Diagnostic tests
| Diagnostic test | Advantages | Disadvantages and pitfalls | Recommendations |
| India ink microscopy | Provides rapid result within 10 min Relatively cheap cf. culture methods | Operator-dependent—requires expertise in microscopy Lower sensitivity and specificity for CM than CrAg—particularly in patients with lower fungal load (early in disease course/on ART) Does not provide information on species or antifungal sensitivities | Do not perform unless CrAg unavailable on site |
| Cryptococcal antigen (CrAg) lateral flow assay | Very high sensitivity and specificity in symptomatic patients—confers high negative predictive value Provides rapid result within 10 min Can be performed by staff with minimal clinical and laboratory training—making it cheap and scalable Can be performed on serum samples in patients in whom CSF sample difficult to acquire | Remains positive for months—not useful for monitoring treatment response or diagnosing relapse Titres connoting ‘positivity’ vary between manufacturers Does not provide information on species or antifungal sensitivities | Perform CrAg in all patients with CSF high in lymphocytes and protein and/or low in glucose without an adequate explanation In immunosuppressed patient with contraindication to LP, perform serum CrAg Do not use CrAg to monitor treatment response or diagnose relapse |
| Fungal culture | Identifies viable cells capable of reproduction, signalling active infection when specimen obtained from sterile site High sensitivity and specificity in symptomatic patients Provides detailed information on Cryptococcus species and drug sensitivities | Need for highly-trained staff—expensive and challenging in low-resource settings Unless laboratory is aware that patient is immunocompromised, fungal culture is not carried out routinely—need to notify Calls for energy-intensive and expensive incubation equipment, which may not be available in low-income settings Risk of sterile culture if sample obtained some time after treatment started—false negative result | Where available, fungal culture should be performed for 21 days for all immunocompromised patients and people with sarcoidosis or cancer, with abnormal leucocyte count, protein and/or glucose in CSF CSF fungal culture is the investigation of choice in suspected CM relapse Unless dealing with disease recurrence, antifungal sensitivities have little bearing on treatment |
| Galactomannan | Readily available fungal biomarker—detectable in both serum and CSF | Low sensitivity for CM—most useful in suspected invasive aspergillosis Moderate wait for results—in-house testing of serum samples usually gives result in 24–48 hours | Do not use in assessment of suspected CM |
| Beta D-glucan | Readily available fungal biomarker—detectable in both serum and CSF | Pan-fungal marker—not specific to CM Moderate wait for results—in-house testing or serum and CSF samples usually gives results in 24–48 hours | Do not use in assessment of suspected CM Consider CM as possible cause of raised serum BDG in patients with compatible syndrome |
ART, antiretroviral therapy; BDG, beta D-glucan; CM, cryptococcal meningitis; CSF, cerebrospinal fluid; LP, lumbar puncture.