4. Nervous System Infection

7/25/2019 4. Nervous System Infection

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MICROORGANISM

THAT CAUSE NERVOUSSYSTEM INFECTION

MicrobiologyLaboratory

Medical Faculty U



BACTERIAStreptococcus pneumoniae

Neisseria meningitidis

Haemophilus influenzae

Mycobacterium leprae

Clostridium tetani

Clostridium botulinumListeria monocytogenes



Mycobacterium leprae

this organisms was described by Hansen in 1873 (9 years

before Koch’s discovery of the tubercle bacillus

it causes leprosy (orbus Hansen! Hansen’s disease"

it has not been cultivated on artificial media (do not fulfill

Koch’s postulate). #t 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$ %&"



Morphology & Identification

acid fast straight'curved bacilli

acid fast staining single or in groups! forming globi (pac)ets

of cigars" acid fastness less than M.tuberculosis

patients that had been treated! will give beaded appearance morphological inde*! can be used for follow up the

therapy

has a very long generation time! about 1+ daysDiagnosis :• ,- staining of scraping of s)in! nasal mucosa! earlobe s)in



LEPROMIN Test

,nalog with tuberculin test (s)in test using materialfrom lepromatous nodules"

.urpose $ evaluation of immunity to M.leprae

$ helping to establish the diagnosis $ to )now the result of therapy

$ determine prognosis

• /esult

0epromin test (" cellular immunity good

prognosis good

0epromin test ($" cellular immunity poor

prognosis bad



Pathogenesis :

,re intracelullar pathogen

2he lesions involve the cooler of the body s)in! nose!

pharyn*! eyes! testicles! superficial nerves

ultiplies in mononuclear phagocytes mainly histocytes

on s)in 4chwan’s cells in nerves! invades cells of the

myelin sheath of the peripheral nervous system

0ong incubation period several months 5 years



Classification of leprosy:

TT

(2uberculoid

2ype" .aucibacillary (6H

system" acular s)in lesion 2he s)in have lost of

sensation ffectiveness of # /ecovery occurs

spontaneously

LL

(0epromatous

0eprosy"-ultibacillary (6H

system"-:isfiguring nodules

form all over the body

- 0ioned face-:eformation of the

hand ' foot

(mutilation"- 0epromin test

negative

Borderline

BL

(;orderline

0eprosy"

BT

(;orderline

2uberculoid"



Hypopigmented Macule in

Tuberculoid Leprosy

Arm Nodules in

Lepromatous Leprosy



Active, neglected nodulousLL lesions on Face (lioned face"

Deformed

foot

Damaged

hands



Therapy

::4 ( :apsone " first line therapy/ifampin! clofa<imin! minocycline! fluoro=uinolon

Prevention

ase finding

#solation of patients#mmuni<ation

ontact (especially in children" ::4



Clostridium tetani

• Clostridium tetani, which causes tetanus! is worldwide in the soil and

in the feces of horses and other animals (spore form">• 2he symptom of tetanus are caused by an e*tremely potent

neuroto*in!

tetanospasmin! that is released by the vegetative bacteria> *tremely

small amounts of the to*in can be lethal for human

Morphology and Identification

is an obligately anaerob endospore forming drumstic) appearance ?ram positive rods



Clostridium tetani !Gra"#tai$%

drumstick appearance



Pathogenesis

4poreform of C.tetani introduces the (small deep" wound

?ermination of the spores vegetative form produces to*in

(the to*in will reaches the &4! but the bacterias do not spread from

the infection site and there is no inflammation"

2he to*in initially binds to receptors on the presynaptic membranes

of motor neurons to the spinal cord and brain stem

/elease of the inhibitory (glycine and @$aminobutyric acid" is bloc)ed

2he motor neurons are not inhibited muscle spasms spastic paralysis

2he to*in diffuses to terminals of inhibitory cells from the brain stem



Clinical finding

#ncubation period A$B days to as many wee)s haracteri<ed tonic contraction of voluntary muscles

$ trismus! loc)Caw (the mouth can not be opened"

$ gradually! other voluntary muscle involved! resulting in generali<ed

tonic spasms (opisthotonus" $ any e*ternal stimulus may precipitate the spasms 2he patient fully conscious and pain may be intense

2reatment of tetanus are not satisfactory prevention is important

.revention (1" active immuni<ation(+" proper care of wounds contaminated with soil! etc>

(3" prophylactic use of antito*in

(A" administration of penicillin



(Tortora et al !""#$



Clostridium botulinum can release a very poisonous to*in inimproperly canned food causes botulism (a form offood poisoning"

-irst described as a clinical disease in the early 18DDs

(botulus E sausages 0atin word"

2he spores are widespread in environment

#n the food with al)alis or neutral condition and wound (atanaerobic condition" spore germination

Clostridium botulinum



● strict anaerob

F produce neuroto*in (e*oto*in"there are 7 antigenic types (, s'd ?"lethal dose for human G 1 µg ,b is not producedheat labile destroyed at 1DDoresistant to ?#2 en<ymes and easy to be absorbedtarget site neuromuscular Cunction by inhibition of

the release of neurotransmitter (,ch"

muscular paralysis



Pathogenesis

2o*in in the food

,dsorbed from the gut

;inds to receptors of presynaptic membrane of

motor neurons of the .&4 and cranial nerves

.roteolysis of the target 4&,/ protein in the neurons

#nhibits the release of ,ch at the synaps

.aralysis



1. Botulism

incubation period 18 5 9 hours symptoms

$ dry mouth! constipation! urine retention (because of

to*in affects ,&4 cholinergic" $ paralysis of ocular! pharin*! larin*! and respiratory muscle therapy ventilation! trivalent antito*in (,!;!"

prevention$ canning food with the correct proccess

$ coo)ing food at 1DDo about 1D minutes $ cans (of food" which is swollen throw away

Clinical Importance



2. Infant botulism

occurs in baby at 8 wee)s 5 8 months age baby’s feeding contaminated by the m>o>

m>o>multiplying at colon of the baby to*in

symptoms$ acute flaccid paralysis (head! nec)! facial! pharyn*!

e*tremities muscle"

$ death caused by diaphragma paralysis

$ is suspected as a causative agent of 4#:4 (Isudden infantdeath syndromeJ"

therapy antito*in! antimicrobial drug



Listeria monocytogenes

ause stillbirth and neurological disease in animals long

before it was recogni<ed as causing human disease

*creted in animal feces! it is widely distributed in soil and water #n recent years! listeriosis has changed from a disease of

very limited importance to a maCor 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! ?ram positive! non$spore forming rods has a cell wall surface protein called internalin and ActA

has a tumbling motility at ++$+8o but not at 37o primary culture are done on blood agar small <one hemolysis

around the colonies the motility at /2 hemolysis helping to differentiate listeria from

corynebacterium



Pathogenesis & Immunity

ontaminated foods (cheese! mil)! vegetables"

?astrointestinal tract

internalin interacts with $cadherin (a receptor on epithelial cells

phagocytosis

phagolysosome

the low pH activatesthe bacteria to produce listeriolysin escape into the cytoplasm

proliferation protein ,ct, induce host cell actin polymeri<ation

push the bacterium to the cell membrane cause formation of

filopods (pseudopodia"

#ngested by adCacent cells! macrophage! and hepatocytes

;acteria can move from cell to cell without being e*posed to ,b!

omplement! or .&



ell!to!cell spread of L.monocytogenes. &otice that the bacterium

has caused the macrophage on the right! in which it resided ! to form

a pseudopodia that is now engulfed by the o on the left (2ortora et al, +DD9"



Clinical findings

2wo basic forms

1> arly onset$syndrome (granuloma infantseptica"

$ is the result of infection in utero and is a disseminated form

$ characteri<ed by neonatal sepsis! pustular lesions and granuloma

$ death may be occur before or after delivery +> eningoencephalitis! bacteremia

$ most commonly in adult patient with immunocompromi<ed

Therapy ,mpicillin! rythromycin! and trimethoprime$sulfametho*a<ole ephalosporines fluoro=uinolones are not active against

L.monocytogenes



VIRUS

.olio virus

/abies virus ,/;#/,0! eg> Lapanese ; encephalitis (L;"

astern e=uine encephalitis ("

6estern e=uine encephalitis (6"



POLIOVIRUS

• .oliomyelitis is an acute infectious disease destruction of motor neurons in spinal cord result in

flaccid paralysis

Heine edine :isease E #nfantile paralysis E ,cute

anterior poliomyelitis

from ?ree)’s

poli grey! myelos spinal cord! itis inflammation

• Host range human mon)ey

• ,ntigenic types

$ based on neutrali<ing antibody 2ype 1 (type ;runhilde"!



Pathogenesis

outh is the portal of entry of the vi>• #ncubation period usually 7$1A days (3 5 3B days"

• i> present in the throat stool before onset of illness

mouth

multiplication # oropharyn*! tonsil! lymphnodes of nec)! and .eyer’s patchesviremia

to $% via a&ons of '$% (peripheral nerves s)stem" ( anterior horn cells of the spinal cord are most prominent! posterior horn! gray ganglia! also the brain "

The changes of peripheral nerves * voluntar) muscle(the viruses does not multiply in muscle"



Clinical %indings

• 2he 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$ characteri<ed by fever! malaise! drowsiness! nausea! vomiting!

constipation! shore$throat

$ recovers in few daysB. Non-paralytic poliomyelitis (Aseptic meningitis) :$ in addition to the symptom above! the patient has stiffness

pain of the bac) and nec)$ recovery is rapid and complete



. 'aral)tic poliom)elitis #

$ predominating complaint is flaccid paralysis! usually

unilateral (cause of lower motor neuron damage"

$ recovery usually occurs within months with residual

paralysis lasting much longer

D. 'rogressive postpoliom)elitis muscle atroph) #

$ a result of physiologic and aging changes in paralityc patient

$ although is rare! it is a specific syndrome

• a'oratory 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 +$ the maternal ,bs gradually disappear during the first months of

the baby$ passively administered ,bs lasts only 3 5 B wee)s

• Treatment & Prevention

- symptomatic supplement ( no specific antiviral therapy"

! prevent ion live vi> )illed vi> vaccine are available

e=ually well in preventing paralytic infection

! waste water treatment and sanitation



%al+ vaccine (+illed vi."

$ from .K cell culture $ periodic booster immuni<ation will be necessary

$ induce humoral immunity! not induce local intestinal immunity

polio vi> still able multiply in the gut

! administered by inCection ( i>m>"

Sabine vaccine (live attenuated-vi.) :

$ from .K 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"

$ re=uires multiple doses to establish permanent immunity

$ other enteroviruses may be bloc) the immunity

PI )*CCI+,



RAIES

is a disease that almost always results in fatal encephalitis from 0atin E madness

worldwide! humans usually are infected from the bite of an infected animal 5 especially dog or bats the immune response is ineffective because the viruses in

the wound in numbers too low to provo)e itM also they do not

travel through the bloodstream or lymphatic system



.athomechanism of rabies infection (2ortora et al! +DD9"

nce the virus enters

the .&4! is not

asccesible to the

immune system until

cells of the nervecells to be destroyed



Morphology & Identification

• ?enus 0yssavirus

• ss /&,! bullet shaped (7B * 18D nm"

• envelope ("! spi)es ("• intracytoplasmic replication

• rabies virus produces a specific cytoplasmic inclusion

bodies! negri bodies! in infected nerve cells

• released by budding formation



2he incubation period! may depend on the amount of inoculum

attac)ed tissue

condition of host

distance of the virus has to travel from its point of entry

to the brain



Clinical %inding

primary infection attac)ed by animal

as an acute encephalitis fulminant! and fatal

3 phases of the disease

1> .rodromal

not specific!+> ,cute neurologic phase catalepsy! hydrophobia

3> omma death!because of respiratory paralysis



a'oratory Diagnosis

,ntigen detection negri bodies

#solation viral identification

4erology

animal observation (during 1D days" if it has positive sign for encephalitis or abnormally

behaviour )ill the animal! send the head to referrallaboratory (;iofarma $ ;andung"



Prevention

accination

1> H: (human diploid cell vaccine">

+> &2 (nerve tissue vaccine"! from goat>

3> : (duc) embryo vaccine">

A> 0, (live attenuated vaccine"! from

chic)en embryo

/abies antibody from man or from horse



To person -ho -as 'itten 'y -ild animal

wash the wound with water and antiseptic! do not be wound toilet

sutured if there is an indication gives rabies antibody antimicrobial agent ,24 prophyla*is animal observation

To animal• vaccination of pet dogs and cats

Control



&RION#

.rions can cause degenerative &4 diseases

Kuru! L: (reut<feldt$La)ob disease"! bovine spongiform

encephalopathy! scrapie (sheep"! fatal familial insomnia

(human"! transmissible spongiform encephalopathies (24"

,re not conventional viruses infectivity is associated

with proteinaceous material devoid of detectable amountsnucleic acid

,n abnormally folded protein>



,lthough the etiologic agent may be recoverable from other

organs! the disease are confined to the nervous systemlinical feature

$ neurodegeneration and spongiform changes

$ long incubation periods (months to decades" followed by

chronic progressive disease (wee)s to years"

$ always fatal! with no )nown 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



CRY&TOCOCCOSIS

,gent Cryptococcus neoformans

Neast cells! O A$ Pm! with thic+ polysaccharides$

glucorono*ylomannan capsules! Q +B PmHabitat soil! bird dropings

aCor clinical findings chronic meningitis! with spontaneous

remissions and e*acerbationsM may resemble brain tumor!

brain abscess



Cryptococcus neoformansThis yeastlike fungus has an unusually thick capsule.

(suspending the cells in dilute India ink$ (Tortora et al !""#$



;ilateral patchyinfiltrates

utaneous cryptococcosis



Diano!i!

4pecimens 4-! sputum! blood! urine:irect e*amination using #ndia in) thic) capsuleulture medium cyclohe*imide4erology

"#erap$,mphotericin ;-lucytosine

-lucona<ole



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4. Nervous System Infection