2. INTRODUCTION
• Infections of the central nervous system (CNS) are serious
and potentially life-threatening.
• Causative agents :
•bacteria, viruses, fungi, spirochetes, or parasites.
•Presumptive diagnosis based on the
•patient’s age,
•presence of risk factors,
•clinical presentation,
•physical examination,
•local epidemiology of CNS infections, CSF analysis,
radiologic studies.
• Specific causative agent: identified by laboratory testing.
3. INTRODUCTION (CONT..)
•The epidemiology of bacterial meningitis has changed over .
•There has been a dramatic reduction in the incidence of
meningitis caused by Haemophilus influenzae type b
organism.
• Streptococcus pneumoniae has become the leading cause of
bacterial meningitis among children less than 5 years of age.
• Inclusion of pneumococcal vaccination in the routine
immunization schedule for children, universal screening of
pregnant women for group B Streptococcus (GBS), and the
availability of newer meningococcal vaccines, there has been
a further reduction in the incidence of bacterial meningitis.
4. Anatomic Organization
•CNS encompasses: brain, spinal cord,
cranial nerves,
• The brain and spinal cord are
protected by the skull and vertebral
column respectively and three layers of
meninges—the dura, arachnoid, and pia
mater.
•The dura mater is a thick, fibrous, white
membrane firmly adherent to skull.
• Deep to the dura mater is the
arachnoid mater, followed by the pia
mater.
5. Anatomic Organization (cont…)
•The subarachnoid space between the arachnoid and Pia
mater is occupied by surface blood vessels and CSF.
• CSF is produced by filtration and secretion from specialized
capillary tufts of the choroid plexus in the four ventricles of the
brain.
• CSF flows from the two lateral ventricles to the third ventricle
and enters the fourth ventricle via the aqueduct of Sylvius.
• From here, CSF enters the basal cisterns and circulates over
the cerebellum and convexities of the cerebral hemispheres.
• CSF is absorbed primarily by the arachnoid villi through tight
junctions of the endothelium.
6. •CSF: clear, colorless, and sterile fluid.
• In normal adults,
CSF volume: 90 to 150 mL,
protein level: 15 to 45 mg/dL,
glucose level: 40 to 80 mg/dL.
• In normal adults, CSF contains
•leukocytes: 0-7/ul,
•DLC
•60-80% lymphocytes,
•10-40% monocytes,
•0-15%neutrophils.
.
Cerebrospinal Fluid Characteristics
7. Cerebrospinal Fluid Characteristics
•Compared with adults, normal newborns have higher CSF
concentrations of
•protein (15 to 150 mg/dL),
•glucose (30 to 120 mg/dL), and
•leukocytes (0 to 30 per milliliter), with a greater
percentage of monocytes and neutrophils.
•The paucity of leukocytes and protein (including
immunoglobulins) in CSF provides little initial defense
against invading organisms.
• Infections of the CNS are frequently, but not invariably,
associated with an increase in CSF cell count (pleocytosis)
and alterations in glucose and protein levels.
8. Host-Pathogen Relationships
•Infection results from the complex interplay among the
host, organism, and environment.
• Host risk factors that predispose to infection include
•extremes of age;
•nutritional and immunologic status;
•co morbidities, such as alcoholism, diabetes mellitus,
malignancy, renal failure, and head trauma; and
neurosurgical procedures.
• Structural components of the organism, such as
capsule,pili, and fimbriae, which mediate adherence to
respiratory tract epithelial cells, play an important role in
meningeal infection.
9. Host-Pathogen Relationships (CONT..)
• Additionally, the bacterial capsule can resist
•neutrophil phagocytosis and
•complement-mediated bactericidal activity,
•thus enhancing survival in the bloodstream.
• Host defenses include the
•presence of mucosal immunity mediated via
immunoglobulin A (IgA) antibody,
•complement activation,
•the presence of organism-specific antibodies.
10. C N S Infections - Meningitis
• Acute meningitis is commonly caused by bacteria (e.g.,
S. pneumoniae,Neisseria meningitidis, H. influenzae,
Listeria monocytogenes) or viruses (e.g., enteroviruses
[EVs], herpesvirus, mumps virus).
• Less commonly, it is caused by other organisms, such as
fungi (e.g., Cryptococcus neoformans), spirochetes (e.g.,
Treponema pallidum, Borrelia burgdorferi), protozoa (e.g.,
Naegleria fowleri), or helminths
• Patients with acute meningitis usually have fever,
headache, vomiting, photophobia, and altered mental status.
• In infants and children, irritability, restlessness, and poor
feeding may be the only signs of meningitis. Untreated
meningitis can result in obtundation, coma, and death.
11. Bacterial Meningitis
•The likely causative agents of bacterial meningitis depend on
the age of the patient and on host factors, such as immune
status, presence of a cerebrospinal leak, or presence of a
foreign body, such as a ventriculo peritoneal shunt.
12. Pathogenesis
• Bacterial infection of the leptomeningeal space can occur
from a distant focus
•via the bloodstream or
•by direct invasion from a contiguous focus of infection
(e.g. mastoid or paranasal sinuses) or
•as a result of neurosurgical procedures.
• Most commonly, infection or colonization of the respiratory
tract is followed by invasion of blood from a respiratory focus
and seeding of the meninges.
• Once in CSF, bacteria replicate, release bacterial
components, and cause an inflammatory reaction.
13. Pathogenesis (CONT..)
•S. pneumoniae, a gram-positive diplococcus, is the most
common cause of meningitis in adults and in children .
• > 90 serotypes, only a few serotypes—including 4, 6B, 9V,
14, 18C, 19F, and 23F—accounted for most cases of
invasive childhood pneumococcal infections
•Patients with sickle cell anemia, those who have
undergone splenectomy or have asplenia, and those
with malignancy, malnutrition, and chronic renal or liver
disease are more likely to develop serious pneumococcal
disease.
14. Pathogenesis (CONT..)
•Two pneumococcal vaccines are available for use in adults
and children:
(1) the 13-valent pneumococcal conjugate vaccine
(PCV13),
which is composed of purified polysaccharides of 13
serotypes conjugated to a nontoxic variant of diphtheria
toxin carrier protein,CRM197
(2) the 23-valent vaccine (PS23), composed of 23 purified
capsular polysaccharides.
15. Pathogenesis (CONT..)
• H. influenzae type b, a gram-negative coccobacilli, is an
important cause of bacterial meningitis in children. Most cases
were caused by the capsular type b strains.
• In addition to meningitis, it can cause otitis media,
pneumonia, and epiglottitis.
• Previously it was the most common cause of bacterial
meningitis, especially in young children.
•Since the adoption of the routine use of conjugate vaccines
against H. influenzae type b,there has been a marked
reduction in the number of cases of H. influenzae meningitis.
• In developing countries with limited vaccine coverage,
however, it continues to be an important cause of bacterial
meningitis.
16. • N. meningitidis, a gram-negative diplococcus , is
classified into 12 serogroups based on antigenically
distinct, non–cross-reactive capsular polysaccharides.
•Serogroups A, B, C, X, Y, and W135 account for most
cases of meningococcal disease throughout the world.
•Disease attributable to sero group A is seen in Asia and
Africa but is rare in industrialized countries.
•Disease caused by serogroups A and C can occur in
epidemics.
17. • L. monocytogenes is a gram-positive rod.
• Infection by this organism is usually seen in pregnant
women, neonates, older adults, people with alcoholism,
and persons with impaired cell-mediated immunity.
• Outbreaks of Listeria infection have been associated
with the consumption of contaminated coleslaw, milk,
ice cream, and cheese.
• Patients with meningitis caused by Listeria have low CSF
leukocyte counts, with a predominance of lymphocytes.
18. •Streptococcus agalactiae (or GBS) is a gram-positive
coccus that is often isolated from rectal or vaginal cultures of
asymptomatic pregnant women.
• Early-onset GBS disease usually occurs within the first 24
hours of life and is not commonly associated with meningitis
(5% to 10% of cases).
• Late-onset disease, which typically occurs at 3 to 4 weeks of
age (range 7 to 89 days),commonly manifests itself as occult
bacteremia or meningitis(approximately 30% of cases).
• Approximately 50% of survivors of early- or late-onset
meningitis have long-term neurologic sequelae.
19. •Nosocomial transmission via the hands of health care
workers has also been described.
• Most cases of neonatal meningitis are caused by
serotype III.
• Risk factors for GBS infection in adults include age
greater than 60 years, diabetes mellitus, and underlying
malignancy.
20. • Aerobic gram-negative bacilli, such as Escherichia coli,
Klebsiella spp. , Acinetobacter baumannii, Pseudomonas
aeruginosa, Serratia spp., and Salmonella spp., can also
cause meningitis.
•In addition to neonates, older adults, patients with
head trauma, or those who have undergone neurosurgical
procedures are also at risk of meningitis caused by these
organisms.
• Most strains of E. coli that cause meningitis possess the K1
antigen.
21. Other Bacteria: Meningitis caused by S. aureus,CONS,
and Granulicatella spp.
usually occurs in patients who have undergone recent
neurosurgical procedures or in those with CSF shunts.
• Meningitis caused by enterococci or group A streptococci are
not commonly seen.
• Meningitis caused by anaerobic streptococci, Bacteroides
spp. , and Fusobacterium spp. is uncommon and is
usually associated with a concurrent brain abscesses or a
contiguous focus of infection.
22. Shunt Infections
• Generally, CSF shunts are placed in patients with
hydrocephalus or other CNS lesions that interfere with the flow
of CSF.
•The proximal end of the shunt is in the cerebrospinal space,
and the distal end is in the peritoneal, pleural, or vascular
space.
•Patients with shunts are at risk of developing infections.
Staphylococci account for two thirds of CSF shunt infections,
with coagulase-negative staphylococci being the most
common,
followed by S. aureus. Gram-negative organisms, such as E.
coli,
Klebsiella spp., and Proteus spp., also can cause CSF shunt
infections.
23. • Recently, an increasing incidence of CSF shunt infections
from Propionibacterium acnes has been reported.
• Immunosuppressed patients can develop CSF shunt
infections with Candida spp.
• CSF shunts terminating in the peritoneal cavity have a
greater risk of infection with gram-negative organisms; mixed
infections are seen when the catheter perforates a hollow
viscus.
24. • Viruses are the most frequent cause of aseptic meningitis,
a condition characterized by a lymphocytic pleocytosis in
CSF and lack of an identifiable causative agent after routine
stains and culture of CSF .
•The most common viruses producing aseptic meningitis
include EVs and herpesviruses.
• Less common causes of viral aseptic meningitis include
mumps virus, lymphocytic choriomeningitis virus (LCMV), and
HIV
•Viral pathogens colonize various mucosal surfaces in the
body, such as the respiratory and GI tracts.
25. • Some viruses—for example, EVs, adenoviruses, and
parvovirus—can resist inactivation by gastric acid.
• After initial replication at the site of mucosal
colonization, viremia develops, followed by invasion of
the CNS.
• Early viral infections may show a predominance of
neutrophils in CSF, but the pleocytosis rapidly progresses
to a lymphocytosis.
26. • Determination of a specific causative virus associated with a
CNS infection is difficult because of the following:
(1) a large number of different viruses involve the CNS;
(2) viruses may come from endogenous reactivation or
exogenous infection;
(3) many viruses produce a spectrum of neurologic complaints;
and
(4) the magnitude of any neurologic illness resulting from
viruses may depend on the age and immune status of the
patient as well as other undefined factors.
.
27. •The determination of a specific viral cause can often be
made through
-carefully obtaining the patient’s history,
- selected serologic tests (e.g., determination of virus-specific
immunoglobulin M [IgM]
- of a fourfold or greater rise in antibody titer between acute-
phase and convalescent-phase sera),
-viral culture or polymerase chain reaction (PCR) assay for
selected viruses,
- tissue biopsy for routine light microscopy,
- immunofluorescence, or ultra structural studies.
• Viruses isolated from body sites other than the CNS may be
implicated in CNS syndromes.
•Appropriate specimens for culture include nasopharyngeal
swabs, urine, stool, tissue, and occasionally blood
28.
29. Mycobacterial Infections
•The most common mycobacterial infection of the CNS is
tuberculous meningitis caused by M. tuberculosis.
• Other mycobacteria associated with CNS infections include
Mycobacterium bovis, M. avium, M.intracellulare,
M. kansasii, M. fortuitum, M,abscessus, and M. africanus.
• Mycobacteria are acid-fast bacilli with a thick cell wall
containing lipids, peptidoglycans ,and arabinomannans.
• The bacilli enter the body through respiratory droplets and
multiply in the alveolar spaces or macrophages.
• Spread to extra pulmonary sites occurs via blood.
•HIV infection is a risk factor for tuberculous meningitis.
30. • Tuberculous meningitis results when the brain
tubercle ruptures into the subarachnoid space.
• Both the meninges and the brain itself are frequently
involved, with a resulting thick exudate, especially at the
base of the brain.
• The clinical presentation of tuberculous meningitis is
subacute and includes fever, headache, meningismus,
and mental changes.
• Vomiting and other signs of increased intracranial
pressure may occur.
31. Spirochete Infections
The spirochetes associated with CNS infection are T. pallidum
and B. burgdorferi.
T. pallidum, the causative agent of syphilis, enters the CNS
during early infection and can be isolated from CSF in patients
with primary syphilis.
Many cases of neurosyphilis are reported in patients with HIV
infection.
Manifestations of neurosyphilis can occur at any stage of
infection, especially in patients with HIV infection. Syphilitic
involvement of the CNS can take one of four forms—syphilitic
meningitis, meningovascular syphilis, parenchymatous
neurosyphilis, and gummatous neurosyphilis.
32. •Involvement of the CNS can occur in patients with Lyme
disease.
• It is usually seen in patients with early disseminated disease
and is less likely during late disease.
• Not all cases of Lyme meningitis are preceded by the
characteristic erythema migrans rash.
• In addition to signs of meningeal irritation, some patients
with Lyme meningitis can have other neurologic
manifestations of Lyme disease, such as cranial nerve
neuropathy (commonly cranial nerve CN VII) and
radiculoneuritis.
33. Fungal Infections
Fungi are uncommon causes of CNS infections.
The risk factors for CNS fungal infections include
immunocompromised state, organ transplantation, and
diabetes.
Aspergillus and Cryptococcus species are the most
common etiologic agents in immunosuppressed patients.
Other etiologic agents include Coccidioides immitis,
Histoplasma capsulatum, and Blastomyces dermatitidis.
Concurrent infections with C. neoformans and H.
capsulatum have been reported in immunocompromised
persons.
34. Fungal Infections (CONT..)
Recent outbreaks caused by Cryptococcus gattii have been
reported in the Pacific Northwest of the United States in
previously healthy individuals.
Rare cases of meningeal sporotrichosis caused by
Sporothrix schenckii have been reported.
The clinical presentation is usually of chronic meningitis.
The white blood cell count is usually moderately elevated,
with a predominance of lymphocytes.
A predominance of eosinophils may occur in infections
caused by Coccidioides organisms.
35.
36. C. neoformans is an encapsulated basidiomycetous yeast.
It can spread hematogenously to the CNS from pulmonary
foci and cause chronic meningitis, particularly in patients with
AIDS.
There are two varieties of C. neoformans: C. neoformans var.
neoformans and C. gattii (formerly known as C. neoformans
var. gattii) C. neoformans var. neoformans is the major isolate
in patients with AIDS and consists of serotypes A and D. C.
gattii is restricted to tropical and subtropical regions and
consists of serotypes B and C.
The number of organisms in the CSF may be small in
immunocompetent patients but large in immunosuppressed
patients
37. C. immitis is a dimorphic fungus that causes chronic
meningitis.
Infections caused by C. immitis are limited to endemic
regions, mainly the southwestern United States, Mexico, and
Central and South America. Human infection occurs via
inhalation of arthroconidia.
B. dermatitidis is a dimorphic fungus. Inhalation of conidia
results in pulmonary infection, which may spread to the CNS
and cause an abscess or fulminant meningitis. It is endemic in
the Mississippi and Ohio river basins. H. capsulatum is also a
dimorphic fungus.
38. •Candida spp. are the cause of fungal meningitis and
cerebral abscesses.
•They are mainly seen in patients with invasive or
disseminated candidiasis.
•Candidiasis may be acquired as a nosocomial infection in
patients with indwelling catheters or those receiving
antibacterial therapy.
• CNS infection with Candida spp. can occur in patients
•with ventriculoperitoneal shunts.
• Patients with low peripheral blood neutrophil counts
secondary to chemotherapy are at risk for candidal
infections.
• C. albicans, C. tropicalis, and C. parapsilosis are the most
commonly identified species.
39. Parasitic Infections
The protozoa and helminths can invade the CNS and cause
meningitis. Some parasites cause CNS lesions without
obvious meningeal inflammation.
The free-living amebae that can infect humans
include N. fowleri, Acanthamoeba spp., and Balamuthia
mandrillaris.
Trophozoites invade the nasal epithelium and migrate to
the CNS via the olfactory nerve.
N. fowleri can cause a rapidly progressive and almost
always fatal primary amebic meningoencephalitis.
Acanthamoeba spp. and B. mandrillaris usually cause
granulomatous amebic encephalitis
40. • Cerebral malaria is an acute illness that occurs because of
sequestration of the parasite Plasmodium falciparum in the
CNS.
•Toxoplasma gondii is a coccidian, obligate, intracellular
protozoan.
•Trypanosomes that infect humans include Trypanosoma brucei
subsp. gambiense, Trypanosoma brucei subsp. rhodesiense,
and Trypanosoma cruzi.
41. Laboratory Diagnosis
The diagnosis of CNS infections is based on examination of
CSF samples obtained by lumbar puncture.
Blood cultures are often helpful in identifying the causative
microorganism.
The CSF sample is obtained by inserting a sterile hollow
needle into the spinal subarachnoid space in the lower
(lumbar) back .
Lumbar puncture is often performed after computed
tomography (CT) in patients with elevated intracranial
pressure or focal neurologic lesions because of the risk of
brain herniation.
In patients with brain abscesses, aspirates and tissue
samples are helpful because CSF may be normal.
42.
43. Transport and Analysis
• The CSF samples should be transported to the laboratory
without delay and processed as soon as possible to prevent
loss of viability of the causative agent.
• If delay cannot be avoided, CSF samples should be stored
at room temperature until processed (within 24hours).
• For viral testing, CSF samples may be stored at 2° to 8° C
in the short term (<48 hours) and at −70° C in the long term.
•When large volumes (>1 mL) of CSF sample are available,
concentration by centrifugation increases the yield of
microorganism for microscopic examination and culture.
• It is standard to obtain three to four tubes of CSF, each
containing 1 or 2 mL of fluid.
44. Cultures are performed on samples that have the least
likelihood of contamination (second or third tube).
The CSF is analyzed for glucose and protein concentration,
cell counts, and identification of the causative agent by Gram
stain, culture, antigen detection, and PCR assay.
Meningitis is suspected from the presenting clinical
symptoms, findings on physical examination, and
initial CSF studies, including visual inspection, chemical
analysis, and cell counts.
45. • The characteristic CSF laboratory findings for various
causative agents are compared in .
• The CSF white blood cell counts in neonates may not
be helpful in the diagnosis of bacterial meningitis.
• Acid-fast staining and negative staining are useful in
the diagnosis of Tuberculous and cryptococcal
meningitis, respectively.
46. Culture
• Isolation of fastidious organisms would require special
medium and incubation conditions.
• Anaerobic bacteria rarely cause meningitis but are
commonly associated with brain abscesses.
•Transport media, such as the modified Stuart medium or
Amies medium, are generally sufficient for isolation of most
microorganisms, including anaerobes.
• Sheep blood and chocolate agar incubated in 3% to 5%
carbon dioxide (CO2) is usually used for bacterial culture of
CSF.
• When CSF samples are collected from shunts, broth media
should also be inoculated.
47. Molecular Diagnostics
•The Film Array meningitis/encephalitis (ME) panel is a
multiplexed in vitro diagnostic test that can be used to detect
14 pathogens (E. coli K1, H. influenzae, L. monocytogenes, N.
meningitidis, S. pneumoniae, S. agalactiae, CMV, EV, HSV-1,
HSV-2, HHV-6, HPeV, VZV, and C. neoformans/C. gattii)
simultaneously in CSF samples.
• The panel allows rapid detection (1 hour) with good
sensitivity and specificity.
• Gram stain and culture will still need to be conducted to
identify pathogens not covered by the panel.
• Next-generation sequencing (NGS), a research technology,
can aid in the identification of viral agents of CNS infections,
especially when traditional diagnostic methods fail.
48. Observations in Bacterial Infections
In acute bacterial meningitis, CSF is turbid or cloudy because
protein levels are significantly raised.
Glucose levels are very low (<40% of the serum glucose
concentration) in most patients with bacterial meningitis.
The gold standard for diagnosis of bacterial meningitis is
culture of CSF.
Antibiotic exposure reduces the sensitivity of culture. Staining
techniques are rapid but less sensitive than culture.
The sensitivity of Gram stain ranges from 40% to 90%,
depending on whether the patient received antimicrobial
therapy prior to lumbar puncture
49. Latex agglutination tests for the detection of H. influenzae
type b, S. pneumoniae, GBS, and N. meningitidis are
available; however, these kits do not detect group B
meningococci and CONS.
False-positive results can occur because of cross-reactivity
with other bacterial species.
False-negative results have been observed in specimens
from pregnant women and infants.
Routine use of antigen detection methods for diagnosis of
bacterial meningitis is of limited value because the
performance of the antigen test is similar to that of Gram
stain, and a positive antigen test result usually does not alter
the course of therapy.
50. • However, bacterial antigen testing may be beneficial in
cases in which cultures are negative and clinical
suspicion of bacterial meningitis is high or in cases of
partially treated meningitis with sterile cultures.
• Multiplex PCR assays for the simultaneous detection of
N. meningitides, H. influenzae, and S. pneumoniae and
for serogrouping are being developed.
• These multiplex PCR assays are used in conjunction
with traditional detection methods.
51. Viral Infections
In viral infections, the number of lymphocytes in CSF↑.
The diagnosis of viral meningitis is based on detection of viral
genome by PCR assay or antigen detection by fluorescent
antibody or enzyme immunoassay (EIA).
The sensitivity of viral culture
- 14% to 24% VS 88% to 94% with PCR,
- PCR the method of choice
The sensitivity and specificity of PCR assays can vary in relation
to the virus being tested.
Cell culture is recommended for EVs. Recently, the GeneXpert
EV assay (Cepheid, Sunnyvale, CA), a real-time multiplex PCR
assay for the detection of EV RNA in CSF, has become
available.
A positive result with the GeneXpert EV assay does not rule out
other causes of meningitis.
52. •The results from this assay should be interpreted in
conjunction with available clinical and laboratory information.
• For HSV, diagnosis includes detection of HSV DNA in CSF by
PCR assay, growth of HSV on culture, antigen detection in
brain biopsy samples, and demonstration of antibody in CSF
and serum.
• Antigen and antibody assays have low sensitivity and are
positive in the later stage of the disease.
• Although the PCR assay is highly sensitive, a false-negative
result may be obtained in CSF samples obtained within the first
48 hours of illness.
• Repeated testing is helpful in such cases.
53. Mycobacterial Infections
•Tuberculous meningitis is characterized by elevated
lymphocyte, elevated protein, and reduced glucose levels.
• The gold standard for diagnosis is identification of
mycobacteria in the CSF by acid-fast staining and culture.
•Broth medium (e.g., Middlebrook 7H9, Dubos) and solid
agar medium (e.g., Middlebrook 7H11, Löwenstein-Jensen)
are used routinely to culture mycobacteria but require a
long incubation period.
• Use of the mycobacterial growth indicator tube or other
automated systems, such as the MB/BacT (Organon
Teknika, Durham, NC), ESP (Trek Diagnostic Systems,
Westlake, OH), BACTEC9000 TB series, or BACTEC460
can increase recovery and reduce the time to detection of
mycobacteria in CSF.
54. Mycobacterial Infections (cont..)
•Staining positivity : -10% to 22% of cases,
•cultures positivity: - 38% to 88% of cases.
• The number of mycobacteria in CSF is usually small;
therefore concentration of the CSF sample is useful in
increasing recovery of the bacteria.
•Other techniques, such as the detection of mycobacterial
antigen, antimycobacterial antibodies, or mycobacterial
DNA by PCR assay, may be helpful.
•The PCR assays should be used in conjunction with
culture.
55. Spirochetes Infections
Lyme meningitis is also characterized by elevated
lymphocyte, elevated protein, and reduced glucose levels.
In symptomatic patients, diagnosis is made by using EIA or
immunofluorescent assay (IFA) followed by a Western
immunoblot.
56. Fungal Infections
•Direct microscopic examination of
•Gram-stained
•India ink–stained CSF samples,
•calcofluor-stained tissue samples,
• culture
• Concentration methods can increase the sensitivity of
fungal staining and culture.
•Several media are available for fungal cultures of CSF or CNS
tissue. - incubated for 4 to 6 weeks.
57. •Antigen detection by a latex agglutination test is useful in the
case of infections- C. neoformans and H. capsulatum.
•. CSF and serum galactomannan levels are useful for the
diagnosis of Aspergillus infections.
• Antibody detection using the complement fixation assay and
immunodiffusion is useful for the diagnosis of C. immitis.
•PCR tests for routine detection of fungal DNA are not
standardized.
58. Parasitic Infections
•The identification of parasitic causes of CNS infections is
usually based on microscopic examination of Giemsa- or
calcofluor-stained aspirate or biopsy samples .
• Culture using agar with bacterial overlay is recommended for
free-living amebae, such as Naegleria and Acanthamoeba, but
not for B. mandrillaris.
•Serology and PCR testing are available for detection of
Toxoplasma.
• Antibody detection by immunoblot is used as an adjunct
serologic test for confirmation of radiologic diagnosis in patients
with neurocysticercosis(NCC serology)
59. • Diagnosis of human trypanosomiasis is mainly via examination
of unstained and Giemsa-stained blood smears, lymph node
aspirates, marrow, or CSF for trypomastigotes.
•Concentration techniques using quantitative Buffy coat analysis
tubes increase the sensitivity of detection of
•the parasite.(Plasmodium falciparum in the CNS)
• Hematocrit centrifugation and anion exchange column
•chromatography also increase the sensitivity of parasite
detection.
•Examination of CSF processed by a double-centrifugation
technique often reveals trypanosomes in patients in the late
stage of the disease
