Table 3. . Comparison of major commercially available or investigational diagnostic tests by meningitis etiology.
| Test | Description | Time to Results | Advantages | Disadvantages | Comm. Avail. | Ref. |
|---|---|---|---|---|---|---|
| Bacterial | ||||||
| Gram stain | Stain of fluid for bacteria | 1 h | Cheap, easy to perform | sensitivity ∼90% prior to antibiotics for S. pneumoniae meningitis | yes | |
| Culture | Standard bacterial culture | 1–3 days | May grow quickly, easy to perform, adaptable to rapid identification methods | Yield decreased by antibiotic use prior to culture, may be days to results, variable sensitivity | yes | |
| Procalcitonin, C reactive protein | Serum biomarkers | 1 h | Good differentiation between bacterial and aseptic meningitis | Cost, lab requirements, no studies on TBM or CM | yes | |
| Lactate | Biomarker measure in CSF | <5–60 min | Rapid, sensitive and specific if obtained prior to antibiotics | Not very sensitive if measured after antibiotics are given | yes | [170] |
| 16s rRNA PCR | PCR detection of 16s ribosomal RNA to elicit specific pathogens | Hours | Rapid, more sensitive than culture, very specific | Extremely costly, requires lab expertise and infrastructure | Yes | |
| Nucleic acid amplification tests | Specific RT-PCR and LAMP assays have been tested for particular pathogens | 1–2 h | Rapid, specific, potentially quite sensitive | Cost, lab infrastructure, lack of large studies | In some cases | |
| Rapid diagnostic tests | Rapid, usually card or dipstick-based tests for specific etiologies | <15 min | Rapid, cheap, easy to use, no significant lab infrastructure necessary | Variable specificity, sensitivity | yes | |
| MALDI-TOF MS | Mass spectrometry identification based on weight | 1–2 h | Rapid, relatively inexpensive | Requires significant laboratory infrastructure, not widely used on CSF at this time | Yes, blood only | |
| Mycobacteria tuberculosis | ||||||
| Ziehl–Neelsen stain | Staining for acid-fast bacilli | 1 h | Cheap | Very insensitive, minimal utility. Extremely technician dependent | yes | |
| LJ culture | Traditional culture, solid media | 3–5 weeks | Reliable, somewhat sensitive | Very slow growth, still many false negatives, costly, labor intensive | yes | |
| MGIT culture | Liquid-based culture | 1–2 weeks | As sensitive and quicker than LJ culture | ∼2 weeks to growth, costly | yes | |
| Adenosine deaminase activity (ADA) | Detectable enzyme released by during T cell activation | <1 h | Rapid, low cost | Variable sensitivity and specificity, lab infrastructure | yes | |
| Interferon gamma release assay (IGRA) | IFN-g secretion by host memory T cells on exposure to TB antigens | 24–36 hours | Good sensitivity | Labor intensive, costly, high numbers of indeterminate results, variable studied cut-points, rely on T-cell function | yes | |
| PCR | Traditional PCR | Hours | Fast, nearly as sensitive as culture, specific | Cost, lab expertise, lab apparatus, inadequate sensitivity | yes | |
| LAMP | DNA amplification different from typical PCR, detection by color change | Less lab expertise and infrastructure required than PCR, isothermal | No data on performance | no | ||
| GeneXpert | Cartridge-based PCR | 2.5 h | Quick, similar sensitivity to culture, specific, ease of use | Cost, requires significant infrastructure, limited shelf life on cartridges | Yes | |
| GeneXpert ultra | Cartridge-based PCR | <2 h | Rapid, improved performance versus any commercially available test, ease of use | Cost, lab infrastructure, still not adequate negative predictive value to ‘rule-out’ TB meningitis | Yes | |
| Cryptococcus | ||||||
| CrAg lateral flow assay | Rapid dipstick test detects cryptococcal antigen | 10 min | Very sensitive, specific, cheap, does not require significant lab capacity | Cannot differentiate active from past infection | yes | |
| Culture | Traditional culture | 3–14 days | Very accurate, can decide active from past infection | Slow, labor intensive | yes | |
| CrAg latex agglutination or ELISA | Lab-based detection of cryptococcal antigen | 1 day | Sensitive and specific. Requires lab infrastructure | Costly, lab capacity requirement, + result lingers for years | yes | |
| India ink | Staining for C neoformans capsule | 15 min | Inexpensive, easy to perform | 85% sensitive; Technician dependent |
yes | |
| Histoplasma | ||||||
| Culture | Traditional culture | Weeks | Very accurate, widely available | Slow, low yield | yes | |
| Antibody/ antigen testing | Immunodiffusion, complement fixation, EIA | Hours | Inexpensive | Can be negative early in infections, can cross react with other fungi | yes | |
| Coddidioides | ||||||
| Culture | Traditional culture | Weeks | Very accurate, widely available | Slow, low yield | yes | |
| Wet mount | Direct visualization of organism | <1 h | Inexpensive, easy to perform | Very low yield, requires experienced lab personnel | yes | |
| Antibody/antigen testing | CF, ID, EIA | Hours–days | Inexpensive | Cannot ‘rule out’, cross reactivity with other fungi | yes | |
| Blastomyces | ||||||
| Culture | Traditional culture | Weeks | Very accurate, widely available | Slow, low yield | Yes | |
| Antigen testing | EIA | Days | Minimal performance data, reference lab only | No | ||
| Aspergillus | ||||||
| Culture | Traditional culture | Weeks | Widely available | Slow, low yield, requires multiple samples | Yes | |
| Galactomannan | Detection of Ag to cell wall component | Hours | Widely available | Cross reacts other species and medications | Yes | |
| Aseptic (viral) | ||||||
| 16s rRNA amplification | PCR detection of 16s ribosomal RNA to elicit specific pathogens | Days | Rapid, very specific | Extremely costly, requires lab expertise and infrastructure | Yes | |
| NAATs | Specific PCR and RT-PCR assays for certain pathogens | 1–6 h | Rapid, specific | Cost, lab infrastructure and expertise | In some cases | |
| Syndromic or pan-pathogenic | ||||||
| BioFire film array | PCR panel that detects 14 h pathogens | 1 h | Rapid, specific | Limited to pathogens in the panel costly, lab infrastructure | Yes | |
| Next-generation sequencing | Nucleic acid detection of any pathogen | Days | Specific, unclear clinical role | Only available at one center, costly, lab infrastructure | Yes | |
Test is meant to describe test category, not each specific commercial test. The description notes how the test works in principle. ‘Pro’ and ‘Con’ refer to positive and negative aspects of each tests performance and utility. Assays dealing with M. tuberculosis cells require increased biosafety apparatus.
AFB: Acid-fast bacilli; CF: Complement fixation; Comm. Avail.: Commercially available; CrAg: Cryptococcal antigen; CSF: Cerebrospinal fluid; ID: Immunodiffusion; IFNg: Interferon gamma; LAMP: Loop mediated isothermal amplification; LJ: Lowenstein Jensen; MALDI TOF MS: Matrix-assisted laser desorption/ionization time of flight mass spectrometry; MGIT: Mycobacterial growth indicator tube; NAAT: Nucleic acid amplification test; PCR: Polymerase chain reaction; rRNA: Ribosomal ribonucleic acid.