Therefore, the CNS is an arsenic environment-it has no normal microbiota. 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 in the CNS.

1. CNS…
 No openings allow microbial colonization of
the central nervous system;
 Therefore, the CNS is an axenic
environment-it has no normal microbiota.
◦ 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.

2. CNS…
 Microbes carried in the blood or lymph may
penetrate the blood-brain barrier by infecting and
killing cells of the meninges, causing meningitis.
 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.

3. Bacterial Diseases of the Nervous
System
 Not only can bacteria infect cells of the nervous system,
 But toxins released by bacteria growing elsewhere in the
body can also affect neurons.
 In the following sections, we consider diseases of both
types-leprosy, which is a disease of cells of the PNS,
 botulism
 tetanus,
 which involve toxins. However, the most common bacterial
infection of the nervous system is bacterial meningitis, which
we consider next

4. CNS…
 Bacterial meningitis involves inflammatory bacterial
infection of the meninges, commonly the pia mater
and arachnoid mater and more rarely the dura mater.

5. CNS…
1. Neisseria meningitidis
 Neisseria meningitidis is one of only two species of
Gram-negative cocci that regularly causes disease in
humans.
 13 antigenic strains; strains A, B, C, and W135 cause
most cases of disease in humans.
 The cells of all strains of Neisseria are nonmotile and
are typically arranged as diplococci (pairs) with their
common sides flattened in a manner reminiscent of
coffee beans

6. Neisseria meningitidis
 The bacterium is known as the meningococcus and its
disease as meningococcal meningitis.
• Pathogenesis and clinical findings
– Aspiration of infective bacteria
– Attach to epithelial cells of nasopharyngeal and
oropharyngeal mucosa
– Cross the mucosal barrier & enter the bloodstream
– May enter the CNS and cause meningitis.
– Meningococcal LPS is responsible for the toxic
effects found in meningococcal disease
– Also antiphagocytic polysaccharide capsule play a
role in the pathogenesis

7. Neisseria meningitidis
• Manifestations of meningococcal infections
• Fulminant Meningococcemia (Purpura Fulminans)
– The most severe form of meningococcemia is the life-
threatening Waterhouse-Friderichsen Syndrome.
– Characterized by high fever, shock, wide spread purpura,
disseminated intravascular coagulation, and adrenal
insufficiency

8. Neisseria meningitidis
– Meningococci shed LOS which stimulate
• monocytes, neutrophils, and endothelial cells,
release cytokines and other mediators
• In addition, meningococci invade the vascular
endothelium, produces molecules that can be
procoagulant as well as adhesive for leukocytes.

9. Neisseria meningitidis
• Fulminant meningococcemia:
– Occurs in 5 to 15% of patients
– begins abruptly with sudden high fever, chills,
myalgias, weakness, nausea, vomiting, and
headache.
– typically, no signs of meningitis
– Pulmonary insufficiency develops within a few
hours
– and patients many die within 24 hours even
with appropriate antibiotic therapy and
intensive care.

10. Neisseria meningitidis
Petechial rash and neck extension characteristic of
meningococcal meningitis.

11. Neisseria meningitidis
• Meningococcal meningitis
– the meninges are inflamed, with thrombosis of
blood vessels
– after an Ip of 1-3 days,
• the onset of meningococcal meningitis is
sudden with a sore throat, headache, &
drowsiness
• and signs of meningitis which include fever,
irritability, stiff neck , photophobia and an
increased level of PMNs in spinal fluid

12. Neisseria meningitidis
• Diagnostic Laboratory Tests
– Specimens: blood for culture, and CSF for smear
and culture
– Culture: CSF specimens are plated on
• "chocolate" agar and incubated at 37 °C in an
atmosphere of 5% CO2
• A modified Thayer-Martin medium with
antibiotics (vancomycin, colistin, amphotericin)
– oxidase +ve: a key test for identifying Neisseriae
– Serology: antibodies to polysaccharides can be
measured by latex agglutination

13. • Epidemiology, Prevention, & Control
 Humans only natural hosts
 Person-to-person transmission by aerosolization
of respiratory tract secretions in crowded
conditions
 Close contact with infectious person (e.g., family
members, day care centers, military barracks,
prisons, and other institutional settings)
 Highest incidence in children younger than 5
years and particularly those younger than 1 year
of age
 5% to 30% Commonly colonize nasopharynx of
healthy individuals
 Vaccine for groups A, C, Y, and W-135 are the
capsular polysaccharides

14. • Treatment
–Penicillin G is the drug of choice
–Either chloramphenicol or a third-
generation cephalosporin is used in
persons allergic to penicillins

15. 2. Streptococcus pneumoniae
 Streptococcus pneumoniae Louis Pasteur discovered
Streptococcus pneumoniae
 “Diplococcus.” Ninety-two different strains of S.
pneumoniae, collectively called pneumococci, are
known to infect humans as normal members of the
microbiota of the throat that opportunistically grow in
the lungs, sinuses, and middle ear and from those
locations move into the meninges via the blood.
 Streptococcus pneumoniae is the leading cause of
meningitis in adults.

16. Streptococcus pneumoniae
 About 40 – 70% of healthy adults are carriers
 Infections usually arise from normal flora (endogenous)

17. Virulence factors
Capsule
– Major determinant of virulence
– Anti-phagocytosis by preventing C3b
complement deposition on the surface
Cell Wall
– Stimulate leukocytes for production of cytokines
– Teichoic acid enhances inflammatory activity

18. Pneumococcal surface protein A, PspA (Choline
binding protein A, CBpA)
• Surface – exposed protein
– Adherence to host tissue, colonization
• prevent the deposition of C3b on the cell surface
• binds to lactoferrin, may be involved in iron
acquisition

19. • Autolysin. breaks the peptide cross-linking of
the cell wall peptidoglycan, leading to lysis
of the bacteria.
• Autolysis enables the release of
pneumolysin and large amounts of cell wall
fragments.
• The massive inflammatory response to these
peptidoglycan fragments is an important
component of the pathogenesis of
pneumococcal pneumonia and meningitis.

20. Pneumolysin:
• Intracellular membrane-damaging toxin released
by autolysis.
• Pneumolysin inhibits:
• neutrophil chemotaxis
• phagocytosis
• lymphocyte proliferation and immunoglobulin
synthesis.

21. • IgA1 protease:
• cleaves human IgA1 in the hinge region.
• Enables these pathogens to evade the protective
functions of the principal immunoglobulin isotype
of the upper respiratory tract
• Hyaluronate lyase
– Surface protein
• Facilitates tissue invasion by breaking down
the extracellular matrix components.

22. • One of the three leading causes of bacterial
meningitis
• Signs and symptoms are similar to those produced
by other bacteria
• Acute purulent meningitis may follow
pneumococcal pneumonia
• May also develop after trauma involving the skull
• Mortality and frequency of sequelae are slightly
higher than with other forms of pyogenic
meningitis

23. • Common causes of sinusitis and otitis media
– Otitis frequently occurs in children in
association with viral infection
• Chronic infection of the respiratory sinus sometimes extends
to the subarachnoid space to cause meningitis
• May cause endocarditis, arthritis, and peritonitis, usually in
association with bacteremia
• Pneumococci do not cause pharyngitis or tonsillitis

24. Laboratory Diagnosis
• Detection of the pathogen in appropriate test samples
– Smear: CSF, Sputum and others
– Culture: Blood, CSF, Sputum and others
• Stained Smears
– Gram-stained film of rusty-red sputum shows typical
organisms, many PMNs, and many red cells
– Capsule Swelling Tests
• Fresh emulsified sputum mixed with antiserum
causes capsule swelling (quellung reaction)

25. • Culture:
– grows well overnight on blood agar
– α – hemolytic colonies
– Colonies are bile soluble
– Inhibited by optochin (ethylhydrocupreine)
• Detection of capsular Ag in body fluids is
possible

26. • Immunity
– antibodies to capsular polysaccharide (type-specific)
• Treatment
– Penicillin G is the drug of choice
• Resistant strains due to modified penicillin-binding
proteins reported (not due to penicillinase)
• Resistance rate ~ 10%
– Penicillin resistant strains can be treated with:
• Erythromycin, vancomycin or quinolones
• High dose of third-generation cephalosporins
• Pneumococci remain susceptible to vancomycin

27. Vaccination
• Type-specific polysaccharides
– Probably provide 90% protection against bacteremic
pneumonia
– Pneumovax vaccin available:
• Contains 25 mg of the purified capsul
polysaccharides of each of the 23 most frequent
serovars
• protection of high-risk individuals older than two
years.
• 80 to 90 % of all isolated pneumococci have antigens
contained in this vaccine
• hepta-valent conjugate vaccine (PCV7):
– recommended for all children aged six weeks to five
years of age, to help prevent ear infections

28. • Heterogeneous collection of α-hemolytic and non-
hemolytic
• Have the basic features of streptococci but lack
specific Ags; toxins, & virulence factors of the
other group
• Optochin resistant and bile insoluble

29. • Genus Haemophilus
– Small, pleomorphic, Gm-negative bacilli or
coccobacilli
– Facultative anaerobes or fermentative.
– Require enriched media, blood or its derivative.
• X factor (i.e., hemin) and/or V factor (NAD or
NADP).
– Haemophilus influenzae type b is an important
human pathogen
– other species are NF of mucous membranes and
only occasionally cause disease.

30. • Haemophilus influenzae
– grow both aerobically and anaerobically.
– Its growth requires: hemin (X factor) and NAD
(V factor).
• six major serotypes identified(a–f) based on the
capsular polysaccharide antigen.
– some strains lack capsule and are referred to as
nontypable strains.
– subtype b (Hib) cause over 90% of all invasive
infections

31. – Unencapsulated strains may cause:
• Sinusitis, otitis media, and bronchitis
• may also cause pneumonia in children in
developing regions or in adults with immune
defects.
– Hib strains cause:
• meningitis, bacteremia, epiglottitis, septic
arthritis, pericarditis, as well as placentitis
and peripartum septicemia in mothers.
• A small proportion of invasive disease is
caused by other capsular types, notably, a
and f.

32. • About 50% of all reported invasive infections
caused by Hib are meningitis
• case-fatality rates may reach 40% in developing
countries.
• complications include:
– subdural effusions and CNS sequelae occur in
11% to 40% of survivors of Hib meningitis, with
deafness being a common finding.

33. • EPIDEMIOLOGY
– H. influenzae is the NF of nasopharynx
– spreads by airborne or direct contact person to
person.
– Nonencapsulated strains are frequently found in
the URT.
• up to 3/4 of healthy adults
– Carriage of Hib can occur up to 30% of children
in developing countries

34. • Diagnostic Laboratory Tests
• Specimens
– nasopharyngeal swabs, pus, blood, and spinal fluid
for smears and cultures.
• Direct Identification
– immunologic detection of H .influenzae antigens in
spinal fluid.
• Culture
– grown on chocolate agar typically (small, flat,
colorless/transparent) colonies appear.
– differentiated from related gram-negative bacilli by
its requirements for X and V factors
– and no hemolysis on blood agar

35. • Immunity
– maternal antibodies for infants under age 3
months
• Prevention
– Polysaccharide polyribose phosphate capsule
vaccines
• Treatment
– many strains of Hib are susceptible to
ampicillin, but up to 25% produce -lactamase
– all strains are susceptible to the third-
generation cephalosporins.

36. Streptococcus agalactiae (group B
Streptococci)
 Gm +ve cocci, short chains & diplococcal pairs
 Larger colonies
 β-hemolytic
 The only species that carries the Lancefield group B antigen
 Nine different capsular polysaccharide have been identified (Ia,
Ib, and II-VIII).
 Serotype III most frequently associated with neonatal infections ,
adult infections are distributed over the different serotypes.
 Resident in the GIT
 Members of the NF of 10 to 30% female genital organ

37.  May gain access to the amnoitic fluid or colonize the
newborn as it passes through the birth canal
 A major cause of sepsis and meningitis in neonates
 Risk is much higher when factors are present that:
◦ decreased infant’s innate resistance (prematurity) or
◦ increased chances of transmission (ruptured amniotic
membranes)

38.  Immunocompromised individuals:
◦ Infections of the skin & connective tissues, Sepsis, UTI,
Pneumonia & Peritonitis
Virulence factor
 Capsular polysaccharide
 Haemolysins
 C5a peptidase
 hyaluronidase (not all strains)

39. Clinical diseases
 defined by the age of the patient at presentation
Neonatal infection
i) Early-onset neonatal disease
 Occur within the first week of life, with a median age of 20 hrs
at the onset of illness
 Infection acquired during or shortly before birth from
organisms colonizing the maternal genital tract

40.  results from ascending spread of Str. agalactiae from the
vagina into the amniotic fluid
 Then aspirated by the infant, and results in septicaemia of
infant or mother or both.
 ~ 50% of infants delivered vaginally by carrier mothers
become colonized
◦ only 1 to 2% develop clinically evident infection

41.  Purulent Meningitis  most common manifestation
 but septic arthritis, osteomyelitis, conjunctivitis, sinusitis,
otitis media, endocarditis and peritonitis also occur
 Findings: fever, lethargy or irritability, poor feeding, and
seizures

42. Laboratory diagnosis
 Culture: blood, CSF, or other appropriate specimen
 Definitive identification: reaction to specific antiserum to the group
B carbohydrate antigen
 Biochemical tests (presumptive identification):
◦ hydrolysis of sodium hippurate (99% +ve)
◦ hydrolysis of bile esculin agar (99 to 100% -ve)
◦ bacitracin susceptibility (92% resistant)

43. Immunity
 Abs to the capsular polysaccharide afford protection
Treatment
 Penicillin is the treatment of choice (less susceptible than
GAS)
 Neonatal infections  often initially treated with
combinations of penicillin (or ampicillin) and an
aminoglycoside
 Prophylactic administration of ampicillin or penicillin
during delivery reduce the risk of infection

44.  Focused on reducing contact of the infant with the organism
 In colonized women:
◦ attempts to eradicate the carrier state  not successful
◦ intrapartum antimicrobial prophylaxis with penicillin or
ampicillin  reduce transmission and disease in high-risk
populations