MICROORGANISM

THAT CAUSE NERVOUS

SYSTEM INFECTION
Microbiology
Laboratory
Medical Faculty UB

BACTERIA
Streptococcus pneumoniae
Neisseria meningitidis
Haemophilus influenzae
Mycobacterium leprae
Clostridium tetani
Clostridium botulinum
Listeria monocytogenes

Mycobacterium leprae
this organisms was described by Hansen in 1873 (9 years

before Kochs discovery of the tubercle bacillus

it causes leprosy (Morbus Hansen, Hansens disease)
it has not been cultivated on artificial media (do not fulfill
Kochs postulate). It grows only in the footpads of mice,
armadillos, and tissue culture
spread through direct contact for a long time (as it occured
in certain family, firstly it was indicated as hereditary
disease)

Mycobacterium sp. (acid fast staining- ZN)

Morphology & Identification

acid fast straight/curved bacilli
acid fast staining: single or in groups, forming globi (packets

of cigars) acid fastness less than M.tuberculosis

patients that had been treated, will give beaded appearance
morphological index, can be used for follow up the
therapy
has a very long generation time, about 12 days
Diagnosis :
AF staining of scraping of skin, nasal mucosa, earlobe skin

LEPROMIN Test
Analog with tuberculin test (skin test using material

from lepromatous nodules)

Purpose: - evaluation of immunity to M.leprae
- helping to establish the diagnosis
- to know the result of therapy
- determine prognosis
Result:
Lepromin test (+) : cellular immunity: good
prognosis: good
Lepromin test (-) : cellular immunity: poor
prognosis: bad

Pathogenesis :
Are intracelullar pathogen
The lesions involve the cooler of the body: skin, nose,

pharynx, eyes, testicles, superficial nerves

Multiplies in mononuclear phagocytes mainly histocytes
on skin & Schwans cells in nerves, invades cells of the
myelin sheath of the peripheral nervous system
Long incubation period: several months years

Classification of leprosy:

TT
(Tuberculoid
Type)
Paucibacillary (WHO

system)
Macular skin lesion
The skin have lost of
sensation
Effectiveness of CMI
Recovery occurs
spontaneously

Borderline
BT
(Borderline
Tuberculoid)

BL
(Borderline
Leprosy)

LL
(Lepromatous
Leprosy)
- Multibacillary (WHO
system)
- Disfiguring nodules
form all over the body
- Lioned face
- Deformation of the
hand / foot
(mutilation)
- Lepromin test:
negative

Hypopigmented Macule in
Tuberculoid Leprosy

Arm Nodules in
Lepromatous Leprosy

Active, neglected nodulous

LL lesions on Face (lioned face)
Deformed
foot

Damaged
hands

Therapy
DDS ( Dapsone ) first line therapy
Rifampin, clofazimin, minocycline, fluoroquinolon

Prevention
Case finding
Isolation of patients
Immunization
Contact (especially in children) DDS

Clostridium tetani
Clostridium tetani, which causes tetanus, is worldwide in the soil and
in the feces of horses and other animals (spore form).
The symptom of tetanus are caused by an extremely potent
neurotoxin,
tetanospasmin, that is released by the vegetative bacteria. Extremely
small amounts of the toxin can be lethal for human

Morphology and Identification

is an obligately anaerob
endospore forming drumstick appearance
Gram positive rods

drumstick appearance

Clostridium tetani (Gram

stain)

Pathogenesis
Sporeform of C.tetani introduces the (small & deep) wound
Germination of the spores vegetative form produces toxin
(the toxin will reaches the CNS, but the bacterias do not spread from
the infection site and there is no inflammation)
The toxin initially binds to receptors on the presynaptic membranes
of motor neurons to the spinal cord and brain stem
The toxin diffuses to terminals of inhibitory cells from the brain stem
Release of the inhibitory (glycine and -aminobutyric acid) is blocked
The motor neurons are not inhibited muscle spasms & spastic paralysis

Clinical finding
Incubation period: 4-5 days to as many weeks
Characterized: tonic contraction of voluntary muscles:
- trismus, lockjaw (the mouth can not be opened)
- gradually, other voluntary muscle involved, resulting in generalized
tonic spasms (opisthotonus)
- any external stimulus may precipitate the spasms
The patient fully conscious and pain may be intense
Treatment of tetanus are not satisfactory prevention is important
Prevention: (1) active immunization
(2) proper care of wounds contaminated with soil, etc.
(3) prophylactic use of antitoxin
(4) administration of penicillin

(Tortora et al, 2009)

Clostridium botulinum
Clostridium botulinum can release a very poisonous toxin in

improperly canned food causes botulism (a form of

food poisoning)
First described as a clinical disease in the early 1800s
(botulus = sausages Latin word)
The spores are widespread in environment
In the food with alkalis or neutral condition and wound (at
anaerobic condition) spore germination

 strict anaerob
produce neurotoxin (exotoxin):
there are 7 antigenic types (A s/d G)
lethal dose for human < 1 g Ab is not produced
heat labile destroyed at 100oC
resistant to GIT enzymes and easy to be absorbed
target site : neuromuscular junction by inhibition of
the release of neurotransmitter (Ach)
muscular paralysis

Pathogenesis
Toxin in the food

Adsorbed from the gut

Binds to receptors of presynaptic membrane of
motor neurons of the PNS and cranial nerves
Proteolysis of the target SNARE protein in the neurons
Inhibits the release of Ach at the synaps
Paralysis

Clinical Importance
1. Botulism
incubation period 18 96 hours
symptoms :
- dry mouth, constipation, urine retention (because of
toxin affects ANS cholinergic)
- paralysis of ocular, pharinx, larinx, and respiratory muscle
therapy: ventilation, trivalent antitoxin (A,B,E)
prevention:
- canning food with the correct proccess
- cooking food at 100oC about 10 minutes
- cans (of food) which is swollen throw away

2. Infant botulism
occurs in baby at 8 weeks 8 months age
babys feeding contaminated by the m.o.
m.o.multiplying at colon of the baby
toxin
symptoms:
- acute flaccid paralysis (head, neck, facial, pharynx,
extremities muscle)
- death: caused by diaphragma paralysis
- is suspected as a causative agent of SIDS (sudden infant
death syndrome)
therapy: antitoxin, antimicrobial drug

Listeria monocytogenes
Cause stillbirth and neurological disease in animals long
before it was recognized as causing human disease
Excreted in animal feces, it is widely distributed in soil and
water
In recent years, listeriosis has changed from a disease of
very limited importance to a major concern for the food
industry and health authorities
Listeriosis has become the fourth most common cause of
bacterial meningitis

Morphology and Identification

is a short, Gram positive, non-spore forming rods
has a cell wall surface protein called internalin and ActA
has a tumbling motility at 22-28oC but not at 37oC
primary culture are done on blood agar small zone hemolysis
around the colonies
the motility at RT & hemolysis helping to differentiate listeria from
corynebacterium

Pathogenesis & Immunity

Contaminated foods (cheese, milk, vegetables)
Gastrointestinal tract:
internalin interacts with E-cadherin (a receptor on epithelial cells
phagocytosis phagolysosome the low pH activates
the bacteria to produce listeriolysin O escape into the cytoplasm
proliferation protein ActA induce host cell actin polymerization
push the bacterium to the cell membrane cause formation of
filopods (pseudopodia)
Ingested by adjacent cells, macrophage, and hepatocytes
Bacteria can move from cell to cell without being exposed to Ab,
Complement, or PMN

Cell-to-cell spread of L.monocytogenes. Notice that the bacterium

has caused the macrophage on the right, in which it resided , to form
a pseudopodia that is now engulfed by the Mo on the left (Tortora et al, 2009)

Clinical findings
Two basic forms:
1. Early onset-syndrome (granuloma infantseptica)
- is the result of infection in utero and is a disseminated form
- characterized by: neonatal sepsis, pustular lesions and granuloma
- death may be occur before or after delivery
2. Meningoencephalitis, bacteremia
- most commonly in adult patient with immunocompromized
Therapy
Ampicillin, Erythromycin, and trimethoprime-sulfamethoxazole
Cephalosporines & fluoroquinolones are not active against
L.monocytogenes

VIRUS
Polio virus
Rabies virus
ARBOVIRAL, eg. Japanese B encephalitis (JBE)
Eastern equine encephalitis (EEE)
Western equine encephalitis (WEE)

POLIOVIRUS
Poliomyelitis is an acute infectious disease

destruction of motor neurons in spinal cord result in

flaccid paralysis
Heine Medine Disease = Infantile paralysis = Acute
anterior poliomyelitis
from Greeks
poli : grey, myelos : spinal cord, itis : inflammation
Host range : human & monkey
Antigenic types :
- based on neutralizing antibody: Type 1 (type Brunhilde),

Pathogenesis
Mouth is the portal of entry of the vi.
Incubation period : usually 7-14 days (3 35 days)
Vi. present in the throat & stool before onset of illness
mouth
multiplication : oropharynx, tonsil, lymphnodes of neck,
and Peyers patches
viremia
to CNS via axons of PNS (peripheral nerves system)
( anterior horn cells of the spinal cord are most prominent,
posterior horn, gray ganglia, also the brain )
The changes of peripheral nerves & voluntary muscle
(the viruses does not multiply in muscle)

Clinical Findings
The response ranges:

from inapparent infection without symptom to a mild febrile,

and to severe and permanent paralysis
A. Abortive poliomyelitis :
- the most common form : minor illnes
- characterized by fever, malaise, drowsiness, nausea, vomiting,
constipation, shore-throat
- recovers in few days
B. Non-paralytic poliomyelitis (Aseptic meningitis) :
- in addition to the symptom above, the patient has stiffness &
pain of the back and neck
- recovery is rapid and complete

C. Paralytic poliomyelitis :

- predominating complaint is flaccid paralysis, usually

unilateral (cause of lower motor neuron damage)
- recovery usually occurs within 6 months with residual
paralysis lasting much longer
D. Progressive postpoliomyelitis muscle atrophy :

- a result of physiologic and aging changes in paralityc patient

- although is rare, it is a specific syndrome

Laboratory Diagnosis

- spesimen : throat swab, rectal swab

- isolation of vi : cell cultures cytopathic effect

 Immunity
- permanent to the type causing the infection
- low degree of heterotypic resistance between type 1 & 2
- the maternal Abs gradually disappear during the first 6 months of
the baby
- passively administered Abs lasts only 3 5 weeks
Treatment & Prevention
- symptomatic supplement

( no specific antiviral therapy)

- prevent ion : live vi. & killed vi. vaccine are available
equally well in preventing paralytic infection
- waste water treatment and sanitation

POLIO VACCINE

Salk vaccine (killed vi.)

- from PMK cell culture
- periodic booster immunization will be necessary
- induce humoral immunity, not induce local intestinal immunity
polio vi. still able multiply in the gut
- administered by injection ( i.m.)

Sabine vaccine (live attenuated-vi.) :

- from PMK & human diploid cells
- oral administration
- induce humoral & local intestinal immunity
- vi. multiplies, infects in the gut
disseminate the immunity to community
mutation of the vaccine vi
paralytic disease (rare)
- requires multiple doses to establish permanent immunity
- other enteroviruses may be block the immunity

RABIES

is a disease that almost always results in fatal encephalitis

from Latin = madness
worldwide, humans usually are infected from the bite of
an infected animal especially dog or bats
the immune response is ineffective because the viruses in
the wound in numbers too low to provoke it; also they do not
travel through the bloodstream or lymphatic system

Once the virus enters

the PNS, is not
asccesible to the
immune system until
cells of the nerve
cells to be destroyed

Pathomechanism of rabies infection (Tortora et al, 2009)

Morphology & Identification

Genus: Lyssavirus
ss RNA, bullet shaped (75 x 180 nm)
envelope (+), spikes (+)
intracytoplasmic replication
rabies virus produces a specific cytoplasmic inclusion
bodies, negri bodies, in infected nerve cells
released by budding formation

The incubation period, may depend on the:

amount of inoculum
attacked tissue
condition of host
distance of the virus has to travel from its point of entry
to the brain

Clinical Finding

primary infection attacked by animal

as an acute encephalitis fulminant, and fatal
3 phases of the disease:

1. Prodromal not specific,

2. Acute neurologic phase : catalepsy, hydrophobia
3. Comma death,because of respiratory paralysis

Laboratory Diagnosis

Antigen detection & negri bodies

Isolation & viral identification
Serology
animal observation (during 10 days) :

if it has positive sign for encephalitis or abnormally

behaviour kill the animal, send the head to referral
laboratory (Biofarma - Bandung)

Prevention

Vaccination :

1. HDCV (human diploid cell vaccine).

2. NTV (nerve tissue vaccine), from goat.
3. DEV (duck embryo vaccine).
4. LAV (live attenuated vaccine), from
chicken embryo
Rabies antibody: from man or from horse

Control
To person who was bitten by wild animal

wash the wound with water and antiseptic, do not be

wound toilet:
sutured
if there is an indication gives rabies antibody
antimicrobial agent & ATS prophylaxis
animal observation
To animal
vaccination of pet dogs and cats

PRIONs
Prions can cause degenerative CNS diseases:

Kuru, CJD (Creutzfeldt-Jakob disease), bovine spongiform

encephalopathy, scrapie (sheep), fatal familial insomnia
(human), transmissible spongiform encephalopathies (TSE)
Are not conventional viruses infectivity is associated
with proteinaceous material devoid of detectable amounts
nucleic acid
An abnormally folded protein.

Although the etiologic agent may be recoverable from other

organs, the disease are confined to the nervous system

Clinical feature:
- neurodegeneration and spongiform changes
- long incubation periods (months to decades) followed by
chronic progressive disease (weeks to years)
- always fatal, with no known cases of remission or recovery
- no inflammatory, no immune response (not antigenic),
no production of interferon
- chronic inflammation induced by other factor (viruses,
bacteria, autoimmunity) may affect the prion pathoigenesis

FUNGI
Cryptococcus neoformans

CRYPTOCOCCOSIS
Agent: Cryptococcus neoformans
Yeast cells, 4-6 m, with thick polysaccharides-

glucoronoxylomannan capsules, 25 m
Habitat: soil, bird dropings
Major clinical findings: chronic meningitis, with spontaneous
remissions and exacerbations; may resemble brain tumor,
brain abscess

Cryptococcus neoformans
This yeastlike fungus has an unusually thick capsule.
(suspending the cells in dilute India ink) (Tortora et al, 2009)

Bilateral patchy
infiltrates
Cutaneous cryptococcosis

Diagnosis
Specimens: CSF, sputum, blood, urine
Direct examination using India ink thick capsule
Culture: medium + cycloheximide
Serology

Therapy
Amphotericin B
Flucytosine
Fluconazole

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