Table 3.

Comparison of major diagnostic tests commercially available or under investigation for bacterial, viral, cryptococcal and tuberculosis meningitis.

Etiology	Test	Description	Time to Results	Positive attributes	Negative attributes	Commercial availability
Bacterial	Gram stain	Stain for bacteria by microscopy	1 h	Cheap, easy to perform	Sensitivity 70–90% prior to antibiotics for pneumococcal meningitis	Yes
	Culture	Standard bacterial aerobic culture	1–3 days	May grow quickly, easy to perform, adaptable to rapid identification methods	Yield decreased by antibiotics prior to culture, may be days to results, variable sensitivity by organisms	Yes
	Procalcitonin, CRP	Serum inflammatory biomarkers	1 h	Good differentiation between bacterial and aseptic meningitis	Cost, lab requirements, no studies on Cryptococcus or TB (with probable overlap in CRP)	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 given	Yes
	16s rRNA PCR	PCR detection of 16s ribosomal RNA to elicit specific pathogens	Hours to days	Rapid, more sensitive than culture, very specific, rapid automated assays being developed	Extremely costly, requires lab infrastructure and expertise.	Yes
	NAATs	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
	LFA	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 – dependent on quality of monoclonal antibody and target analyte	Yes
Mycobacterium tuberculosis	Ziehl-Neelsen AFB staining	Staining for acid fast bacilli by microscopy	1 h	Cheap	Very insensitive, extremely technician dependent	Yes
	Culture, Löwenstein-Jensen (LJ)	Traditional culture on solid LJ media	3–5 weeks	Reliable, somewhat sensitive	Very slow growth, still many false negatives, costly, labor intensive	Yes
	Culture, MGIT	Liquid based culture	1–2 weeks	As sensitive and quicker than LJ culture	approximately 2 weeks to growth, costly	Yes
	Culture, MODS	Kit based liquid culture	1 week	More rapid than MGIT, detects resistance concurrently	Sensitivity may be slightly less than MGIT and LJ cultures	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)	Interferon-gamma secretion by host memory T cells on exposure to TB antigen	24–36 h	Limited data on CSF	Labor intensive, costly, high numbers of indeterminate results, variable studied cut-points, rely on T-cell function	Yes
	NAATs	Traditional nucleic acid amplification tests such as PCR	Hours	Fast, nearly as sensitive as culture, very specific	Commercially available tests less sensitive than ‘in-house’ tests, cost, lab expertise, lab apparatus	Yes
	LAMP	DNA amplification detected by color change	1 h	Less lab expertise and infrastructure required than typical PCR, isothermal	No data on performance	No
	GeneXpert	Cartridge based, automated PCR	2.5 h	Quick, similar sensitivity to culture, highly specific	Costly, requires significant infrastructure, easy to use Sensitivity related to CSF volume and organism burden	Yes (for use on sputum)
	TB-LAM LFA	Dipstick test detects lipoarabinomannan antigen	25 min	Quick, inexpensive	Insensitive, minimal data on CSF	Yes, urine
Cryptococcus neoformans	CrAg LFA	Dipstick test detects CrAg	10 min	Very sensitive and specific, inexpensive, no lab infrastructure needed	Cannot differentiate active from past infection	Yes
	Culture	Fungal culture on Sabouraud agar	3–14 days	Very accurate, can decide active from past infection	Slow, labor intensive, requires lab infrastructure	Yes
	CrAg latex agglutination or ELISA	Latex agglutination or enzyme immunoassay detection of CrAg	1–48 h	Sensitive and specific. Requires lab infrastructure	Costly, lab capacity requirement, cold chain of reagents, cannot differentiate active from past infection	Yes
	India ink	Staining for C. neoformans capsule by microscopy	15 min	Inexpensive, easy to perform	85% sensitive, requires microscope, technician dependent	Yes
Aseptic (viral)	16s rRNA amplification	PCR detection of 16s rRNA to elicit specific pathogens	Days	Rapid, very specific	Extremely costly, requires lab expertise and infrastructure. Delay in sequencing	Research and reference labs
	NAATs	Specific PCR and RT-PCR assays have been developed for certain pathogens	1–6 h	Rapid, specific, automated assays in development	Cost, lab infrastructure and expertise	In some cases

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 organisms require increased biosafety apparatus.

AFB: Acid-fast bacilli; CrAg: Cryptococcal antigen; CRP: C-reactive protein; CSF: Cerebrospinal fluid; LAMP: Loop-mediated isothermal amplification; LFA: Lateral flow immunochromatographic assay; MGIT: Mycobacteria growth indicator tube; MODS: Microscopic observation drug susceptibility; NAAT: Nucleic acid amplification test.