CNS infections ppt

1. Infection of Central Nervous
System
Tanja Jovanovic

2. Infections of CNS
• Numerous infectious agents ( more than
50 species) affect the nervous system
• Meningitis – inflamation of meninges
• Encephalitis- inflamation of the
parenchyma of brain
• Meningoencephalitis – inflamation of brain
and meninges

3. Portals of Infection of the Central
Nervous System
• Pathogens may access the CNS through breaks in the bones and
meninges, through medical procedures such as spinal taps, or by
traveling via axonal transport in peripheral neurons to the CNS.
Microbes carried in the blood or lymph may penetrate the blood-brain
barrier by infecting and killing cells of the meninges.
• Some pathogens gain access to the CNS when localized inflammation
distorts the cells of the blood-brain barrier, changing its permeability;
such change is more likely during chronic infection by many pathogens.
Circulation of cerebrospinal fluid can carry infective microbes throughout
the cranial cavity and spinal column.

4. Meningitis
• Bacterial meningitis is defined as
meningitis with evidence of pathogenic
bacteria in the CSF
• Aseptic meningitis is defined as meningitis
without the usual evidence of pathogenic
bacteria in the CNS

5. Bacterial Diseases
of the Nervous System
• Bacteria can infect cells of the nervous system,
but also toxin released by bacteria growing
elsewhere in the body can also affect neurons.
• eg. botulism and tetanus involve toxins.
However, the most common bacterial infection
of the nervous system is bacterial meningitis

6. Etiology
• More than 80% of cases of bacterial meningitis
are encapsulated and have high affinity for
specific receptors in the choroid plexus or the
meninges
• S. Pneumoniae
• N. Meningitidis (serotypes A,B,C and Y)
• H. Influenzae (type b)
• The remaining 20% of cases are caused by L.
Monocytogenes, S. Aureus, S. Epidermidis and
M. tuberculosis

7. Meningitis
Bacterias Neisseria meningitidis (~20%)
Streptococcus pneumoniae (~30%)
Haemophilus influenzae b
Enterobacteriaceae
Mycobacterium tuberculosis
Leptospira interrogans
Listeria monocytogenes
Neonatal infection E. coli
Steptokoke grupe B
Microscopy(CSF), isolation-
cultures (CSF), detection of
antigen
Viruses Enterovirusi
HSV
Virus mumpsa
Togavirusi
Bunyavirusi
Arenavirusi
LCMV
Isolation of viruses
PCR
Fungi Cryptococcus neoformans, Coccidioides
immitis
Candida spp.
Histoplasma capsulatum
Blastomyces dermatitidis
Microscopic examination of an
indian ink preparation

8. Signs and Symptoms
Bacterial meningitis is characterized by an increased number of
white blood cells in the CSF, sudden high fever, and by intense
meningeal inflammation, which accounts for most of the signs
and symptoms: Swelling of the meninges retards the normal
flow of CSF, putting pressure on the underlying organs.
Inflammation of the cranial meninges typically produces severe
headache, nausea, vomiting, pain, and in many cases loss of
various brain functions. Inflammation of the spinal meninges
puts pressure on surrounding nerves and muscles,producing
stiffness in the neck and affecting sensory input and muscular
control. When the brain becomes infected—a condition called
encephalitis—deafness, blindness, drastic changes in the
patient’s behavior, coma, or death may result.

9. Epidemiology of bacteria meningitis - 1
• Age dependence
Neonatal meningitis (E coli, Streptococcus
group B, Klebsiella species, L.
Monocytogenes)
Meningitis in older children, adolescent and
adults ( N. Meningitidis, S. Pneumoniae)
Meningitis in elderly ( S. Pneumoniae)

10. Epidemiology of bacteria meningitis - 1
• Bacterial factors
Polysaccharide capsules (resist to phagocytosis and poorly
immunogenic in children younger that 2 years)
Host factors
1.Gendred (more prevalent in men)
2.Prematurity,prolonged or difficult delivery or maternal
infection, conginital immunodeficienes
3.Age (from birth to 5 years of age)
4. Acquired immunodeficiences
5. Poor sanitation, lack of access to preventive care

11. Pathogenesis of bacterial meningitis
• 1.Bacterial access to meninges by
a) Bacteremic spread
b) Direct invasion
2. Release of bacterial products

12. • Bacterial meningitis is also typified by a dramatic
increase in the number of leukocytes in the CSF.
Aspinal tap reveals the normally clear CSF is
quite milky in color due to the large number of
bacteria and white blood cells. Petechiae -
small, dark purplish hemorrhages of blood
vessels in the skin—aresometimes present.

13. Diagnosis of bacterial meningitis
• Lumbal puncture
CSF findings
- White blood cell count is eleveted, with the
predominance of neutrophils
- Glucose level are low
- Protein level are high
- Cultures

14. • Neisseria meningitidis is one of only two
species of Gram-negative cocci that
regularly causes disease in humans.
Researchers have identified13 antigenic
strains; strains A, B, C, and W135 cause
most cases of disease in humans.

15. • Meningococci have fimbriae and polysaccharide capsules,
• as well as a major cell wall antigen called lipooligosaccharide
LOS), composed of lipid A (endotoxin) and sugar molecules—
all of which enable the bacteria to attach to human cells. Cells
of Neisseria that lack any of these threestructural features are
avirulent.
• The polysaccharide capsules also resist lytic enzymes of the
body’s phagocytes, allowing phagocytized meningococci to
survive, reproduce, and be carried throughout the body within
neutrophils and macrophages.
• Much of the damage caused by N. meningitidis results from
blebbing—a process in which the bacterium sheds extrusions of
its outer membrane. The lipid A component of LOS thereby
releasedinto the body triggers fever, vasodilation, inflammation,
shock, and widespread blood clotting.

16. Streptococcus pneumoniae
• The cells of all virulent strains of S. pneumoniae
are surrounded by a polysaccharide capsule,
which protects them from digestion after
phagocytosis. Unencapsulated strains do not
cause disease.Pathogenic pneumococci also
produce secretory IgA protease,which destroys
immunoglobulin A secreted against the
bacteria,and pneumolysin, which suppresses
the digestion of phagocytized bacteria by
interfering with the action of lysosomes.

17. Haemophilus influenzae
• Most strains of H. influenzae have
polysaccharide capsules that resist
phagocytosis. Researchers distinguish
among six strains of Haemophilus by
differences in capsular antigens. Before
the introduction of an effective vaccine in
the 1990s, 95% of H. influenzae diseases
in the United States were caused by type
b

18. Streptococcus agalactiae
• is a normal member of the vaginal
microbiota in about a third of women. It
produces a protective capsule that allows
it to evade phagocytosis when it gets into
the blood. This bacterium causes
bacteremia, pneumonia, and meningitis in
newborns.

19. Listeria monocytogenes
• found in soil, water, mammals, birds, fish,
and insects. It enters the body in
contaminated food or drink. Listeria rarely
pathogenic in healthy adults, who
experience either no symptoms or only a
mild, flulike illness. In contrast, infection in
pregnant women, fetuses, newborns, the
elderly, and immunocompromisedpatients
(particularly those with suppressed
• T cell immunity) can result in meningitis

20. Listeria monocytogenes
• Inside the cell’s phagosome, Listeria
synthesizes listeriolysinO,an enzyme that
breaks open the phagosome before a
lysosomecan fuse with it; thus, Listeria avoids
digestion by the cell. Listeria then grows and
reproduces in the cell’s cytosol, sheltered from
the B cell immune system.
• Listeria continues to avoid exposure to the
immune system via a unique method of
transferring itself to neighboring cells without
having to leave host cells

21. Listeria monocytogenes
• The pathogen polymerizes a host cell’s actin
molecules to form stiff actin filaments that lengthen
and push the bacterium through cytosol to the cell’s
surface, where it forms a pseudopod. A neighboring
macrophage or epithelial cell then endocytizes the
pseudopod, and Listeria once again escapes from
the phagosome to continue its intracellular
parasiticexistence within a new host cell. The
bacterium produces no toxins or other enzymes that
add to its virulence

22. a. Streptococcus pneumoniae (G+)
b. Neisseria meningitidis (G-)
c. Lysteria monocytogenes (G+)
a. b.
c.

23. Botulism
• Botulism is not an infection, but
instead an intoxication (poisoning)
caused by a toxin of Clostridium
botulinumthat adversely affects synapses
of the peripheral nervous system. Botulism
toxin is one of the more powerful natural
poisons

24. • When a nerve impulse arrives at the terminus of a
motor neuron, ACh vesicles fuse with the neuron’s
cytoplasmic membrane,releasing ACh into the
synaptic cleft. Molecules of Ach then diffuse across
the cleft and bind to receptors on the cytoplasmic
membrane of the muscle cell. The binding of ACh to
the ACh receptor triggers a series of events inside the
muscle cell that results in muscle contraction.
• Botulism toxins act by binding irreversibly to
neuronal cytoplasmic membranes, thereby
preventing the fusion of vesicles and the
secretion of acetylcholine into the synaptic cleft

25. C tetani
• Cells of C. tetani release a potent neurotoxin
called tetanospasmin Tetanospasmin is
composed of two polypeptides held together by
a disulfide bond. C. tetani remains localized at
the site of infection;only the toxin moves to the
central nervous system. Tetanospasmin blocks
the release of inhibitory neurotransmitter.
• With inhibition blocked, excitation of the motor
neurons is unregulated, and the muscle is
signaled to contract.The result is that muscles
contract and do not relax

26. Diagnosis of Cryptococcus neoformans
meningitis
Cryptococcus neoformans
(blastospore with capsula)

27. Encephalitis /encephalomyelitis
Rickettsia spp.
Brucella spp.
Borrelia burgdorferi
Leptospira interrogans
Treponema pallidum
Lysteria monocytogenes
Mycobacterium tuberculosis
Serology
Serology, PCR; isolation
Serology, isolation,
Direct microscopy(CSF), isolation (CSF, blood)
Direct microscopy(CSTF), PCR
Viruses HSV
Morbilli virus
EBV
HIV
VZV
CMV
Mumps virus
Enteroviruses
Togaviruses
Bunyaviruses
Arenaviruses
rabies virus
Other arboviruses
Serology
PCR and isolation (biopses)
+isolation form nasopharingeal asp.
+ isolation from feces
Serology
DIF

28. Encefalitis /Encefalomijelitis (encephalitis /encephalomyelitis)
Fungi Cryptococcus neoformans
Aspergillus spp.
Zigomicete
Direct microscopy(CSF), isolation (CSF, blood);
Ag detection (CSF); serology
Protozoe Naegleria fowleri
Acanthamoeba spp.
Toxoplasma gondii
Trypanosoma gambiense et
rhodesiense
Plasmodium falciparum
Direct microscopy(CSF), isolation (CSF, blood);
Ag detection (CSF); serology
Serology, direct microscopy, isolation, PCR
(CSF)
Direct microscopy
Serology
Helmintes Taenia solium (cysticercosis)
Echinococcus granulosus
Echinococcus multilocularis
Toxocara canis
Serology
Apsces
Epidural apsces
Subdural empijem
Streptococcus milleri
Gram- anaerobne bakterije
Enterobakterije
Staphylococcus aureus
Zigomicete, Aspergillus spp.,
Candida spp.
Toxoplasma gondii

31. Conjunctivitis /Keratitis
Bacterias Neisseria spp.
Streptococcus spp.
Staphylococcus aureus
Haemophilus spp.
Enterobakterije
Pseudomonas spp.
Mycobacterium spp.
Moraxella lacunata
Chlamydia trachomatis
Direct microscopy
Smear (Giemsa) –DIF
Viruses Adenovirusi
Enterovirusi
Virus influenze
Morbilli virus
Isolation
PCR
Fungi Candida spp.
Sporothrix schenckii
Microscopy
Protozoa, Helminties Acantamoeba, Onchocerca
volvulus
Loa loa
Detection of microfilarias
serology
Detection of microfilarias in
blood; serology

32. Which bacteria is most prevalent as a normal microflora of
conjunctiva?
• Staphylococcus epidermidis
Which bacteria induced blindness as a consequence of neonatal
infection?
• Chlamydia trachomatis
• Neisseria gonorrhoeae
Which disease is indeced by Haemophilus influenzae biotyp
aegyptius? In what population is prevalent?
• Epidemic purulent conjunctivitis
What is hordeolum?Which bacteria induced chordeolum?
• Infection of Meibomian glands
• Staphylococcus aureus

33. • Adenoviruses are a common cause of
conjunctivitis. In older children the conjuctivitis
can be associated with pharyngitis
Rubella virus – congenital cataract
Keratitis is the most comon cause of corneal
blindness, induced by HSV1/2

34. Infection of ear
Otitis
externa
Pseudomonas aeruginosa
Staphylococcus aureus
Streptococcus pyogenes
Aspergillus spp.
Candida spp.
Otitis
media
Streptococcus pneumoniae
Haemophilus influenzae
Streptococcus pyogenes
Staphylococcus aureus
Moraxella catarrhalis (deca)
Respiratorni virusi

35. The most frequent etiological agents of
otitis media (above 2 years of age)
Streptococcus pneumoniae
• Haemophilus influenzae
• Moraxella catarrhalis
Moraxella - infections?
• Otitis media
• Sinusitis
• Blefarits
• Bronhitis
• Pneumonia