this ppt mentions meningitis, encephalitis, and abscesses

1. Infections of the Central Nervous System (CNS)

2. Contents
• Anatomy of CNS
• Cerebrospinal Fluid Characteristics
• Host-Pathogen Relationships
• Epidemiology and vaccine
• Bacterial Meningitis
• Brain Abscesses
• Pathogenesis
• Encephalitis
• Diagnosis
• Toxins

5. Introduction
Infections of the central nervous system (CNS) are serious and
potentially life-threatening. These infections may be caused by
bacteria, viruses, fungi, toxin, prion or parasites.
 The physician arrives at a hypothetical diagnosis
based on the patient’s age, clinical presentation,
physical examination, local epidemiology of CNS
infections, Cerebrospinal fluid (CSF) analysis, and
often radiologic studies. The specific causative
diagnosis is arrived at by laboratory testing.

6. Anatomy of C.N.S
• The CNS encompasses:
1. The Brain .
2. Spinal Cord.
3. Cranial Nerves.
But not the peripheral
nerves.
Nerves System

7. Antinomy of Meninges
The brain and spinal cord are protected by the skull and vertebral column
respectively,
and three layers of meninges:
1. The Dura
2. Arachnoid
3. Pia Mater
The subarachnoid space between the arachnoid and pia mater is occupied by surface blood vessels and CSF.

8. Cerebrospinal Fluid Characteristics- Adult
Cerebrospinal fluid is a clear, colorless, and sterile fluid.
In normal adults:
1. The CSF Volume Ranges From 90 To 150 Ml.
2. The Protein Level Is 15 To 45 Mg/Dl.
3. The Csf Glucose Level Is 40 To 80 Mg/Dl.
4. Leukocytes 0 To 7 /µl.
5. Differential Count Of 60% To 80% Lymphocyte.
6. Neutrophils 0% To 15%
7. Monocytes 10% To 40%
CSF serves five
primary purposes:
buoyancy, protection,
chemical stability,
waste removal, and
prevention of brain
ischemia.

9. Cerebrospinal Fluid-Newborns
In Newborns:
Compared with adults, normal newborns have higher CSF
concentrations of
1. Protein (15 To150 Mg/Dl)
2. Glucose (30 To 120 Mg/Dl)
3. Cells (0 To 30 Leukocytes/Ml)
4. With A Greater Percentage Of Monocytes And Neutrophils.

10. Cerebrospinal Fluid
• The rarity of leukocytes and protein (including
immunoglobulins) in the 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.

11. Host-Pathogen Relationships
Host risk factors that predispose to infection include:
Extremes Of Age
Nutritional And Immunologic Status,
Comorbidities, Such As Alcoholism, Diabetes Mellitus, Malignancy, Renal Failure, Head Trauma, And
Neurosurgical Procedures.
 Structural components of the organism such as surface encapsulation and fimbriae that
mediate adherence to respiratory tract epithelial cells play an important role in
meningeal infection.
 Additionally, the bacterial capsule can resist neutrophil phagocytosis and complement-
mediated bactericidal activity, thus enhancing survival in the bloodstream.
 Host factors that attempt to limit infection include the presence of mucosal immunity
mediated via (IgA), complement activation, and the presence of organism-specific
antibodies.

13. Epidemiology
• The epidemiology of bacterial meningitis has changed over the decades.
• Since the introduction of vaccination against Haemophiles influenzae type b in
the 1980s there has been a dramatic reduction in the incidence of meningitis
caused by this organism.
• With the inclusion of pneumococcal vaccination in the routine immunization
schedule for children,
• Universal screening of pregnant women for group B streptococcus (GBS) and
• availability Of newer meningococcal vaccines there has been a further
reduction in the incidence of bacterial meningitis.

14. • Meningitis. In the United States, about 4100 cases of bacterial meningitis
including 500 deaths, occurred each year from 2003 to 2007 The mortality rate
ranges from less than 5% for H. influenzae meningitis to about 10% for
meningococcal meningitis and about 20% for those with pneumococcal
meningitis.
• The incidence of meningococcal meningitis Is Higher In sub-Saharan Africa (the
so-called meningitis belt) extending from Senegal in the west to Ethiopia in the
east.
• Although mortality rates have decreased as a result of improved medical
management of CNS infections, some children may suffer developmental delay
and develop learning disabilities and behavioral problems. Thus, infections of
the CNS are a cause of immediate and long-term health concerns.

15. Meningitis
Acute meningitis is commonly caused by bacteria (e.g., Streptococcus
pneumoniae, Neisseria, meningitidis, H.influenzae, Listeria monocytogenes).
Less commonly, it is caused by other organisms, such as spirochetes (e.g.,
Treponema pallidum, Borrelia burgdorferi).
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.

16. Bacterial Meningitis
The likely causative agents of bacterial meningitis depend on:
1. the age of the patient .
2. host factors such as immune status.
3. presence of a cerebrospinal leak.
4. presence of a foreign body,
such as a ventriculoperitoneal shunt.

17. 1.The Age Of
The Patient

18. Pathogenesis
Ways of infection:
1. Direct invasion ( from sinuses or mastoid).
2. Blood stream.
3. Neurological procedure.
4. Colonization respiratory tract (then enters Blood stream)(most common).

19. Pathogenesis
• The exact mechanism whereby bacteria gain access to the CNS or the
exact site of entry into the CNS remains unclear.
• In the subarachnoid space, bacteria replicate, release bacterial
components, and cause an inflammatory reaction.

20. 1. Streptococcus pneumoniae
• A gram-positive diplococcus, is the most common cause of meningitis in adults
and in children.
• Of more than 90 serotypes, only a few serotypes- including 4,6B, 9V, 14, 18C, 19F
and 23 F- accounted for most cases of invasive childhood pneumococcal
infections in US before the implementation of routine immunization in infants
with the heptavalent conjugate vaccine (PCV7).
• Serotype 19A has emerged as the most common cause on invasive disease and
the serotype most associated with resistance in PCV7-Immunized children.
• Patients with Sickle cell anemia those splenectomy or asplenia, malignancy,
malnutrition, and chronic renal or liver disease are more likely to develop serious
pneumococcal disease.

21. Three pneumococcal vaccines are available for use:
1. The heptavalent pneumococcal conjugate vaccine (PCV 7)
2. The13-valent pneumococcal conjugate vaccine (PCV13), which is composed of
purified polysaccharides of 13 serotypes conjugated to a diphtheria protein
3. The 23-valent vaccine (PS23), composed of 23 purified capsular
polysaccharides
 The PCV-13 pneumococcal conjugate vaccine is currently part of the routine
immunization schedule of children.
Vaccines

22. Pneumococcal conjugate vaccine (PCV)
The polysaccharide capsule produce
a prominent halo around organisms

23. 2. Hemophilus influenzae
• Hemophilus influenzae type b (Hib), a gram-negative coccobacillus.
• Hib is an encapsulated strain of bacteria that colonizes the human nose and throat. The
bacteria may spread throughout the body through the bloodstream and may become
life-threatening.
• Is an important cause of bacterial meningitis in children. In addition to meningitis, it
can cause otitis media, pneumonia, and epiglottitis.
• H. influenzae was previously the most common cause of bacterial meningitis, especially
in young children.
• Most cases were caused by the capsular type b strains.
• 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.

26. 3. Neisseria meningitidis
• Neisseria meningitidis, a gram-negative diplococcus, is classified into 12 serogroups based
on antigenically distinct, non–cross-reactive capsular polysaccharides.
• Serogroups A, B, C, Y, and W135 account for most cases of meningococcal Disease
Throughout The world.
• Serogroups B, C, and Y account for most cases in Europe and the US.
• Disease attributable to serogroup A is seen in Asia and Africa
• Disease caused by serogroups A and C can occur in epidemics. Outbreaks have also been
reported with the W135 serogroup.

27. Individuals deficient in terminal
components
of complement (C5-9) or
properdin
are at a higher risk for
meningococcal infections.
Incidence of meningococcal infection
according to age.
Petechial rash and neck extension
characteristic of meningococcal meningitis.

28. Vaccines
• Vaccine containing polysaccharides A, C, Y, and W135 is available for use in
individuals older than 2 years.
• A quadrivalent Meningococcal diphtheria conjugate vaccine is approved for
use in adolescents and in those 2 to 55 years of age at high risk for
meningococcal disease.
• A combination vaccine for infants and children ages 6 weeks through 18 months
for the prevention of invasive disease caused by N. meningitidis serogroups C
and Y and H. influenzae type b was recently approved.

29. 4. Listeria monocytogenes
• Listeria monocytogenes is a gram-positive rod.
• Infection by this organism is usually seen in pregnant women, neonates, older
adults, people with alcoholism, and person 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:
1. low CSF leukocyte counts.
2. with a predominance Of lymphocytes.

30. 5. Streptococcus agalactiae
• 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% ).

31. • Approximately 50% of survivors of early-or late-onset meningitis have
long-term neurologic sequalae.
• 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 older than 60 years,
diabetes mellitus, and underlying malignancy.

32. 6. Aerobic gram-negative bacilli
A. Escherichia coli
B. Klebsiella spp
C. Acinetobacter baumannii
D. Pseudomonas aeruginosa
E. Serratia spp
F. Salmonella spp
 These group of bacteria also can 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.

33. Other Bacteria.
• Meningitis caused by Staphylococcus aureus, coagulase-negative staphylococci, or
Abiotrophia and Granulicatella spp. usually occur 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. are
uncommon and are usually associated with a concurrent brain abscess or a contiguous focus
of infection.

34. 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 CSF space and
the distal end is in the peritoneal, pleural, or vascular
space.
• Patients with shunts in place 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.

35. 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.

36. Mycobacterial Infections
• 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 extrapulmonary sites occurs via blood.
• The most common mycobacterial infection of the CNS is tuberculous meningitis
caused by Mycobacterium tuberculosis.
• Other mycobacteria associated with CNS infections include Mycobacterium
bovis, Mycobacterium avium, Mycobacterium intracellulare, Mycobacterium
kansasii, Mycobacterium fortuitum, Mycobacterium abscessus, and
Mycobacterium africanus.

37. HIV infection is a risk factor for tuberculous meningitis.
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.

38. Spirochetal Infections
• The two spirochetes associated with CNS
infection are T. pallidum and B.
burgdorferi. T. pallidum, the causative
agent of syphilis, enters the nervous
system during early infection and can be
isolated from CSF in patients with
primary syphilis.

39. Chronic Meningitis
• Slow-growing organisms (such as Mycobacterium tuberculosis)
that invade the membranes and fluid surrounding your brain
cause chronic meningitis. Chronic meningitis develops over two
weeks or more. The signs and symptoms of chronic meningitis
— headache, fever, vomiting and mental cloudiness — are
similar to those of acute meningitis.

40. Meningoencephalitis and Encephalitis
• Encephalitis is inflammation of the brain.
• Meningoencephalitis also known as encephalomeningitis is an
inflammation of the brain and its surrounding protective membranes.

42. Brain Abscesses
In contrast to the superficial meningeal inflammation seen in meningitis, brain
abscesses are circumscribed areas of tissue destruction containing organisms and
inflammatory cells.
A cerebral abscess(Brain Abscesses) begins as a focal area of acute inflammation,
followed by the development of a necrotic center and the presence of
macrophages and fibroblasts in the periphery.
Eventually there is a diminution in the necrotic center and formation of a
collagenous capsule.
Most cerebral abscesses occur as a result of spread from a contiguous focus of
infection in the middle ear, mastoid cells, or paranasal sinuses.
Brain abscesses secondary to ear infections are usually localized in the temporal
lobe or cerebellum, and those attributable to spread from paranasal sinuses or
from dental infections are seen in the frontal lobe.

43. • The second common mechanism for development of brain abscess is by
hematogenous spread from a distant focus of infection, such as lung abscess,
bronchiectasis, empyema, infective endocarditis, and intraabdominal infections.
• Brain abscesses can also develop secondary to trauma with dural breach or
following neurosurgery.
• In some patients, none of these pathogenic mechanisms is evident.
• The microorganism isolated from brain abscess often depends on the
predisposing condition.
Brain Abscesses

44. • In patients with brain abscess secondary to ear or sinus infection, the common
organisms include streptococci, Bacteroides spp., and Prevotella spp., whereas
in patients with penetrating trauma or infective endocarditis, S. aureus is more
likely to be identified.
• Neutropenic or transplant patients are more susceptible to developing
infections by fungi such as Aspergillus or Mucorales spp.; patients with HIV are
more likely to have infection from T. gondii, Nocardia spp., or Mycobacterium
spp.
Brain Abscesses

46. Laboratory Diagnosis
• The diagnosis of CNS infections is based on examination of CSF
samples obtained by lumbar puncture.
1. Blood cultures are often helpful in identifying the causative
microorganism. Sheep blood and chocolate agar is usually
used for bacterial culture of CSF.
2. Latex agglutination tests for the detection of H. influenzae
type b, S. pneumoniae, group B streptococci, and N.
meningitidis are available
3. multiplex PCR assay.

49. Questions?
• There are normal flora in C.N.S ?
• Acute vs Chronic meningitis ?
• How is cerebrospinal fluid (CSF) produced and distributed in the
central nervous system?
• What is difference among Meningoencephalitis, Encephalitis and
meningitis ?

50. Sources
1. Diagnostic microbiology- Chapter-35
2. Microbiology a systems approach-Chapter 19
3. WHO | Pneumococcal disease
4. Haemophilus influenzae type b Information |
Hib Disease (merckvaccines.com)