Central Nervous System Infections

1

• Central Nervous System Infections

2
INTRODUCTION

• Central nervous system infections are usually
• 1- Blood-borne invasion most common
• (e.g. polioviruses or Neisseria
  meningitidis)
• 2- Invasion via peripheral nerves less common
  
• (e.g. herpes simplex, varicella-zoster,
  rabies)

3
INTRODUCTION

• 1- Blood-borne invasion takes place across
• - blood-brain barrier (encephalitis)
• - blood-cerebrospinal fluid (CSF) barrier
  (meningitis).
• Microbes can traverse these barriers by
• - Infecting the cells that comprise barrier.

4
INTRODUCTION

• 2-Invasion via peripheral nerves
• Herpes simplex virus (HSV) and varicella-zoster
  virus (VZV) present in skin or mucosal lesions
  travel up axons to reach the dorsal root ganglia.
  
• Rabies virus, introduced into muscle tissues
  by
• - bite of a rabid animal.
• - It enters peripheral nerves and travels to
  CNS,
• to reach the neurons.

5
Pathologic consequences of CNS infection

• In CNS viruses infect neural cells, sometimes
  showing a marked preference.
• Polio and rabies viruses invade neurons. CJD
  virus invades oligodendrocytes.
• Spread of infection is direct from cell to cell
  along established nervous pathways.
• Bacteria and protozoa induce brain abscesses.

6

• Meningitis

7
Introduction

• Meningitis is one of the most terrifying
  disease.
• It can be fatal in hours.
• Early symptoms resemble
• self-limiting conditions
• (flu and colds).

8
Definition of Meningitis

• A general name for inflammation of
• a) Meninges
• Sheaths that cover brain and spinal cord
• b) Cerebrospinal fluid
• Fluid that circulates in the spaces
• in and around brain and spinal cord
• Meningitis can be caused by
• infectious or non-infectious agents
• Infectious agents include
• bacteria, viruses, fungi, protozoa
• and rickettsia.

9
Causes of Meningitis

• Bacterial Infections
• Viral Infections
• Fungal Infection
• Mycobacterium tuberculosis
• Trauma to head or spine

10
Causes of Meningitis (cont.)
Most common causes of meningitis are a)
Bacterial infections (Septic meningitis)
may result in death or brain damage. b)
Viral infections (Aseptic meningitis)
usually resolve without treatment.
11
Bacterial Meningitis (Septic Meningitis)

• - Pneumococcal, Streptococcus pneumoniae (38)
• Meningococcal, Neisseria meningitidis (14)
• Haemophilus influenzae (4)
• Staphylococcal, Staphylococcus aureus (5)
• - Tuberculous, Mycobacterium tuberculosis

12
Symptoms of meningitis
Adults and children
Babies
Neonates and the elderly often present atypically
13
Neisseria Meningitidis (Meningococci)

• Meningococcus The causative organism of
  epidemic cerebrospinal meningitis.
• Aerobic gram-negative diplococci.
• 13 serogroups based on polysaccharide capsule.
• Most invasive disease caused by
• serogroups A, B, C, Y, and W-135.

14
Pathogenesis Of Meningococcal Meningitis

• Organism colonizes membranes of nasopharynx.
• Organism may reach blood stream producing
  meningococcemia, the symptoms may be like upper
  respiratory tract infection.
• Meningococcemia may occur with or without
  meningitis.
• Meningitis is the most common complication of
  meningococcemia.

15
Clinical Features Of Meningococcal Meningitis

• Transmission respiratory droplets
• Incubation period 3-4 days
• Clinical Features
• - Fever
• - Vomiting
• - Headache
• - Stiff neck
• - Hypotension, and rash

16
Meningococcal Disease Laboratory Diagnosis
Specimen - Cerebrospinal fluid (CSF) .
Fluid usually collected from arachnoid
space. . A sterile needle is inserted
between 4th and 5th lumbar vertebrae and
the CSF is allowed to drip into a dry
sterile container - Blood
17
CSF

• Appearance Cells (WBCs) Protein
  Glucose
• Normal CSF Clear colorless Below 5x106/l
  15-40mg 45-72mg
• Pyogenic Purulent/cloudy usually many
  High very low Bacterial
  pus cells
• Meningitis
• Viral Clear/slightly Raised
  Normal or usually Meningitis
  turbid lymphocytes increased
• Tuberculosis Clear/slightly Raised High
  reduced Meningitis turbid
  lymphocytes

18
Meningococcal DiseaseLaboratory Diagnosis

• Bacterial culture
• on chocolate agar in 5-10 CO2
• Gram stain
• Gm ve diplococci intracellular in pus
• Blood culture give positive results
• Detection of meningococcal polysaccharide
  antigens in CSF
• PCR test for detection of meningococcal DNA in
  blood or serum

19
Neisseria Meningitidis Management

• Penicillin G is drug of choice for patients
• Chloramphenicol and cephalosporins for
• - persons allergic to penicillin or
• - strain is resistant to penicillin
• Chemoprophylaxis for contacts
• - Rifampicin, orally twice daily for 2 days
• - Ciprofloxacin as a single oral dose

20
Vaccination For Meningitis

• - A polyvalent vaccine from the capsular
  polysaccharide of groups A, C, Y and
• W-135 strains.
• - The vaccine does not include group B
  polysaccharide.

21
Viral Meningitis (Aseptic meningitis)

• Etiological Agents
• Enteroviruses, most common (Coxsackie and
  Echovirus)
• Adenovirus
• Arbovirus
• Measles virus
• Herpes Simplex virus
• Varicella Zoster virus
• Modes of transmission
• Primarily from person to person
• Arthopod vectors for Arboviruses
• Incubation Period
• Enteroviruses 3-6 days
• Arboviruses 2-15 days
• Most patients recover completely on
  their own

22

• Tetanus

23
Introduction

• Tetanus (Greek Word) Tetanos means to contract
• Tetanus is an acute, often fatal, disease
  caused by
• An exotoxin produced by Clostridium tetani
• Toxins are produced with growth of bacteria.
• Tetanospasmin toxin
• - Estimated human lethal dose (2.5
  ng/kg).

24
Clostridium tetani

• Clostridium tetani
• - Anaerobic gram-positive bacilli
• - Spore-forming bacteria
• It is characterized by
• . Generalized rigidity
• . Convulsive spasms of skeletal muscles
• . Muscle stiffness of jaw and neck
  (lockjaw)
• It is prevented by immunization with tetanus
  toxoid

25
Reservoir Of Cl. Tetani

• Spores of Cl. tetani are found in soils and
  animal feces.
• Spores are very resistant to - heat
• - radiation
• - chemicals
• - drying
• Spores can survive for a long time in
  environment (months or years)

26
Mode Of Transmission

• Transmission by contaminated wounds
• - Surgical wounds
• - Deep puncture wounds
• - Crush wounds
• - Burns
• - Dental infection
• - Animal bites
• - Delivery or abortion

27
Pathogenesis Of Tetanus

• At wound, blood supply to tissues decreases.
• Cl. tetani spores germinate into active
  vegetative cell that grows and produces
• Tetanospasmin toxin

28
Pathogenesis (contd)

• Tetanospasmin is a lethal neurotoxin.
• It Induces spastic paralysis by
• inhibiting release of inhibitory
  neurotransmitters
• which lead to uncontrolled muscle contractions
• (spastic paralysis)

29
Clinical Picture of Tetanus

• Lock jaw
• Convulsive muscle contractions of the jaw
• Opisthotonos
• Extension of lower extremities, flexion of
  upper extremities and arching of the back.
• Neck rigidity
• Death
• Heart or respiratory failure

30
Diagnosis of Tetanus

• Tetanus is suspected upon exposure to a bite or
  a wound.
• Diagnosis depends on
• Clinical findings and history.
• Because Cl. tetani exhibits such sensitivity to
  O2
• it is very difficult to recover and/or grow
  from clinical
• specimens.

31
Treatment of Tetanus

• Antitoxin is administered
• Muscle relaxants
• Supportive therapy (ventilator)
• Cleansing of the wound

32
Prevention of Tetanus

• A highly effective vaccine is available.
• Tetanus immunity is achieved using
• - A formalized tetanus toxoid.
• - Toxoid is administered as part of DTP
  vaccine
• Boosters every 10 yrs.

33
Botulism
34
Microbiology

• Clostridium botulinum
• Large, anaerobic Gram-positive bacilli
• Spore-forming
• Rarely infects humans
• Produces potent neurotoxin
• - 7 types (A-G)
• - Types A, B, E are the most common

35
Botulism

• Cl. botulinum spores widespread in
• - soil
• - contaminated vegetables
• - meat and fish
• Canned or preserved foods
• (without adequate sterilization)
• - Spores survive and germinate in
• anaerobic environment
• - Formation of toxin

36
Pathogenesis

• Botulinus toxin is ingested absorbed from gut
  into blood.
• It acts on peripheral nerve synapses by blocking
  release of acetylcholine.
• It affects motor and autonomic nervous system.
• If the organism is ingested by infants, it
  multiplies in gut and produce toxin, causing
  infant botulism.

37
Clinical Features

• Incubation 12-72 hours
• Classic syndrome
• Acute symmetric cranial nerve palsies
• - Blurry vision, ptosis, dysphasia
• Descending flaccid paralysis
• Complete skeletal muscle paralysis
• Respiratory failure
• Autonomic urinary retention
• Normal mentation

38
Diagnosis

• Diagnosis of botulism is mainly clinical
• Laboratory confirmation
• Specimens Contaminated food
• Patient's serum
• ELISA

39
Treatment

• Supportive care
• - Mechanical ventilation
• Passive immunization (antitoxin)
• - Trivalent antitoxin (Types A, B and E
  toxins).
• Complications
• - Serum sickness (9 )
• - Anaphylaxis (2 )

40
Rabies
41
Rabies Virus

• Rabies is an acute infection of the CNS which is
  fatal. The main animals involved are dogs, foxes
  and bats.

42
Pathogenesis

• It is transmitted by the bite of a rabid animal,
  usually a dog.
• Following inoculation, the virus replicates in
  the striated or connective tissue at the site of
  inoculation and enters the peripheral nerves
  through the neuromuscular junction.
• It then spreads from the peripheral nerves to the
  CNS.
• Terminally, there is widespread CNS involvement
  but few neurons infected with the virus show
  structural abnormalities.

43
Laboratory Diagnosis

• Histopathology - Negri bodies are diagnostic of
  rabies.
• Rapid virus antigen detection - The Direct
  Fluorescent Antibody test (DFA) is commonly used
  in which corneal impressions or neck skin biopsy
  are taken.
• Virus cultivation - The most definitive means of
  diagnosis is by virus cultivation from saliva and
  infected tissue.
• Virus cultivation can be done using cell cultures
  or more commonly, the specimen is inoculated
  intra-cerebrally into infant mice.  
• Serology - circulating antibodies appear slowly
  but they are usually present by the time of onset
  of clinical symptoms.

44
Negri Body in neuron cell (left) and Positive DFA
test (right).
45
Management and Prevention

• Pre-exposure prophylaxis - Inactivated rabies
  vaccine is given to persons at increased risk of
  rabies e.g. vets, animal handlers, laboratory
  workers etc.
• Post-exposure prophylaxis - In cases of animal
  bites, dogs and cats in a rabies endemic area
  should be held for 10 days for observation.
• If signs develop, they should be killed and their
  tissues examined.

46
Post-exposure Prophylaxis

• Wound treatment - surgical debridement should be
  carried out.
• Passive immunization - human rabies
  immunoglobulin is given around the area of the
  wound and an i.m. dose to confer short term
  protection.
• Active immunization - The human diploid cell
  vaccine is usually administered into the deltoid
  region, and 5 doses are usually given.
• Combined treatment with rabies immunoglobulin and
  active immunization is much more effective than
  active immunization alone.

47
Rabies Vaccines

• The vaccines which are available for humans are
  inactivated whole virus vaccines.
• Nervous Tissue Preparation
• Duck Embryo Vaccine
• Human Diploid Cell Vaccine (HDCV)

48
Control of Rabies

• Canine rabies accounts for more than 99 of all
  human rabies. Control measures against canine
  rabies include
• Stray dog control.
• Vaccination of dogs.
• Quarantine of imported animals.