Yeast-Associated Infections

Yeasts cause a spectrum of diseases that range from colonization to uniformly fatal invasive disease. Invasive fungal disease may occur in immunocompromised patients, patients on immunomodulatory therapy or with indwelling devices, and critically ill patients. The species most likely to cause disease include cryptococcus neoformans and candida spp. Manifestations of infections may occur in one or more body sites, and often present with symptoms related to the site of involvement. For more information on fungal diseases, visit the CDC’s fungal diseases site.

Diagnosis

Indications for Testing

At-risk patients with suspected yeast-associated disease

Laboratory Testing

Respiratory – Acute Primary Infection
Histoplasma
  • Sputum fungal stain
  • Histoplasma EIA serum and/or urine
  • Tissue culture
Cryptococcus
  • Fungal stain
  • Serum Cryptococcus antigen
  • Culture

Candida

  • Tissue biopsy specimen showing invasion
  • Tissue culture

Coccidioides

  • Sputum fungal stain
  • Tissue culture
  • Serum ID
Blastomyces
  • Sputum fungal stain
  • Serum ID, CF, EIA
  • Tissue culture
  • Antigen (serum, urine) as secondary test
Trichosporon or Rhodotorula

N/A

CF, complement fixation; EIA, enzyme immunoassay; ID, immunodiffusion
Respiratory – Chronic Pulmonary Disease
Histoplasma
  • EIA serum or urine
  • Tissue culture
  • Antibody detection
Cryptococcus

N/A

Candida

N/A

Coccidioides

N/A

Blastomyces

Serum CF, ID, EIA

Trichosporon or Rhodotorula

N/A

CF, complement fixation; EIA, enzyme immunoassay; ID, immunodiffusion
Central Nervous System
Histoplasma
  • CSF stain and culture
  • Serum Histoplasma antigen
Cryptococcus
  • Serum Cryptococcus antigen
  • CSF Cryptococcus antigen
  • Culture

Candida

  • Culture
  • Fungal stain
  • (1-3) beta-D-glucan

Coccidioides

  • CSF stain and culture
  • CF, ID, and ELISA antibodies
Blastomyces
  • CSF stain and culture
  • CF and ID antibodies, EIA
Trichosporon or Rhodotorula

N/A

CF, complement fixation; CSF, cerebrospinal fluid; EIA, enzyme immunoassay; ELISA, enzyme-linked immunosorbent assay; ID, immunodiffusion
Ophthalmologic
Histoplasma
  • Culture
  • Serum Histoplasma antigen and antibody
Cryptococcus
  • Culture
  • Serum Cryptococcus antigen

Candida

  • Culture (vitreous fluid)
  • Blood culture
  • (1-3) beta-D-glucan

Coccidioides

N/A

Blastomyces

N/A

Trichosporon or Rhodotorula

N/A

Otorhinolaryngologic
Histoplasma

N/A

Cryptococcus
  • Fungal stain
  • Serum Cryptococcus antigen
  • Culture

Candida

  • Culture
  • Fungal stain

Coccidioides

N/A

Blastomyces

N/A

Trichosporon or Rhodotorula

N/A

Hepatosplenic or Gastrointestinal
Histoplasma

Serum Histoplasma antigen

Cryptococcus
  • Blood culture
  • Serum Cryptococcus antigen
  • Tissue biopsy

Candida

(1-3) beta-D-glucan

Coccidioides

N/A

Blastomyces

N/A

Trichosporon or Rhodotorula

N/A

Dermatologic
Histoplasma
  • Culture and histology of skin biopsy
  • Serum Histoplasma antigen
Cryptococcus
  • Culture of purulent material/fluid
  • Serum antigen

Candida

  • Fungal stain
  • Culture
  • Vaginal pathogens (DNA probe)

Coccidioides

  • Fungal stain of purulent material
  • CF, ID, and ELISA antibodies
Blastomyces
  • Fungal stain of purulent material
  • CF and ID antibodies, EIA
Trichosporon or Rhodotorula

Culture

CF, complement fixation; EIA, enzyme immunoassay; ELISA, enzyme-linked immunosorbent assay; ID, immunodiffusion
Bone
Histoplasma
  • Bone marrow culture
  • Serum Histoplasma antigen
Cryptococcus
  • Bone marrow culture
  • Cryptococcus antigen

Candida

  • Bone marrow culture
  • (1-3) beta-D-glucan

Coccidioides

  • Bone marrow culture
  • CF, ID, and ELISA antibodies
Blastomyces
  • Bone marrow culture
  • CF and ID antibodies, EIA
Trichosporon or Rhodotorula

N/A

CF, complement fixation; EIA, enzyme immunoassay; ELISA, enzyme-linked immunosorbent assay; ID, immunodiffusion
Genitourinary
Histoplasma
  • Urine and serum Histoplasma antigen, and CF and ID antibodies
  • Tissue biopsy (focal lesion)
  • Disseminated disease – order fungal blood culture
Cryptococcus
  • Serum Cryptococcus antigen
  • Tissue biopsy (focal lesion)

Candida

  • Fungal stain
  • Culture
  • (1-3) beta-D-glucan

Coccidioides

N/A

Blastomyces
  • Urine culture after prostatic massage
  • CF and ID antibodies, EIA
  • Tissue biopsy (focal lesion)
Trichosporon or Rhodotorula

Urine culture (Trichosporon only)

CF, complement fixation; EIA, enzyme immunoassay; ID, immunodiffusion

Background

Pulmonary Symptoms

Risk Factors for Severe Pneumonia and Disseminated Disease
Histoplasma
  • Young age
  • HIV
Cryptococcus
Candida
  • Renal failure
  • Presence of CVC/other vascular-access device
  • TPN administration
Coccidioides
  • Pregnancy
  • HIV
  • Ethnicity
    • Filipino
    • Native American
    • African American
Blastomyces
  • Pregnancy
  • Organ transplantation
  • HIV
Trichosporon or Rhodotorula

Severe illness (eg, leukemia)

CVC, central venous catheter; TPN, total parenteral nutrition
Acute Primary Pulmonary Infection
Histoplasma

Clinical picture similar to tuberculosis with fever, weight loss, and lymphadenopathy

Cryptococcus
  • Fever
  • Chest pain
  • Cough
  • Sputum
  • Weight loss
Candida
  • Fever
  • Sputum
  • Pneumonia (rare)
Coccidioides

Clinical picture similar to tuberculosis with fever, weight loss, and lymphadenopathy

Blastomyces

Clinical picture similar to influenza

Trichosporon or Rhodotorula

N/A

Chronic Pulmonary Disease
Histoplasma
  • Calcified nodes
  • Chronic cavitary disease
  • Mediastinal granuloma
  • Fibrosis
Cryptococcus

N/A

Candida N/A
Coccidioides
  • Coin lesions (coccidiomas)
  • Cavitary disease (thin walled)
  • Granulomas
Blastomyces

Chronic granulomatous disease (Gilchrist disease)

Trichosporon or Rhodotorula

N/A

Nonpulmonary Symptoms

Ophthalmologic
Histoplasma
  • Uveitis and panophthalmitis
  • Presumed ocular histoplasmosis syndrome
    • Posterior uveitis with choroidal scars
    • Neovascularization/loss of central vision
Cryptococcus
  • Ocular palsies
  • Papilledema
  • Keratitis
  • Endophthalmitis
Candida
  • Fungal keratitis
  • Endophthalmitis
Coccidioides

N/A

Blastomyces N/A
Trichosporon or Rhodotorula

N/A

Otorhinolaryngologic
Histoplasma

N/A

Cryptococcus
  • Gingivitis
  • Sinusitis
  • Salivary gland enlargement
Candida
  • Thrush
  • Nasal ulcers
  • Otitis externa
Coccidioides

N/A

Blastomyces N/A
Trichosporon or Rhodotorula

N/A

Central Nervous System
Histoplasma
  • Chronic meningitis
  • Cerebritis and mass lesion
Cryptococcus
  • Meningitis
  • Intracranial abscesses
  • Spinal granuloma
Candida
  • Meningitis
  • Diffuse microabscesses in brain
Coccidioides

Chronic meningitis with indolent course

Blastomyces
  • Abscesses
  • Meningitis
Trichosporon or Rhodotorula

N/A

Hepatosplenic or Gastrointestinal
Histoplasma
  • Hepatosplenomegaly
  • Chronic granulomatous hepatitis
Cryptococcus
  • Disseminated yeast infections
    • Hepatitis
    • Peritonitis
    • Nodular/ulcerated lesions of colon
Candida
  • Disseminated yeast infections
    • Esophagitis
    • Gastrointestinal ulcers
    • Peritonitis
    • Hepatic and splenic abscesses
Coccidioides

N/A

Blastomyces

N/A

Trichosporon or Rhodotorula

N/A

Dermatologic
Histoplasma

Discrete erythematous skin papules in HIV patients

Cryptococcus
  • Papules
  • Subcutaneous abscesses
  • Purpura
  • Bullae
  • Ulcers
  • Draining sinuses
Candida
  • Folliculitis (generalized cutaneous form)
  • Disseminated skin infections
    • Intertrigo
    • Paronychia
    • Onychomycosis
    • Diaper rash
    • Vaginitis
    • Chronic mucocutaneous candidiasis
Coccidioides
  • Maculopapular to verrucous lesions
  • Subcutaneous abscesses
  • Reactive eruptions (contain no organisms)
    • Erythema nodosum
    • Erythema multiforme
    • Toxic erythema
    • Sweet syndrome
Blastomyces
  • Verrucous or ulcerative lesions
  • Subcutaneous nodules
Trichosporon or Rhodotorula
  • Red papular lesions (T)
  • Catheter-related fungemia (R)
Bone
Histoplasma

Osteomyelitis

Cryptococcus

Osteolytic lesions with soft-tissue abscesses

Candida

  • Osteomyelitis (most common in spine, wrist, femur, ribs, scapula, and proximal humerus)
  • Arthritis

Coccidioides

  • Osteomyelitis (most common in knees, hands, vertebrae, and long bones)
  • Symmetric arthritis (referred to as desert rheumatism)
Blastomyces

Osteomyelitis (most common in long bones, vertebrae, and ribs)

Trichosporon or Rhodotorula

N/A

Genitourinary
Histoplasma
  • Epididymitis
  • Testicular and prostatic abscesses (rarely symptomatic)
Cryptococcus
  • Prostatitis
  • Renal abscesses
  • Genital lesions

Candida

  • Vulvovaginitis
  • Balanitis
  • Papillary necrosis
  • Fungus ball
  • Perinephric abscess

Coccidioides

N/A

Blastomyces
  • Prostatitis
  • Epididymitis
Trichosporon or Rhodotorula
  • Hematuria (T)
  • Funguria (T)

ARUP Lab Tests

Gold standard test to diagnose fungi as agent of infection

Notify laboratory if Malassezia furfur is suspected

Identify fungus from fungal smear (eg, yeast, aseptate hyphae, septate hyphae)

Gold standard test to diagnosis fungi as agent of infection in blood

Identify fungi from culture

For the direct detection and identification of fungi in tissue

Aid in diagnosis of histoplasmosis

Recommend testing in conjunction with combined complement fixation and immunodiffusion antibody and urine galactomannan antigen tests

Crossreactivity with Blastomyces dermatiditis, Coccidioides immitis, and possibly Talaromyces marneffei have been observed

Aid in diagnosis of histoplasmosis

Recommend testing in conjunction with combined complement fixation and immunodiffusion antibody and serum antigen tests

Rapid test for identifying H. capsulatum (yeast or mold form) from pure isolate

Identify C. neoformans as the infectious agent of invasive cryptococcal disease

Identify Cryptococcus as an etiological agent of meningitis

CAP requires confirmation by culture for this test; order with CSF culture and gram stain

When test is ordered by the University of Utah Hospital, Huntsman Cancer Hospital, or VA Hospital of SLC, CSF culture will be ordered automatically; other clients should order culture separately

Aid in diagnosis of invasive/disseminated fungal infections (eg, P. jirovecii, Aspergillus, or Candida)

Does not detect fungal species that produce very low levels of (1-3) beta-D-glucan (eg, Cryptococcus)

Does not detect Zygomycetes (ie, AbsidiaMucor, and Rhizopus)

Yeast phase of Blastomyces dermatitidis may not be detected

Use to detect common vaginal pathogens associated with vaginitis/vaginosis

Not recommended as stand-alone test for sexually transmitted infection testing or screening

Panel includes testing for Candida species, Gardnerella vaginalis, and Trichomonas vaginalis

Preferred serology test to detect coccidioidomycosis (Valley fever)

Panel includes Coccidioides antibody IgG and IgM, Coccidiodes immitus antibodies, and coccidiode titer

Aid in diagnosis of coccidioidal meningitis (Valley fever)

Rapid test for identifying C. immitis (yeast or mold form) from a pure isolate

Rapid test for identifying B. dermatitidis (yeast or mold form) from a pure isolate

Diagnose and monitor B. dermatitidis

For urine specimens, refer to Blastomyces antigen quantitative by EIA, urine

Diagnose and monitor B. dermatitidis

For serum specimens, refer to Blastomyces antigen quantitative by EIA

Recommended test if serology is used to aid in diagnosis of blastomycosis

Recommended test if serology is used to aid in the diagnosis of cerebral blastomycosis

Detect respiratory pathogens in patients with pneumonia

Related Tests

Not recommended

Refer to individual fungus-related tests appropriate to patient exposure

Identify fungi from culture

Determine in vitro susceptibility to antifungal agents for fungal organisms

Agents tested – amphotericin B, anidulafungin, caspofungin, fluconazole, 5-fluorocytosine, itraconazole, micafungin, posaconazole, and voriconazole

Not recommended as a stand-alone test

Refer to combined complement fixation and immunodiffusion test 

Limited clinical utility

Best evidence for infection is significant change on 2 appropriately timed specimens where both tests are done in the same laboratory at the same time; however, low levels of IgM may occasionally persist for >12 months

Preferred test for establishment of diagnosis is Coccidioides Antibody Reflexive Panel

Panel includes coccidioides antibody by CF; coccidioides immitis antibodies by immunodiffusion; coccidioides antibody, IgG and IgM by ELISA

May aid in diagnosis of coccidioidomycosis (Valley fever)

Preferred test for establishment of diagnosis is Coccidioides Antibody Reflexive Panel

Aid in diagnosis of coccidioidal meningitis (Valley fever)

Aid in diagnosis of coccidiodomycosis (Valley fever)

Titers may aid in monitoring coccidioidomycosis (Valley fever) and treatment response

Preferred test for establishment of diagnosis is Coccidioides Antibody Reflexive Panel

Titers may aid in monitoring coccidioidal meningitis (Valley fever) and treatment response

Not recommended

Preferred test for establishment of diagnosis is Coccidioides Antibody Reflexive Panel

Not recommended

Not recommended as a stand-alone test

Preferred test for establishment of diagnosis is Coccidioides Antibody Reflexive Panel

Not recommended as a stand-alone test

Aid in diagnosis of histoplasmosis

Recommend testing in conjunction with serum antigen and urine galactomannan antigen tests

Medical Experts

Contributor

Couturier

Marc Roger Couturier, PhD, D(ABMM)
Associate Professor of Clinical Pathology, University of Utah
Medical Director, Parasitology/Fecal Testing, Infectious Disease Antigen Testing, Bacteriology, and Molecular Amplified Detection, ARUP Laboratories
Contributor

References

Additional Resources
Resources from the ARUP Institute for Clinical and Experimental Pathology®