immitis
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* 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.
 +
*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 =
  
  +
===Microbiology===
   
−
* Dimorphic fungus with barrel-shaped arthroconidia in the septated hyphal filamentous form
 +
*Dimorphic fungus with barrel-shaped arthroconidia in the septated hyphal filamentous form
−
* Coccidiomycosis also caused by ''Coccidioides posadasii'' outside of California
 +
*Coccidiomycosis also caused by ''Coccidioides posadasii'' outside of California
   
−
= Epidemiology =
 +
===Epidemiology===
  +
[[File:Coccidiomycosis_map.png|thumb|Distribution of coccidiomycosis]]
   
−
* Found in thermic soils in arid regions
 +
*Found in thermic soils in arid regions
−
* May have an association with small desert mammals, though of unclear significance
 +
*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)
 +
*''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
 +
*Incidence in US is increasing over the past few decades, including emergence in Washington state
−
** Unlikely to be from increased detection
 +
**Unlikely to be from increased detection
−
** 95% of cases are in California and Arizona
 +
**95% of cases are in California and Arizona
−
* Exposures include archaeological sites, desert exposures, dust storms, prisons
 +
*Exposures include archaeological sites, desert exposures, dust storms, prisons
−
** It is a significant laboratory hazard
 +
**It is a significant laboratory hazard
−
* There is a strain with a mutation that can cause aggressive invasive disease in younger adults
 +
*There is a strain with a mutation that can cause aggressive invasive disease in younger adults
   
−
= Pathophysiology =
 +
===Pathophysiology===
   
−
* Arthroconidia break off of the filamentous form and are inhaled (or inoculated)
 +
*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 then transform into invasive yeast form, characterized by spherules that contain hundreds of endospores
−
* The spherules rupture, releasing the endospores and continuing the cycle
 +
*The spherules rupture, releasing the endospores and continuing the cycle
   
−
= Clinical Presentation =
 +
==Clinical Manifestations==
   
−
* Variable, from asymptomatic or mild (60%), to symptomatic (40%), to disseminated and fulminant
 +
*Variable, from asymptomatic or mild (60%), to symptomatic (40%), to disseminated and fulminant
−
* Incubation period 1-3 weeks
 +
*Incubation period of [[Usual incubation period::1 to 3 weeks]]
−
* Common symptoms:
 +
*Common symptoms:
−
** General: fever, arthralgia, myalgia, night sweats
 +
**General: fever, arthralgia, myalgia, night sweats
−
** Pulmonary: cough, chest pain
 +
**Pulmonary: cough, chest pain
−
** May be a common cause of community-acquired pneumonia in some endemic regions.
 +
**May be a common cause of community-acquired pneumonia in some endemic regions.
−
** Non-specific maculopapular rash (days to weeks after initial fever)
 +
**Non-specific maculopapular rash (days to weeks after initial fever)
−
* May have peripheral eosinophilia
 +
*May have peripheral eosinophilia
−
* Pulmonary infection may present as an acute pneumonia to a chronic pneumonia with fibronodular or fibrocavitary appearance
 +
*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
 +
**May also have a solitary nodule or a pleural effusion
−
* Skin infection can present at site of inoculation, or disseminated
 +
*Skin infection can present at site of inoculation, or disseminated
−
** Can cause verrucous granulomatous lesions
 +
**Can cause verrucous granulomatous lesions
−
** Erythema nodosum may be seen
 +
**[[Causes::Erythema nodosum]] may be seen
−
** Erythema multiforme
 +
**[[Causes::Erythema multiforme]]
−
** Non-specific rash
 +
**Non-specific examenthem
−
* Osteomyelitis and native joint infections, with the vertebral being to the most common site of infection
 +
*[[Causes::Osteomyelitis]] and native joint [[Causes::septic arthritis]], with the vertebral being to the most common site of infection
−
** May also cause arthralgias
 +
**May also cause arthralgias
−
* CNS infection with meningitis, presenting as a chronic headache weeks to months after initial infection
 +
*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
 +
**Onset of meningitis is usually around 5 weeks following onset of respiratory symptoms
−
** Typically basilar meningitis but can be other
 +
**Typically basilar meningitis but can be other
−
** Can cause prostatitis
 +
**Can cause prostatitis
−
* Symptoms may take weeks to many months to resolve
 +
*Symptoms may take weeks to many months to resolve
   
−
== Desert rheumatism ==
 +
===Desert rheumatism===
   
−
* Erythema nodosum
 +
*[[Erythema nodosum]]
−
* Fevers
 +
*Fevers
−
* Arthralgias
 +
*Arthralgias
   
−
== Complications ==
 +
===Complications===
   
−
* Chronic pulmonary disease:
 +
*Chronic pulmonary disease:
−
** Residual lung nodules (~5%)
 +
**Residual lung nodules (~5%)
−
** Lung cavity (~5%)
 +
**Lung cavity (~5%)
−
* Extra-pulmonary dissemination (skin, bones, joints, CNS): ≤1%
 +
*Extra-pulmonary dissemination (skin, bones, joints, CNS): ≤1%
   
−
== Risk factors for disseminated disease ==
 +
===Risk factors for disseminated disease===
   
−
* Immunosuppression, including HIV/AIDS, pregnancy, TNF inhibitors, corticosteroids, and transplantation
 +
*Immunosuppression, including [[HIV]]/AIDS, [[pregnancy]], [[TNF-α inhibitors]], [[corticosteroids]], and transplantation
−
* More common in non-Caucasian populations
 +
*More common in non-Caucasian populations
−
* Age >65 years, diabetes, underlying cardiac or respiratory disease
 +
*Age >65 years, diabetes, underlying cardiac or respiratory disease
−
* High complement fixation titre >1:16
 +
*High complement fixation titre >1:16
   
−
= Differential Diagnosis =
 +
==Differential Diagnosis==
   
−
* Infectious
 +
*Infectious
−
** Bacterial: routine bacterial infections
 +
**Bacterial: routine bacterial causes of [[pneumonia]]
−
** Fungal: cryptococcosis, other endemic fungi
 +
**Fungal: [[Cryptococcus]] and other endemic fungi
−
** Mycobacterial: TB
 +
**Mycobacterial: [[tuberculosis]]
−
** Viral?
 +
**Viral?
−
* Non-infectious
 +
*Non-infectious
   
  +
== Investigations ==
−
= Diagnosis =
  
   
  +
* CT chest<ref>Jude CM, Nayak NB, Patel MK, Deshmukh M, Batra P. Pulmonary coccidioidomycosis: pictorial review of chest radiographic and CT findings. ''Radiographics''. 2014 Jul-Aug;34(4):912-25. doi: [https://doi.org/10.1148/rg.344130134 10.1148/rg.344130134]. PMID: [https://pubmed.ncbi.nlm.nih.gov/25019431/ 25019431].</ref>
−
* Direct microscopy: typical spherules
  
  +
** 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]]
−
* Culture: fluffy white colonies on routine bacterial or fungal cultures, often within a few days (grows quickly)
  
  +
** Chronic changes: residual nodules, chronic cavities, persistent pneumonia with or without adenopathy, pleural effusion, and regressive changes
−
* Serology
  
−
** Immunodiffusion (ID) for IgM and IgG
  
−
*** IgM on CSF for coccioidal meningitis
  
−
** Complement fixation for IgG
  
−
** 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
  
   
  +
==Diagnosis==
−
= Management =
  
   
  +
*Direct microscopy: typical spherules
−
* Many do not need treatment, as infection is asymptomatic or self-limited
  
  +
*Culture: fluffy white colonies on routine bacterial or fungal cultures, often within a few days (grows quickly)
−
* Indications
  
  +
*Serology
−
** High-risk groups: immunocompromised/suppressed, diabetes, elderly, comorbidities
  
  +
**Immunodiffusion (ID) for IgM and IgG
−
** High-risk infection: extensive pulmonary disease, severe symptoms, persistent disease (especially lasting more than 2 months), complement fixation &gt;1:16
  
  +
***IgM on CSF for coccioidal meningitis
−
** Extrapulmonary disease
  
  +
**Complement fixation for IgG
−
* Treatment regimens
  
  +
**Beta glucan in blood or CSF, but isn't specific
−
** Fluconazole 400-800 mg/day
  
  +
**Coccidioidal antigen (urine and serum), only useful in disseminated disease
−
** May use itraconazole, voriconazole, posaconazole, or isavuconazole
  
  +
*For CNS involvement:
−
** May use amphotericin if life-threatening infections, pregnancy, or refractory to azole therapy
  
  +
**Check opening pressure, send for fungal culture (25% sensitive), CSF serology (ID or CF, 30-60% sensitive), CSF coccidioidal antigen
−
** Slight preference for itra for bone &amp; joint infections
  
  +
**Glucose normal or low, protein high or normal, predominately lymphocytosis, may have eosinophils
−
* Duration
  
  +
**Rule out Cryptococcus and TB
−
** Acute pulmonary disease: 3 to 6 months, or longer
  
−
** Chronic pulmonary infection: 8 to 12 months, or longer
  
−
** Bone and joint disease: ampho 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 crypto)
  
   
  +
==Management==
−
== Laboratory Exposure ==
  
   
  +
*Many do not need treatment, as infection is asymptomatic or self-limited
−
* Evacuate lab, seal lab, call Biosafety Officer on call
  
  +
**Not indicated for asymptomatic pulmonary nodules or cavities in immunocompetent people
−
* Assess risk to each individual exposed
  
  +
*Indications
−
** 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)
  
  +
**Significant, debilitating illness requiring hospitalization
−
** Lifting the lid once likely less than breaking the container
  
  +
**Extensive pulmonary involvement with diabetes, older age, or other comorbidities
−
** 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
  
  +
**Chronic cavitary coccidioidal pneumonia
−
* For exposed personnel
  
  +
**Ruptured coccidioidal cavities
−
** Get baseline serology (if prior exposure, they're at lower risk)
  
  +
**Extrapulmonary soft tissue infections and bone and joint infections
−
** Treat with therapeutic-dose itra or fluc 400 mg daily for 6 weeks, as prophylaxis
  
  +
**Meningitis
−
*** If pregnant, would have to consider prophylactic amphotericin; use of fluconazole may depend on trimester
  
  +
**High-risk populations: HIV with CD4<250, hematopoietic stem cell transplant, solid organ transplant
−
** Repeat serology after prophylaxis; if seroconversion, then consider treating for another few months
  
  +
**For immunocompetent, ambulatory patients with acute pulmonary infection, one of
−
** If they become symptomatic during or after prophylaxis, either with fever or respiratory symptoms, they should be further evaluated
  
  +
***Weight loss >10%
−
*** Serology can lag by 3 to 12 weeks following symptoms
  
  +
***Night sweats for 3 weeks
−
** Continue to follow for up to 1 year
  
  +
***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''}}
  
{{DISPLAYTITLE:''Coccidioides immitis''}}

Latest revision as of 13:13, 14 December 2023

  • 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

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 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
  • Osteomyelitis and native joint septic arthritis, with the vertebral being to the most common site of infection
    • May also cause arthralgias
  • CNS infection with 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

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 >65 years, diabetes, underlying cardiac or respiratory disease
  • High complement fixation titre >1:16

Differential Diagnosis

Investigations

  • CT chest[1]
    • 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
    • Immunodiffusion (ID) for IgM and IgG
      • IgM on CSF for coccioidal meningitis
    • Complement fixation for IgG
    • 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
  • 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
  1. ↑ Jude CM, Nayak NB, Patel MK, Deshmukh M, Batra P. Pulmonary coccidioidomycosis: pictorial review of chest radiographic and CT findings. Radiographics. 2014 Jul-Aug;34(4):912-25. doi: 10.1148/rg.344130134. PMID: 25019431.
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