meningitis

1. Meningitis
Presenter – Dr. Vaishali T
Moderator – Dr. Shyamala R
1

2. Definition
Meningitis is the inflammation of the leptomeninges ( pia and
aarchanoid matter) surrounding the brain and spinal cord, with
involvement of the subarachnoid space.

3. Types of meningitis
Based on the onset
Acute meningitis:
• Progresses in few hours
• Acute bacterial
• Acute viral
Chronic meningitis:
• Progressively worsens over weeks (>4 weeks)
• Bacterial, viral, fungal and parasitic

4. Bacterial meningitis

5. Acute bacterial/pyogenic meningitis
• Bacterial meningitis is an inflammation of the
leptomeninges, usually causing by bacterial infection.
• Bacterial meningitis may present acutely (symptoms
evolving rapidly over 1-24 hours), sub acutely (symptoms
evolving over 1-7days), or chronically (symptoms evolving
over more than 1 week).

6. Epidemiology
6
• Annual incidence in the developed countries is
approximately 5-10 per 100000.
• 30000 infants and children develop bacterial
meningitis in United States each year.
• Approximately 90 per cent of cases occur in
children during the first 5 years of life.

7. Epidemiology
7
• Cases under age 2 years account for almost 75%
of all cases and incidence is the highest in early
childhood at age 6-12 months than in any other
period of life.
• There are significant difference in the incidence
of bacterial meningitis by season.

8. Etiological agents
8
• Acute:
- Streptococcus pneumoniae (38%)
- Neisseria meningitides (14%)
- Hemophilus influenza (4%)
- GNB’s ( E.coli, Klebsiella, Pseudomonas,
Acinetobacter)
- S. agalactiae
- Listeria
- Staphylococcus aureus (5%)
• Chronic:
- Mycobacterium tuberculosis

9. Etiology
Dr.T.V.RaoMD 9
– Elderly and immunocompromised
• Listeria Monocytogenes
• Gram negative bacteria
– Hospital-acquired infections
• Klebsiella
• Escherichia coli
• Pseudomonas
• Staphylococcus aureus

10. Etiology
Dr.T.V.RaoMD 10
Children over 2 months
 Haemophilus influenza type b
 Neisseria meningitides
 Streptococcus pneumoniae
Children over 12 years
 Neisseria meningitides
 Streptococcus pneumoniae

11. Pathogenesis
• Mode of transmission – droplets from respiratory secretions
• Routes of infection:
Hematogenous spread – most common, through choroid
plexus
Direct spread – otitis media, sinusitis, mastoiditis.
Anatomical defect in CNS – surgery, trauma, congenital
defects.

12. Predisposing factors
1. Age: neonates – highest prevalence d/t
oImmature immune system
oBirth canal
oIncreased permeability to BBB
2. Vaccination: reduces meningitis (Hib)
3. Respiratory infections: alcoholism, diabetes, immunosuppression,
splenectomy, etc.
4. CSF shunts: staphylococcus, pseudomonas, Acinetobacter.
5. Breach in BBB

13. Pathogenesis
Dr.T.V.RaoMD 13
• Susceptibility of bacterial infection on CNS in
the children
–Immaturity of immune systems
• Nonspecific immune
– Insufficient barrier (Blood-brain barrier)
– Insufficient complement activity
– Insufficient chemo taxis of neutrophils
– Insufficient function of monocyte-macrophage system
– Blood levels of diminished interferon (INF) -γand
interleukin -8 ( IL-8 )

14. Pathogenesis
Dr.T.V.RaoMD 14
• Susceptibility of bacterial infection on CNS in the
children
–Specific immune
• Immaturity of both the cellular and Humoral
immune systems
– Insufficient antibody-mediated protection
– Diminished immunologic response
–Bacterial virulence

15. Pathogenesis
Dr.T.V.RaoMD 15
• A offending bacterium from blood invades the
leptomeninges.
Bacterial toxics and Inflammatory mediators are released.
– Bacterial toxics
• Lipopolysaccharide, LPS
• Teichoic acid
• Peptidoglycan
– Inflammatory mediators
• Tumor necrosis factor, TNF
• Interleukin-1, IL-1
• Prostaglandin E2, PGE2
•

16. Pathogenesis
Dr.T.V.RaoMD 16
• Bacterial toxics and inflammatory mediators
cause Suppurative inflammation.
– Inflammatory infiltration
– Vascular permeability alter
– Tissue edema
– Blood-brain barrier destroy
– Thrombosis

17. Pathology
Dr.T.V.RaoMD 17
• Diffuse bacterial infections involve the leptomeninges,
arachnoid membrane and superficial cortical structures,
and brain parenchyma is also inflamed.
Meningeal exudate of varying thickness is found.
There is purulent material around veins and venous
sinuses, over the convexity of the brain, in the depths of
the sulci, within the basal cisterns, and around the
cerebellum, and spinal cord may be encased in pus.
Ventriculitis (purulent material within the ventricles) has
been observed repeatedly in children who have died of
their disease.
•
•
•

18. Pathology
Dr.T.V.RaoMD 18
• Invasion of the ventricular wall with perivascular
collections of purulent material, loss of ependymal
lining, and subependymal gliosis may be noted.
•
•
Subdural empyema may occur.
Hydrocephalus is an common complication of
meningitis.
– Obstructive hydrocephalus
– Communicating hydrocephalus

19. Pathology
Dr.T.V.RaoMD 19
• Blood vessel walls may infiltrated by inflammatory cells.
– Endothelial cell injury
– Vessel stenosis
– Secondary ischemia and infarction
• Ventricle dilatation which ensues may be associated with
necrosis of cerebral tissue due to the inflammatory
process itself or to occlusion of cerebral veins or arteries.

20. Pathology
Dr.T.V.RaoMD 20
• Inflammatory process may result in cerebral edema
and damage of the cerebral cortex.
– Conscious disturbance
– Convulsion
– Motor disturbance
– Sensory disturbance
Meningeal irritation sign is found because the
spinal nerve root is irritated.
Cranial nerve may be damaged
•
•

21. Symptoms of Meningitis and Septicemia
Dr.T.V.RaoMD 21
Meningitis and meningococcal septicemia may
not always be easy to detect, in early stages
the symptoms can be similar to flu. They may
develop over one or two days, but sometimes
develop in a matter of hours
It is important to remember that symptoms
do not appear in any particular order and
some may not appear at all.

22. Clinical manifestation
Dr.T.V.RaoMD 22
• Bacterial meningitis may present acutely (symptoms
evolving rapidly over 1-24 hours) in most cases.
Symptoms and signs of upper respiratory or
gastrointestinal infection are found before several days
when the clinical manifestations of bacterial meningitis
happen.
Some patients may access suddenly with shock and DIC.
•
•

23. Clinical manifestation
23
• Toxic symptom all over the body
– Hyperpyrexia
– Headache
– Photophobia
– Painful eye movement
– Fatigued and weak
– Malaise, myalgia, anorexia,
– Vomiting, diarrhea and abdominal pain
– Cutaneous rash
– Petechiae, purpura

24. Dr.T.V.RaoMD 24

25. Clinical manifestation
Dr.T.V.RaoMD 25
• Clinical manifestation of CNS
– Increased intracranial pressure
• Headache
• Projectile vomiting
• Hypertension
• Bradycardia
• Bulging fontanel
• Cranial sutures diastasis
• Coma
• DE cerebrate rigidity
• Cerebral hernia

26. Clinical manifestation
Dr.T.V.RaoMD 26
• Clinical manifestation of CNS
–Meningeal irritation sign
• Neck stiffness
• Positive Kernig’
s sign
• Positive Brudzinski’
s sign

27. Kernig's sign.
Dr.T.V.RaoMD 27
One of the physically
demonstrable
symptoms of
meningitis is Kernig's
sign. Severe stiffness
of the hamstrings
causes an inability to
straighten the leg
when the hip is
flexed to 90 degrees.

28. Brudzinski's sign
Another physically
demonstrable
symptoms of
meningitis is
Brudzinski's sign.
Severe neck stiffness
causes a patient's
hips and knees to flex
when the neck is
flexed.
Dr.T.V.Rao MD 31

29. Clinical manifestation
Dr.T.V.RaoMD 29
• Clinical manifestation of CNS
–Seizures
• Seizures occur in about 20%-30% of children with
bacterial meningitis.
• Seizures is often found in Haemophilus influenza
and pneumococcal infection.
• Seizures is correlative with the inflammation of
brain parenchyma, cerebral infarction and
electrolyte disturbances.

30. Clinical manifestation
Dr.T.V.RaoMD 30
• Clinical manifestation of CNS
–Conscious disturbance
• Drowsiness
• Clouding of consciousness
• Coma
• Psychiatric symptom
– Irritation
– Dysphoria
– dullness

31. Clinical manifestation
Dr.T.V.RaoMD 31
• Clinical manifestation of CNS
–Meningeal irritation sign
• Neck stiffness
• Positive Kernig’
s sign
• Positive Brudzinski’
s sign

32. Clinical manifestation
Dr.T.V.RaoMD 32
• Clinical manifestation of CNS
– Transient or permanent paralysis of cranial nerves
and limbs may be noted.
– Deafness or disturbances in vestibular function are
relatively common.
– Involvement of the optic nerve, with blindness, is
rare.
– Paralysis of the 6thcranial nerve, usually transient, is
noted frequently early in the course.

33. Clinical manifestation
• Symptom and signs of the infant under the age of 3 months
– In some children, particularly young infants under the age
of 3 months, symptom and signs of meningeal
inflammation may be minimal.
– Fever is generally present, but its absence or hypothermia
in a infant with meningeal inflammation is common.
– Only irritability, restlessness, dullness, vomiting, poor
feeding, cyanosis, dyspnea, jaundice, seizures, shock
and coma may be noted.
– Bulging fontanel may be found, but there is not
meningeal irritation sign.
Dr.T.V.RaoMD 33
•

34. Skin rashes
Dr.T.V.RaoMD 34
•
•
•
•
Is due to small skin bleed
All parts of the body are affected
The rashes do not fade under pressure
Pathogenesis:
a. Septicemia
b. wide spread endothelial damage
c. activation of coagulation
d. thrombosis and platelets aggregation
e. reduction of platelets (consumption )
f. BLEEDING 1.skin rashes
2.adrenal hemorrhage
Adrenal hemorrhage is called Waterhouse-Friderichsen
Syndrome.It cause acute adrenal insufficiency and is uaually
fatal

35. Skin rashes
Dr.T.V.RaoMD 35

36. Dr.T.V.RaoMD 36

37. ‘Glass Test’
Dr.T.V.RaoMD 37
A rash that does not fade
under pressure will still
be visible when the side
of a clear drinking glass is
pressed firmly against the
skin.
If someone is ill or obviously
getting worse, do not
wait for a rash. It may
appear late or not at all.
A fever with a rash that
does not fade under
pressure is a medical
emergency.

38. Complications
Dr.T.V.RaoMD 38
• Subdural effusion
– Subdural effusions occur in about 10%-30% of children with
bacterial meningitis.
– Subdural effusions appear to be more frequent in the
children under the age of 1 year and in Haemophilus
influenza and pneumococcal infection.
– Clinical manifestations are enlargement in head
circumference, bulging fontanel, cranial sutures
diastasis and abnormal trans illumination of the skull.
– Subdural effusions may be diagnosed by the examination of
CT or MRI and subdural pricking.

39. Complication
Dr.T.V.RaoMD 39
• Ependymitis
– Neonate or infant with meningitis
– Gram-negative bacterial infection
– Clinical manifestation
• Persistent hyperpyrexia,
• Frequent convulsion
• Acute respiratory failure
• Bulging fontanel
• Ventriculomegaly (CT)
• Cerebrospinal fluidby ventricular puncture
– WBC>50×109/L
– Glucose<1.6mmol/L
– Protein>o.4g/L

40. Complications
Dr.T.V.RaoMD 40
• Cerebellar hyponatremia
–Syndrem of inappropriate secretion of
antidiuretic hormone (SIADH)
• Hyponatremia
• Degrade of blood osmotic pressure
• Aggravated cerebral edema
• Frequent convulsion
• Aggravated conscious disturbance

41. Complication
Dr.T.V.RaoMD 41
• Hydrocephalus
– Increased intracranial pressure
– Bulging fontanel
– Augmentation of head circumference
– Brain function disorder
• Other complication
– Deafness or blindness
– Epilepsy
– Paralysis
– Mental retardation
– Behavior disorder

42. Meningococcal Meningitis
Dr.T.V.RaoMD 42
• Less common bacterial causes of Meningitis, such as
Staphylococci, enteric bacteria, group B streptococci
and Listeria, occur in sub-populations like the
immunocompromised, neonates, or head trauma
patients.
• Patients with Meningococcal Meningitis present with
sudden onset of fever, intense headache, nausea,
vomiting, stiff neck and, frequently, a petechial rash
with pink macules or, very rarely, vesicles. Delirium
and coma often appear.
• Case fatality rate is between 5% and 15%.

43. Laboratory diagnosis
Specimen collection:
CSF – lumbar puncture in 3 sterile containers
1 - cell count
2 - biochemical analysis
3 bacteriological examination
Blood – culture and sensitivity
Urine – immunochromatographic test

44. Laboratory Findings
Dr.T.V.RaoMD 44
• Peripheral hemogram
–Total WBC count
• 20×109/L ～ 40×109/L WBC
• Decreased WBC count at severe infection
–Leukocyte differential count
• 80% ～ 90% Neutrophils

45. Cytological and biochemical parameters in CSF of normal
individuals and in different types of meningitis
Characteristics Normal individual Pyogenic meningitis Tuberculous meningitis Viral meningitis
CSF pressure
(mm of water) Normal (50–150) Highly elevated (>180) Moderately elevated Slightly elevated/normal
TLC (per mm3 ) 0–5 100–10,000 10–500 25–500
Predominant
cell type Lymphocytes Neutrophils Lymphocytes Lymphocytes
Glucose (mg%) 40–70 < 40 mg/Dl 20-40 absent
Total proteins 15-45 >45 100–500 mg/dL 20–80 mg/dL
( mg%) (moderately increased) (markedly increased) (mild increase)

46. • CSF microscopy ( gram stain):
- Heaped smear
- Centrifugation
• Direct antigen detection:
-From CSF: supernatant- latex agglutination test - S. pneumoniae,
S.agalactiae, N.meningitidis, H.influenza or E.coli
-From urine: ICT – C-polysaccharide antigen of S. pneumoniae.
• Culture: chocolate agar, blood agar and MacConkey agar.

47. Culture and identification properties of common bacterial agents of
pyogenic meningitis
Streptococcus pneumoniae:
• Culture: It produces α-hemolytic colonies on blood agar, described as
draughtsman-shaped or carrom coin appearance
• Biochemical identification: It shows bile soluble, ferments inulin and
sensitive to optochin.
Neisseria meningitidis:
It produces non- hemolytic colonies on blood agar, which on smear shows
gram-negative diplococci.
• Biochemical identification: Meningococci are catalase and oxidase positive.
They ferment glucose and maltose but not sucrose
• Serogrouping: Slide agglutination serogrouping (SASG) test is done to
identify the serogroups of meningococci isolates by using appropriate antisera.
Haemophilus influenzae:
• Culture: Blood agar with S. aureus streak line shows satellitism.
• Biochemical identification: Disk test for X and V factor requirement shows
growth surrounding combined XV disk.

48. Streptococcus agalactiae:
• Culture: It produces β-hemolytic colonies on blood agar, which on smear
shows gram-positive cocci in short chain.
• Biochemical identification: It shows CAMP test positive and resistance to
bacitracin
• Serogrouping with group specific antisera shows Lancefield group B.
Gram-negative bacilli meningitis:
• Escherichia coli and Klebsiella produce lactose-fermenting colonies on
MacConkey agar; identified by ICUT tests
• Non-fermenters: Pseudomonas is oxidase positive, whereas Acinetobacter is
oxidase negative. They produce non-lactose fermenting colonies; identified by
ICUT tests.
Listeria monocytogenes:
• Motility: It shows tumbling type of motility at 25°C but nonmotile at 37°C
(called differential motility, which is due to temperature dependent flagella
expression)
• Culture: It grows on blood agar (β-hemolytic colonies), and chocolate agar.
Note: Selective media such as PALCAM agar (containing mixture of antibiotics)
may be useful for isolation of Listeria from specimens such as food and
environmental samples

49. Laboratory Findings
Dr.T.V.RaoMD 49
• Rout examination of cerebrospinal fluid (CSF)
– Increased pressure of cerebrospinal fluid
– Cloudiness
– Evident Increased total WBC count (>1000×109/L)
– Evident Increased neutrophils in leukocyte differential count
– Evident Decreased glucose (<1.1mmol/l)
– Evident Increased protein level
– Decreased or normal chlorinate
– CSF film preparation or cultivation : positive result

50. Laboratory Findings
Dr.T.V.RaoMD 50
• special examination of CSF
–Specific bacterial antigen test
• Countercurrent immuno-electrophoresis
• Latex agglutination
• Immunoflorescent test
– Neisseria meningitides (meningococcus)
– Haemophilus influenza
– Streptococcus pneumoniae ( pneumococcus)
– Group B streptococcus

51. Laboratory Findings
Dr.T.V.RaoMD 51
• Especial examination of CSF
–Other test of CSF
• LDH
• Lactic acid
• CRP
• TNF and Ig
• Neuron specific enolase (NSE)

52. Differential diagnosis
Dr.T.V.RaoMD 52
• Clinical manifestation of bacterial meningitis is similar to
clinical manifestation of viral, tuberculosis , fungal and
aseptic meningitis.
• Differentiation of these disorders depends upon careful
examination of cerebrospinal fluid obtained by lumbar
puncture and additional immunologic, roentgenographic,
and isotope studies.

53. Antibiotic Therapy
Dr.T.V.RaoMD 53
• Selection of antibiotic
– No Certainly Bacterium
• Community-acquired bacterial infection
• Nosocomial infection acquired in a hospital
• Broad-spectrum antibiotic coverage as noted below
– Children under age 3 months
» Cefotaxime and ampicillin
» Ceftriaxone and ampicillin (children over age 1months)
– Children over 3 months
» Cefotaxime or Ceftriaxone or ampicillin and chloramphenicol

54. Antibiotic Therapy
Dr.T.V.RaoMD 54
• Certainly Bacterium
– Once the pathogen has been identified and the
antibiotic sensitivities determined, the most
appropriate drugs should selected.
• N meningitides : penicillin, - cephalosporin
• S pneumoniae: penicillin, - cephalosporin, Vancomycin
• H influenza: ampicillin, cephalosporin
• S aureus: penicillin, nefcillin, Vancomycin
• E coli: ampicillin, chloramphenicol, - cephalosporin

55. Antibiotic Therapy
Dr.T.V.RaoMD 55
• Course of treatment
– 7 days for meningococcal infection
– 10 ～ 14 days for H influenza or S pneumoniae
infection
– More than 21 days for S aureus or E coli infection
– 14 ～ 21 days for other organisms

56. Treatment
Dr.T.V.RaoMD 56
General and Supportive Measures
• Monitor of vital sign
• Correcting metabolic imbalances
– Supplying sufficient heat quantity
– Correcting hypoglycemia
– Correcting metabolic academia
– Correcting fluids and electrolytes disorder
• Application of cortical hormone
– Lessening inflammatory reaction
– Lessening toxic symptom
– lessening cerebral edema

57. General and Supportive Measures
Dr.T.V.RaoMD 57
• Treatment of hyperpyrexia and seizures
– Pyretolysis by physiotherapy and/or drug
– Convulsive management
• Diazepam
• Phenobarbital
– Subhibernation therapy
Treatment of increased intracranial pressure
– Dehydration therapy
• 20%Mannitol 5ml/kg vi q6h
• Lasix 1-2mg/kg vi
•

58. General and Supportive Measures
Dr.T.V.RaoMD 58
–Treatment of septic shock and DIC
• Volume expansion
• Dopamine
• Corticosteroids
• Heparin
• Fresh frozen plasma
• Platelet transfusions

59. Treatment
Dr.T.V.RaoMD 59
Complication Measures
Subdural effusions
– Subdural pricking
• Draw-off effusions on one side is 20-30ml/time.
• Once daily or every other day is requested.
• Time cell of pricking may be prolonged after 2 weeks.
Ependymitis
– Ventricular puncture — drainage
• Pressure in ventricle be depressed.
• Ventricular puncture may give ventricle an injection of antibiotic.
•
•

60. Complication Measures
Dr.T.V.RaoMD 60
• Hydrocephalus
– Operative treatment
• Adhesiolysis
• By-pass operation of cerebrospinal fluid
• Dilatation of aqueduct
SIADH (Cerebral hyponatremia)
– Restriction of fluid
– supplement of serum sodium
– diuretic
•

61. Prognosis
Dr.T.V.RaoMD 61
• Appropriate antibiotic therapy reduces the
mortality rate for bacterial meningitis in
children, but mortality remain high.
• Overall mortality in the developed countries
ranges between 5% and 30%.
• 50 percent of the survivors have some sequelae
of the disease.

62. Chronic meningitis

63. Definition
• It is characterized by persistence of signs and symptoms as well as the CSF abnormality for
>4 weeks.
Agents of chronic meningitis:
Bacterial agents
Common bacterial agents • Partially treated suppurative meningitis • Parameningeal
infections (e.g. otitis media) • Mycobacterium tuberculosis • Borrelia burgdorferi (Lyme
disease) • Treponema pallidum (secondary, tertiary syphilis)
Rare bacterial agents: Nocardia, Actinomyces, Tropheryma whipplei, Leptospira, Brucella.
Viral agents
Some of the agents of acute viral meningitis may also present as chronic meningitis.
Examples: Mumps, echoviruses, herpesviruses, HIV and lymphocytic choriomeningitis virus.
Parasitic agents
• Toxoplasma gondii • Free-living amoebae • Trypanosoma brucei (African sleeping sickness)
• Angiostrongylus cantonensis (Eosinophilic meningitis) • Gnathostoma spinigerum •
Baylisascaris procyonis • Cysticercosis, schistosomiasis, echinococcal disease • Toxocara canis
and Trichinella.
Fungal agents
• Cryptococcus neoformans • Candida albicans • Blastomyces dermatitidis • Histoplasma
capsulatum • Coccidioides immitis • Aspergillus species • Sporothrix schenckii •
Pseudallescheria boydii • Cladophialophora bantiana

64. Viral meningitis

65. Aseptic Meningitis
• It is the inflammation of subarachnoid space due to viral etiology.
• It is the second most common type of meningitis, next to acute
bacterial meningitis.
• It is often less severe than bacterial meningitis and has a better
prognosis.
• Etiological Agents:
-Enteroviruses (Coxsackie's and echovirus): most common.
-Adenovirus
-Arbovirus
-LCM virus
-Measles virus
-Herpes Simplex Virus
-Varicella
65

66. Viral Meningitis
Dr.T.V.RaoMD 66
Reservoirs:
-Humans for Enteroviruses, Adenovirus, Measles, Herpes Simplex,
and Varicella
-Natural reservoir for arbovirus birds, rodents etc.
Modes of transmission:
-Primarily person to person and arthopod vectors for
arboviruses
Incubation Period:
-Variable. For enteroviruses 3-6 days, for arboviruses 2-
15 days
Treatment:
No specific treatment available.
Most patients recover completely on their own.

67. Non Polio Enteroviruses
Dr.T.V.RaoMD 67
Types:62 different types known:
-23 Coxsackie A viruses,
-6 Coxsackie B viruses,
-28 echoviruses, and 5 other
How common?
-90% of all viral meningitis is caused by Enteroviruses
-Second only to "common cold" viruses, the rhinoviruses.
-Estimated 10-15 million/ more symptomatic infections/yr in US
How does infection spread?
Virus present in the respiratory secretions & stool of a patient.
Direct contact with secretions from an infected person.
Parents, teachers, and child care center workers may also become infected by
contamination of the hands with stool.

68. • Arboviral meningitis
• HIV meningitis
• Mumps meningitis
• LCM meningitis

69. Laboratory criteria for diagnosis:
CSF showing ≥ 5 WBC/cu mm
No evidence of bacterial or fungal meningitis.
Case classification
Confirmed: a clinically compatible illness diagnosed by a physician as
aseptic meningitis, with no laboratory evidence of bacterial or fungal
meningitis
Aseptic meningitis is a syndrome of multiple etiologies, but most cases are
caused by a viral agent

70. Cytological and biochemical parameters in CSF of normal
individuals and in different types of meningitis
Characteristics Normal individual Pyogenic meningitis Tuberculous meningitis Viral meningitis
CSF pressure
(mm of water) Normal (50–150) Highly elevated (>180) Moderately elevated Slightly elevated/normal
TLC (per mm3 ) 0–5 100–10,000 10–500 25–500
Predominant
cell type Lymphocytes Neutrophils Lymphocytes Lymphocytes
Glucose (mg%) 40–70 < 40 mg/Dl 20-40 absent
Total proteins 15-45 >45 100–500 mg/dL 20–80 mg/dL
( mg%) (moderately increased) (markedly increased) (mild increase)

71. Treatment
Treatment of almost all cases of viral meningitis is primarily
symptomatic:
Analgesics, antipyretics, antiemetics and fluid and electrolyte
replacement.
Oral or intravenous acyclovir may be of benefit in patients with
meningitis caused by HSV-1 or 2 and in cases of severe EBV or VZV
infection.
Patients with HIV meningitis should receive highly active antiretroviral
therapy.

72. Parasitic infections of central nervous system
Protozoan infections of CNS
• Free-living amoebae infections of CNS*
• Toxoplasma encephalitis*
• Cerebral malaria (Plasmodium falciparum)*
• African sleeping sickness (Trypanosoma brucei)*
• Chagas’ disease (meningoencephalitis, Trypanosoma cruzi)
• Cerebral amoebiasis (E. histolytica)
Cestode infections of CNS
• Neurocysticercosis (Taenia solium)*
• Others: Taenia multiceps, Spirometra and Echinococcus
Trematode infections of CNS
• Schistosoma mansoni and S. japonicum infections
• Cerebral paragonimiasis
Nematode infections of CNS
• Hyperstrongyloidiasis syndrome (Strongyloides)
• Eosinophilic meningitis (Angiostrongylus cantonensis)
• Others: Loa loa (meningoencephalitis), Trichinella spiralis, Toxocara, Baylisascaris procyonis and
Gnathostoma infections

73. Fungal agents causing CNS infections
Primary CNS pathogen: Cryptococcus neoformans
Fungi which primarily cause infections of other body sites, rarely
cause CNS infections
• Agents of systemic mycoses: Blastomyces dermatitidis, Histoplasma
capsulatum and Coccidioides immitis
• Agents of subcutaneous mycoses: Sporothrix schenckii,
Pseudallescheria boydii and Cladophialophora bantiana
• Opportunistic fungal agents : Candida albicans, Aspergillus species
and Mucor (rhinocereberal mucromycosis)
• Others: Microsporidia

74. Cryptococcal meningitis

75. Cryptococcal meningitis
Cryptococcal meningitis is caused by a capsulated yeast called
Cryptococcus neoformans, which is capable of producing potentially
fatal meningitis in HIV infected people.
C.Neoformans
C.Gattii

76. Pathogenesis and Virulence factors
• Infection is acquired by inhalation of aerosolized forms of
Cryptococcus.
• Polysaccharide capsule—It is the principal virulence factor of the
fungus. It is antiphagocytic and also inhibits the host’s local immune
responses
• Ability to make melanin by producing an enzyme called phenyl
oxidase
• Production of other enzymes such as phospholipase and urease.
• CNS spread: The unique feature of Cryptococcus is its ability to
cross blood-brain barrier which occurs by the yeast cells either they
migrate directly across the endothelium or carried inside the
macrophages as “Trojan horse”

77. Lab diagnosis
• Specimens: CSF, blood or skin scrapings.
• Direct Detection Methods
1. Negative staining: Modified India ink stain (added with 2%
mercurochrome) and nigrosin stain - demonstrate the capsule -
refractile delineated clear space surrounding the round budding
yeast cells against black background.
2. Gram staining may show gram-positive round budding yeast cells.
3. Other stains include:
Mucicarmine stain: It stains the carminophilic cell wall of C.
neoformans Masson-Fontana stain: It demonstrates the production of
melanin
Alcian blue stain: To demonstrate the capsule.
4. Antigen detection: The capsular antigens can be detected from
CSF or serum by latex agglutination test. It is a rapid and sensitive
(95% sensitivity) and specific method.

78. CULTURE
Negative staining SDA agar

79. Confirmation of Cryptococcus species is made by:
Niger seed agar and bird seed agar: They are used to demonstrate
melanin production (brown colored colonies).
Growth at 37°C .
Urease test is positive
Assimilation of inositol and nitrate
Mouse pathogenicity test
Automated identification system such as MALDI-TOF

80. TREATMENT
• Treatment depends upon the type of cryptococcosis.
• Cryptococcosis without CNS involvement: Fluconazole is the drug of
choice
• HIV-infected patients with CNS involvement: The recommended
regimen is induction phase for two weeks (amphotericin B ±
flucytosine) followed by oral fluconazole therapy till CD4 T cell count
raises >200 /µL for 6 months.