CNS Disorders (CD Nursing)

7/27/2019 CNS Disorders (CD Nursing)

1/315

CNS AFFECTING THECNS


2/315

TETANUS


3/315

Tetanus

A neurological disease characterised by increased muscle tospasms.

Caused by CLOSTRIDIUM TETANI

An anaerobic, motile, gram positive rod that forms oval, colterminal spores tennis racket or drumstick shape.


4/315

A. IMPORTANT INFORMATION

1. Infectious but not contagious2. Brought about by direct inoculation of material containing

causative agent

3. Always a serious diseasefatal up to 60% of unimmunize

usually within 10 days of onset. When symptoms develop

days, the prognosis is poor.


5/315

B. OTHER NAMES

Lockjaw Tetanos a Greek word to strech

First described by Hippocrates & Susruta


6/315

C. CAUSATIVE AGENT

1. A common inhabitant of the soil especially if fertilized wit2. Anaerobic (does not grow in the presence of free oxygen),

bacillus with round terminal spore with slender body givin

drumstick appearance

3. The organism comes in 2 forms, spore forming and the veg

form

4. Spores are extremely resistant to heat and ordinary antisep

5. Multiplies only at the site of the wound


7/315

2 Forms of Clostridium tetani

1.Vegetative: Slender, gram positive, nonencapsulated, motileanaerobic

Susceptible to bactericidal effect of heat, chemical disinfectantibiotics

Pathogenic form

2. Sporulated

Bulge at one end; drumstick appearance

Highly resistant to disinfection by chemicals or heat


8/315

C. CAUSATIVE AGENT

6. The organism releases 2 types of toxins:

a. Tetanolysin

Dissolves/destroys the red blood cells Results to anemia

Thus, patient is pale-looking

b. Tetanospasmin

Causes muscle spasm

Acts on MYONEURAL JUNCTION of the muscles and on INTERNUNCIALFIBERS of the spinal cord and thebrain.

Results into multiple muscle spasms

Inhibits the spastic muscle from sending transmissions to th

which would inhibit progression of spasms. Due to this, adja

muscles will also undergo spasm similar to a chain reaction

domino reaction.


9/315

In the wound, there would be an inflammatory responscardinal signs of local inflammation):

a. Ruborredness

b. Calorheat

c. Tumorswelling

d. Dolor

paine. Functio laesaloss of function


10/315

It is found worldwide in soil, in inanimate environment, in afeces & occasionally human feces.


11/315


12/315

D. PREDISPOSING FACTORS

1. More in the tropics2. Newborns whose method of delivery and umbilical cor

not aseptic

3. Compound fracture

4. Following surgeries; any punctured wound; infected w

burns; tooth decay5. Bites/scratches

6. Women are poorer risks than men, so are the very youn

the very old


13/315

E. EPIDEMIOLOGY

Occurs sporadically Affects unimmunized, partially immunized & fully immunize

to maintain adequate immunity with booster doses of vacci

Although it is an entirely preventable disease by immunizatiburden of disease worldwide is great.


14/315

As reporting is inaccurate & incomplete, particularly

in devoleping countries, W.H.O considers reportedcases to be an underestimate & takes case/deathestimates to assess the burden of disease.

In 2002, the estimated deaths in all age groups2,13,000 of which 1,80,000 were attributable toneonatal tetanus.

More common in areas where soil is cultivated, inrural areas, in warm climates, during summer, amonmales.


15/315

F. INCUBATION PERIOD

1. Commonly 5-10 days but may vary from 2 days to severallonger, depending on the extent, location, and character of

wound (3-21-28 days)

2. A short incubation period gives a bad prognosis

3. The longer the incubation period, the greater the probabilit

recovery


16/315

CONCEPT

The shorter the incubation period, the poorer the progn Shorter incubation period is 2-3 days.

An incubation period of one month has a better prognos

incubation period of 2-3 days.


17/315

F. SOURCES OF INFECTION

1. Animal and human feces (manure). The organisms are fouintestinal wall of herbivorous animals, including man.

2. Soil and dust

3. Plaster of Paris, unsterile sutures, pins, rusty metals, scisso


18/315

G. MODE OF TRANSMISSION

1. Break in skin integrity

through punctured wound that is contaby dust, soil, or animal excreta containing spores of Clostridum

a. Rugged traumatic wounds and burns

b. Umbilical cord stump in newborn especially for babies deliv

home with faulty cord dressing; babies delivered to mothers

Tetanus toxoid immunizationc. Unrecognized wounds (cleaning of the ears with sharp mate

d. Dental extraction, circumcision, ear piercing


19/315

G. MODE OF TRANSMISSION

Range of injuries & accidentstrivial pin prick, skin abrasiopuncture wounds, burns, human bites, animal bites & stingunsterile surgery, IUD, bowel surgery, dental extractions, inunsterile division of umbilical cord, compound #, otitis mechr.skin ulcers, eye infections, gangrene

NOT TRANSMITTED FROM PERSON TO PERSON


20/315

H. PATHOPHYSIOLOGY

C. tetanienters body through a wound

causes local and tissue necrosis in anaerobic conditions spores g(reproduce) toxins produced (TETANOSPASMIN &TETANOLYSIN) disseminated via blood and lymphaacts at several sites:

1. Central nervous system

2. Spinal cord

3. Brain

4. Sympathetic nervous system


21/315

H. PATHOPHYSIOLOGY

While reproducing, they also release toxins that enter the blooand the lymphatics and eventually spread into the central nerv

system, or absorbed by the motor nerve ending and passes up

the axon cylinder, to the anterior horn cells of the spinal cord.

stimulates contraction of the muscles supplied by the neurons

the toxin diffuses.


22/315

H. PATHOPHYSIOLOGY

Contamination of wounds with spores of C.tetani.

Germination & toxin production in wounds with low oxidreduction potential (devitalized tissues, active infection )

Tetanospasmin (neurotoxin)

Tetanolysin (hemolysin)


23/315

Tetanospasmin (exotoxi) produced locally , released into blo

Binds to peripheral motor neuron terminals & nerve cells ofof spinal cord

The toxin after entering axon , transported to nerve cell bodstem & spinal cordretrograde intraneuronal transport

Toxin migrates across synapse presynaptic terminals- blorelease ofGlycine & GABA from vesicles.


24/315

The blocking of neurotransmitter release by Tetanospasmincleavage of Synaptobrevin essential for proper fn of synaprelease apparatus

With diminished inhibition resting firing rate of alpha motneurons increasesrigidity

Lessened activity of reflexes which limit polysynaptic spreadimpulses, agonists & antagonists recruited - spasms


25/315


26/315

Loss of inhibition of preganglionic sym neurons sympathethyperactivity


27/315

Diagnosis

1. Clinical Observation - based entirely on clinical findings

a. Assess patient physicallyb. Assess for the presence of lockjaw

c. If lockjaw is positive, a logical question would beDo you have a

wound?

2. Examine all cases with wound infection & muscle stiffness

3. Wound cultures in suspected cases, C. tetani can be isolated from wpts without tetanus & frequently cannot be isolated from wounds of thotetanus. If there is afresh wound, microorganisms are still present ther4. Electromyograms continous discharge of motor units, shortening / silent interval seen after AP.

5. Muscle enzymes raised


28/315

SIGNS & SYMPTOMS

1. Spinal Cord

a. Striated musclesLockjaw

b. Trigeminal nervesTrismus

c. Facial nervesRisus Sardonicus

d. Spinal nerves - Opisthotonus

2. Brain

Respiratory Center Pharyngeal SpasmAbdominalGeneral Rigidity (Tonic)


29/315

TYPES OF TETANUS

Traumatic

Puerperal

Otogenic

Idiopathic

Tetanus neonatorum

Generalized

Neonatal

Local


30/315

Clinical Features

May begin from 2 days to several weeks after the injury UWEEK

Remember

Shorter the incubation period

More severe the attack

Worse the prognosis


31/315

Clinical features

GENERALIZED TETANUS

Most common

Increased muscle tone & generalized spasms

Median time of onset after injury7 days

Pt 1st notices increased tone in masseter ( Trismus, lock jaw

Dysphagia Stiffness / pain in neck, shoulder, back muscles appear conc

or soon thereafter

Rigid abd & stiff prox.limb muscles . Hands, feet spared.


32/315

trismus


33/315

Risus Sardonicus : Spasm of facial muscles ( frontalis & angl

mouth muscles ) producing grinning facies Opisthotonus : Painful spasms of neck, trunk and extremity

producing characteristic bowingand arching of back Some pts devolep paroxysmal, violent, painful, generalized

spasms cyanosis . Spasms occur repetitively & may be spo

/provoked by slightest stimulation. Constant threat during general spasm is reduced ventilation

laryngospasm.


34/315

Risus sardonicus


35/315


36/315


37/315

Mild ds ( muscle rigidity , no / few spasms )

Moderate ds (trismus, dysphagia, rigidity, spasm)

Severe ds ( freq explosive paroxysms )

Autonomic dysfn complicates severe cases - labile htn,hyperpyrexia, profuse sweating, peripheral vasoconstriction

catecholamines.


38/315

Neonatal Tetanus

Usually fatal if untreated

Children born to inadequately immunized mothers, after untreatment of umbilical stump

During first 2 weeks of life.

Poor feeding ,rigidity and spasms


39/315


40/315


41/315

Local Tetanus

Uncommon form

Manifestations are restricted to muscles near the wound.

Cramping and twisting in skeletal muscles surrounding the w

local rigidity

Prognosis excellent


42/315

Cephalic Tetanus

A rare form of local tetanus

Follows head injury / ear infection

Involves one / more facial cranial nerves

Trismus and localised paralysis, usually facial nerve, oftenunilateral.

Incubation period : few days Mortality : high


43/315


44/315

Diagnosis

1. Clinical Observation - based entirely on clinical findings

a. Assess patient physicallyb. Assess for the presence of lockjaw

c. If lockjaw is positive, a logical question would beDo you have a

wound?

2. Examine all cases with wound infection & muscle stiffness

3. Wound cultures in suspected cases, C. tetani can be isolated from w

pts without tetanus & frequently cannot be isolated from wounds of thotetanus. If there is afresh wound, microorganisms are still present ther4. Electromyograms continous discharge of motor units, shortening / silent interval seen after AP.

5. Muscle enzymes raised


45/315

Serum Anti toxin levels >= 0.1 IU/ml protective & makes te

unlikely .

H MANAGEMENT


46/315

H. MANAGEMENT1. Prevention

1.1 Active Immunization with tetanus toxoid (TT)6 weeks after birth (togethDiphtheria and Pertussis/DPT): 0.5 ml for 3 doses (4-8 weeks interval)

DPT Immunization for Pregnant Individuals

Dose: 0.5 ml

Route: Intramuscular

Number of Doses given:a. Two (2) doses with three (3) booster doses or;

b. Two (2) doses with booster dose given every pregnancy

When given:a. 1st Dose: Anytime during second trimester of pregnancyb. 2nd Dose: With one (1) month interval

c. Booster Dose: Given with successive pregnancy/ies

H MANAGEMENT


47/315

H. MANAGEMENT

1. Prevention

1.2 Tetanus Toxoid for non-pregnant women 1st Dose (TT1) given anytime0.5 m

2nd Dose (TT2) after 1 month

3rd Dose (TT3) after 6 months

4th Dose (TT4) after 1 year 5th Dose (TT5) after another year

Booster Dose given after 10 years

CO C


48/315

CONCEPT

Succeeding doses of Tetanus Toxoid are given based on DA

LAST DOSE

If a person is high-risk, give booster dose every five (5) yea

If a person is low risk, give booster dose every ten (10) year

Effect of TT administration on the mother

Slight soreness or heaviness on site of injection

H MANAGEMENT


49/315

H. MANAGEMENT

1. Prevention

1.3 Antitoxin is used for the treatment of clinical tetanus an

passive immunization or prophylaxis in recently woun

individuals never previously immunized with tetanus to

P ti A ti I i ti


50/315

Prevention Active Immunization

For partially immunized, unimmunized and recovering from It stimulates production of protective antitoxin

2 prep : combined vaccine : DPT

monovalent vaccine : plain / formol

toxoid

tetanus vaccine , adsorbed

H MANAGEMENT


51/315

H. MANAGEMENT

2. Control

2.1 Medical Aseptic technique

2.2 Concurrent Disinfection (all materials contaminated with

secretions should be securely wrapped in paper and burned AS

Terminal Disinfection (walls and furniture washed with soap

water, room thoroughly aired, mattress and pillows autoclavedaired/sunned for 6-8 hours)

CONCEPT ON WOUND CARE


52/315

CONCEPT ON WOUND CARE

Wash wound with soap and running water

Place antiseptic solution on wound

Use thin dressing

Band Aid Plastic Strips are allowable as they have air ve

holes

Do not use plasterUse only those types of plasters with air ventilation holes

introduce oxygen to the wound

H MANAGEMENT


53/315

H. MANAGEMENT3. Treatment

3.1 Medical Careobjectives are:a. Neutralize the toxintop priority since the toxin is responsible for the S/Sx of

and the systemic infection

(1) Give anti-tetanus serum (ATS) ortetanus anti-toxin (TAT)

Comes from a horse serum Do SKIN TESTING first

If (-) for skin test, inject TIG 0.01 ml in 0.09 ml NSS. Epinephrine or sterocounteract prophylaxis

(2) If (+) for skin testing, DO NOT GIVE the drug

Resort to human serumtetanus immunoglobulin (TIG)

a) Give skin test first: anti-tetanus serum (ATS)b) If skin test is negative, inject Tetanus Anti-Toxin (TAT) 0.01 ml in 0.0

Epinephrine or steroid is given to counteract prophylaxis.

CONCEPT


54/315

CONCEPT

In the Philippine setting, the horse serum is given despite a (+) s

This is done by giving fractional doses.

Example: Initial administration of 0.01 of drug and 0.099 PNSS After 30 minutes, 0.05 of the drug and 0.95 of PNSS

After another 30 minutes, another increase in the dose of the druWhen administering tetanus horse serum, always have ready the

a. EPINEPHRINE

b. CORTICOSTEROID These would be necessary to counteract any delayed reaction, which ma

hypersensitivity reactions leading to anaphylaxis and eventually the deapatient.


55/315

NEUTRALIZE TOXIN :

Inj. Human Tetanus Immunoglobulin (TIG) 3000 6000 units IM, usuadivided doses as volume is large.

ANTIBIOTIC THERAPY :

Although of unproven value , antibiotics adm to eradicate vegetative csource of toxin

IV Penicillin 10 -12 million units daily for 10 days

IV Metronidazole 500mg Q 6 hrly / 1gm Q 12 hrly

Allergic to Penicillin : consider Clindamycin & Erythromycin

H MANAGEMENT


56/315

H. MANAGEMENT

b. Kill the microorganism

(1) Give IV Penicillin (drug of choice): antibiotic to kill the bacter(eradicate vegetative cells) & is given 1 hour before meals or 2meals for bioavailability. If allergic to penicillin, considerClin& Erythromycin

(2) On the fresh wound, do daily cleansing with the use of hydrogeperoxide.

(3) Then apply antiseptic solution like Betadine or Povidone(4) Then cover wound with THIN DRESSING to allow air to circu

through the wound(5) It may also be good to expose the wound but avoid contact wit

H MANAGEMENT


57/315

H. MANAGEMENT

c. Prevent and control spasms

(1) Muscle relaxants

Given during acute phase of tetanus; done via the IV route

methocarbamol (Robaxin, Robaxisal), Lionesal (Baclofen), Eperis

(Myonal)

May be given per orem when the patient is on his way to recover

(2) Sedatives

Valium (diazepam); use IV push or IV drip Concept: I.V. drip regulation is titrated based on the frequenc

spasm

The more frequent the spasm, the faster the rate of the titr

(3) Tranquilizers Thorazine


58/315

(4) Continued spasms : intubate & ventilate

(5) Proceed with other supportive managementa. For urinary retention, do catheterization

b. For constipation, administer laxatives as ordered.

CONCEPT: Stimuli triggers spasm


59/315

CONCEPT: Stimuli triggers spasm

Types of Stimuli:

(1) Exteroceptive Stimuli

Comes from outside environment of the patient Examples: bright light and noise

Place the patient in dim and quiet environment

(2) Interoceptive Stimuli

Comes from inside or within the patient Examples: stress, pain, coughing, passage of flatus(3) Proprioceptive Stimuli

There is participation of the patient and other people Examples: touching, turning, jarring the bed of the patient

H MANAGEMENT


60/315

H. MANAGEMENT3.2 Nursing Caredone to prevent patient from having spasms

a. Place the patient should be in a quiet, darkened/dimmed, wel

ventilated, and non-stimulating environment CONCEPT: Patients are isolated so as not to be exposed to stimuli.

b. Practice Minimal/gentle handling of patient. Touching and Turning is not contraindicated

However, do these as gently as possible Inform the patient before proceeding with any procedure

c. Practice Cluster Care Do all nursing activities in one setting Proper scheduling of nursing care activities so as not to disturb patient o

cleansing bath with warm water, change position, oral hygiene

Do other nursing care activities with vital signs taking

H MANAGEMENT


61/315

H. MANAGEMENT

3.2 Nursing Care

d. Liquid diet of 3,000-4,000 calories via tube feedings as ine. Prevent injury

(1) Do not leave patient alone

(2) Siderails of bed always raised

(3) Padded tongue blades or metal spoon to guard against re

obstruction

e. Proper wound carewash with flowing water, then rinse w

antiseptic solution and cover with thin dressing

Treatment general measures


62/315

Treatment general measures

Goal is to eliminate the source of toxin, neutralize the unbo

& prevent muscle spasm & providing support - resp suppor Admit in a quiet room in ICU

Continuous careful observation & cardiopulmonary monitor

Minimize stimulation

Protect airway Explore woundsdebridement

Management of autonomic dysfn


63/315

Management of autonomic dysfn

Labetalol

Continuous infusion of esmolol

Clonidine / verapamil

Additional measures


64/315

Additional measures

Pts recovering from tetanus should be actively immunized

Hydration

Nutrition

Physiotherapy

Prophylactic anticoagulation

Bowel, bladder, back care Treatment of intercurrent infection

DPT (Diphtheria Pertussis Tetanus)


65/315

VaccineWhen given:

1st Dose: 6 weeks after birth; 0.5 ml

2nd Dose: 10 weeks after birth; 0.5 ml

3rd Dose: 14 weeks after birth; 0.5 ml

Number of Doses: three (3)

Interval between Doses: Four (4) weeksAdministration Site: Vastus lateralis muscle

Route: Intramuscular

IMPORTANT CONCEPTS IN DPTADMINISTRATION


66/315

ADMINISTRATIONa. Expect fever to set in after administration of DPT vaccine

Give paracetamol

Apply warm compress for better drug absorption Immediately follow up with cold compress to avoid soreness

b. If tenderness or swelling on site of injection is present:

Do cold compress within twenty-four (24) hours

Then do warm compress

c. Observe for signs of convulsions within seven (7) days after DPT immun

This indicates that child has reaction with the pertussis component of the dru Therefore, succeeding doses of DPT will NOT BE GIVEN

Give ONLY the DT components

If DPT is given again, this predisposes the child to neurologic disorders

d. Observe if child cries uncontrollably

IMPORTANT CONCEPTS IN DPTADMINISTRATION


67/315

ADMINISTRATION

d. Observe if child cries uncontrollably

This is an indication of development of neurologic disorder

Monovalent vaccines


68/315

Monovalent vaccines

Purified tetanus toxoid ( adsorbed ) supplanted the palin tox

higher & long lasting immunity response Primary course of immunization 2 doses

Each 0.5 ml , injected into arm given at intervals of 1-2 mon

The longer the interval b/w two doses, better is the immune

1st

booster1 yr after the initial 2 doses 2nd Booster : 5 yrs after the 1st booster ( optional )

Freq boosters to be avoided

Passive immunization


69/315


Temp protection human tetanus immunoglobulin /ATS

Human Tetanus Hyperimmunoglobulin :

250-500 IU

Does not cause serum sickness

Longer passive protection compared to horse ATS( 30 days /

days )



70/315


ATS ( EQUINE ) :

1500 IU s/c after sensitivity testing

7 10 days

High risk of serum sickness

It stimulates formation of antibodies to it , hence a person w

once received ATS tends to rapidly eliminate subsequent do

Active & Passive Immunization


71/315

Active & Passive Immunization

In non immunized persons

1500 IU of ATS / 250-500 units of Human Ig in one arm & 0.adsorbed tetanus toxoid into other arm /gluteal region

6 wks later, 0.5 ml of tetanus toxoid

1 yr later , 0.5 ml of tetanus toxoid

Prevention of neonatal tetanus


72/315

Clean delivery practices

3 cleans : clean hands, clean delivery surface, clean cord car Tetanus toxoid protects both mother & child

Unimmunized pregnant women : 2 doses tetanus toxoid

1st dose as early as possible during pregnancy

2nd

dose at least a month later / 3 wks before delivery


73/315

Immunized pregnant women : a booster is sufficient

No need of booster in every consecutive pregnancy

Prevention of tetanus after injury


74/315

j y

All wounds should be thoroughly cleaned soon after injury

Remove all foreign bodies, soil, dust, necrotic tissueA completed course of toxoid/booster < 5 yrs ago

B- completed course of toxoid / booster >5 yrs ago & < 10 y

C- completed course of toxoid / booster >10 yrs ago

D- not completed course of toxoid / immunity status unkno

Wounds < 6hrs, clean, non penetrating negligible tissue damage


75/315

negligible tissue damage

Immunity Category

A

B

C D

Treatment

Nothing more required

Toxoid 1 dose

Toxoid 1 dose Toxoid complete cours

Other Wounds


76/315

Immunity Category

A

B

C

D

Treatment

Nothing more required

Toxoid 1 dose

Toxoid 1 dose + HumanIg

Toxoid complete coursHuman Tetanus Ig


77/315

MENINGITIS


78/315


79/315

MENINGITISMeningitis is an inflammatory process of the leptomeninges and

Space occupying lesions


80/315

CNS hemorrhage

Brain tumours Brain abscess

Metastatic tumours

Classification


81/315

1. acute pyogenic (bacterial) meningitis

2.acute aseptic (viral) meningitis 3.acute focal suppurative infection (brain abscess,subdural a

extradural empyema)

4.chronic bacterial infection (tuberculosis).

Acute pyogenic bacterial meningitis


82/315

Most important

Can be fatal if untreated Organisms:

E.coli ---------- neonates

Streptococci B ---------- neonantes

H. influenzae-------------adolescents

Neisseria meningitidis------------- young adults

Streptococcus pneumonia--------- elderly

Clinical signs


83/315

Signs of infection (fever,malaise,rigor.)

Signs of meningeal irritation:

1.headache

2.neck stiffness

3.photophobia

4.irritability

C.S.F by lumbar puncture shows :

a.cloudy purulent csfb.abundant neutrophils > 90,000/mm3

c.high protein level and

d.reduced glucose level.

Morphology


84/315

Grossly , pyogenic meningitis shows a thick layer of suppura

exudate covers the leptomeninges over the surface of the b Exudate in basal surface--- H.INFLUENZAE

Exudate in covexity surface--- P.MENINGT

Microscopically :

neutrophils in the subarachnoid space


85/315


86/315


87/315


88/315


89/315


90/315

Complications


91/315

Antibiotic treatment------ full recovery

Delayed or untreated cases--- can be fatal Healing by fibrosis cause obliteration of subarachenoid spac

HYDROCEPHALUS

Brain abscess

Septic shock and skin rashes, why ?

Skin rashes


92/315

Is due to small skin bleed

All parts of the body are affeced

The rashes do not fade under pressure Pathogenesis:

a. Septicemia

b. wide spread endothelial damage

c. activation of coagulation

d. thrombosis and platelets aggregation

e. reduction of platelets (cosumption )f. BLEEDING 1.skin rashes

2.adrenal hemorrhage

Arenal hemorrhage is called Waterhouse-Friderichsen Syndrome.It cause acute adrinsufficiency and is uaually fatal


93/315


94/315

Acute Aseptic (Viral ) Meningitis


95/315

Can follow any viral infection

Less danger CSF shows :

1.lymphocytes

2. mild increase in protein

3. normal glucose level

Viral meningitis is usually self-limiting and treated symptoma

Brain abscess


96/315

Causes :

1. complication of bacterial meningitis2. bacterial endocarditis

3. pulmonary sepsis : peumoniaetc

4. other sepsis

Brain abscess cause a space occupying lesion in the brain


97/315


98/315

Neisseria meningitidis

(meningococcus)


99/315

MENINGOCOCCEMIA

Encapsulated small, gram-negative diplococci

Second most common cause (behind S. pneumonia

it i d i iti i i l h lth

General Overview of Neisseria meningitidis


100/315

community-acquired meningitis in previously health

adults; swift progression from good health to life-

threatening disease Pathogenicity:

Pili-mediated, receptor-specific colonization of

nonciliated cells of nasopharynx

Antiphagocytic polysaccharide capsule allows

systemic spread in absence of specific immunity Toxic effects mediated by hyperproduction of

lipooligosaccharide

Serogroups A, B, C, Y, W135 account for about 90%

all infections

Diseases Associated with Neisseriameningitidis


101/315

Following dissemination of virulent

organisms from the nasopharynx: Meningitis

Septicemia (meningococcemia) with or with

meningitis

Meningoencephalitis

Pneumonia

Arthritis

Urethritis

Neisseria meningitidis inCerebrospinal Fluid


102/315

Humans only natural hosts

Person-to-person transmission by aerosolizatio

respiratory tract secretions in crowded condition

Epidemiology of Meningococcal Disease


103/315

respiratory tract secretions in crowded condition

Close contact with infectious person (e.g., famil

members, day care centers, military barracks,prisons, and other institutional settings)

Highest incidence in children younger than 5 ye

and particularly those younger than 1 year of ag

passive maternal antibody declines and as infan

immune system matures Commonly colonize nasopharynx of healthy

individuals; highest oral and nasopharyngeal

carriage rates in school-age children, young ad

and lower socioeconomic groups

Age Distribution of Meningococcal Dise

in USA

Lacking maternal antibody


104/315

Specific receptors (GD1 ganglioside) for bacterial fimbri

nonciliated columnar epithelial cells in nasopharynx of h

O

Pathogenesis of Meningococcal Disease


105/315

Organisms are internalized into phagocytic vacuoles, av

intracellular killing in absence of humoral immunity and

complement system (patients with late complementdeficiencies are particularly at risk)

Replicate intracellularly and migrate to subepithelial spa

where excess membrane fragments are released

Hyperproduction of endotoxin (lipid A of LOS) and blebb

into surrounding environment (e.g., subepithelial spacesbloodstream) mediates most clinical manifestations inclu

diffuse vascular damage (e.g., endothelial damage, vas

(inflammation of vessel walls), thrombosis (clotting),

disseminated intravascular coagulation (DIC)

Skin Lesions of Meningococcemia


106/315

NOTE:Petechiaehave coalesced into

hemorrhagic bullae.

Following colonization of the nasopharynx, prote

humoral immunity develops against the same or

Immunogenicity of Neisseria meningitidis


107/315

humoral immunity develops against the same or

closely related organisms of the same serogroup

not against other serogroupsBactericidal activity of the complement system is

required for clearance of the organisms

Cross-reactive protective immunity acquired with

colonization by closely related antigenic strains a

with normal flora of other genera (e.g., E. coliK1progressive disease can occur in absence of

serogroup-specific immunity

Large numbers (e.g., >107cells/ml) of encapsula

Laboratory Characterization of Neisseria meningitidis


108/315

g ( g , ) p

small, gram-negative diplococci (flattened along

adjoining side) and polymorphonuclear leukocy(PMNs) can be seen microscopically in

cerebrospinal fluid (CSF)

Transparent, non-pigmented nonhemolytic colo

on chocolate blood agar with enhanced growth

moist atmosphere with 5% CO2 Oxidase-positive

Acid production from glucose and maltose but n

from other sugars

Prevention and Treatment of Meningococcal Disease

Penicillin is drug of choice for treatment in adjunct

supportive therapy for meningeal symptoms


109/315

Increasing MIC mediated by genetic alteration o

target penicillin binding proteins is being monito

Chloramphenicol or cephalosporins as alternati

Chemoprophylaxis of close contacts with rifampin

sulfadiazine (if susceptible)

Polyvalent vaccine containing serogroups A, C, Y,

W135 is effective in people older than 2 years of a

for immunoprophylaxis as an adjunct tochemoprophylaxis

Serogroup B is only weakly immunogenic and

protection must be acquired naturally from expo

to cross-reacting antigens


110/315

VIRAL ENCEPHALITIS


111/315

Introduction


112/315

Encephalitis is an acute inflammatory process affecting the brain

Viral infection is the most common and important cause, with over 10

implicated worldwide

Symptoms Fever

Headache

Behavioral changes

Altered level of consciousness

Focal neurologic deficits

Seizures

Incidence of 3.5-7.4 per 100,000 persons per year

Causes of Viral Encephalitis

H i HSV 1 HSV 2 i ll t i t l i E t i B


113/315

Herpes viruses HSV-1, HSV-2, varicella zoster virus, cytomegalovirus, Epstein-Barr herpes virus 6

Adenoviruses

Influenza A

Enteroviruses, poliovirus

Measles, mumps, and rubella viruses

Rabies

Arboviruses examples: Japanese encephalitis; St. Louis encephalitis virus; West Nivirus; Eastern, Western and Venzuelan equine encephalitis virus; tick borne enceph

Bunyaviruses examples: La Crosse strain of California virus

Reoviruses example: Colorado tick fever virus

Arenaviruses example: lymphocytic choriomeningitis virus

What Is An Arbovirus?

A b i h d b i


114/315

Arboviruses = arthropod-borne viruses

Arboviruses are maintained in nature through biological trabetween susceptible vertebrate hosts by blood-feeding arth

Vertebrate infection occurs when the infected arthropod takblood meal


115/315

http://www.cdc.gov/ncidod/dvbid/arbo

Major Arboviruses That Cause Encepha

Fl i i id


116/315

Flaviviridae Japanese encephalitis

St. Louis encephalitis

West Nile

Togaviridae Eastern equine encephalitis

Western equine encephalitis

Bunyaviridae La Crosse encephalitis


117/315


118/315

West Nile Virus

West Nile Virus

Flavivirus


119/315

Primary host wild birds

Principal arthropod vectormosquitoes

Geographic distribution - Africa,Middle East, Western Asia,Europe, Australia, North America,

Central America

http://www.walgreens.com/images/library/healtht

History of West Nile Virus

1937 West Nile virus isolated from woman in Uganda


120/315

1937 - West Nile virus isolated from woman in Uganda

1950s First recorded epidemics in Israel (1951-1954, 1957

1962 Epidemic in France

1974 Epidemic in South Africa. Largest ever West Nile epi

1996 Romanian epidemic with features similar to those ofAmerican outbreak. 500 cases and 50 deaths.

1999 Russian outbreak. 40 deaths.

West Nile Virus: 1999 New York Outbrea

Crows dying in and around Queens in latesummer


121/315

summer

27 deaths among captive birds in the Queens

and Bronx zoos Concomitant human infection of apparent

encephalitis in the same area

Outbreak was first attributed to St. Louisencephalitis, but tissue samples from deadcrows confirmed that it was West Nile virus

59 human cases requiring hospitalization,including 7 deaths

Spread of West Nile Virus in the US

2000 spread throughout New England andMid-Atlantic regions.


122/315

g

18 new human cases reported

2001 spread throughout the entire easternhalf of the US

64 cases reported, with NY, FL and NJaccounting for 60%

2002 spread westward across Great Plainsinto Western US. Reached California by LaborDay.

By end of 2002 cumulative human cases > 3900,with > 250 deaths

2003 US, Canada, Mexico 9,858 cases reported to CDC, including 262

deaths in 45 states and D.C.

West Nile Activity in the US Reports aApril 7, 2004


123/315

West Nile Activity in the US CountiesReporting Cases as of March 24, 2004


124/315

West Nile Virus 2004:BREAKING NEWS

April 13, 2004 Ohio may have first 2004 West Nile Case 79 year old man from Scioto County OH was admitted April 1 with v


125/315

79 year old man from Scioto County, OH was admitted April 1 with vmeningitis and encephalitis which rapidly progressed to coma over 2

days. Initial IgM antibody titers were positive for West Nile virus and he

complained of itching from insect bites upon admission

Has been treated with blood-pressure drugs to control over-responsby the immune system to West Nile virus, causing brain inflammatio

Previously unresponsive and paralyzed.

Can now open his eyes and shake his head in response to questions, bstill cannot talk.


126/315

St. Louis Encephalitis


Flavivirus


127/315

Most common mosquito-

transmitted human pathogen inthe US

Leading cause of epidemicflaviviral encephalitis

History of St. Louis Encephalitis

1933 virus isolated during St. Louis and Kansas City, MO ep


128/315

g y, p

1940s virus spread to Pacific Coast

1959-1971 virus spread to Southern Florida

1974-1977 last major epidemic. Over 2,500 cases in 35 st

1990-1991 South Florida epidemic. 226 cases and 11 dea

1999 New Orleans outbreak. 20 reported cases.



129/315


130/315

Japanese Encephalitis

Japanese Encephalitis

Flavivirus related to St. Louis encephalitis

Most important cause of arboviral encephalitis


131/315

Most important cause of arboviral encephalitisworldwide, with over 45,000 cases reported

annually Transmitted by culex mosquito, which breeds in

rice fields

Mosquitoes become infected by feeding ondomestic pigs and wild birds infected withJapanese encephalitis virus. Infectedmosquitoes transmit virus to humans andanimals during the feeding process.

History of Japanese Encephalitis

1800s recognized in Japan


132/315

1924 Japan epidemic. 6125 cases, 3797 deaths

1935 virus isolated in brain of Japanese patient who died encephalitis

1938 virus isolated from Culex mosquitoes in Japan

1948 Japan outbreak

1949 Korea outbreak

1966 China outbreak Today extremely prevalent in South East Asia. 30,000-50,0reported each year.

Distribution of Japanese Encephalitis in1970-1998


133/315

Eastern Equine


134/315

Eastern Equine

Encephalitis

Eastern Equine Encephalitis

Togavirus

Caused by a virus transmitted to humans and


135/315

horses by the bite of an infected mosquito.

200 confirmed cases in the US 1964-present Average of 4 cases per year

States with largest number of cases Florida,Georgia, Massachusetts, and New Jersey.

Human cases occur relatively infrequently,largely because the primary transmission cycle

takes place in swamp areas where populationstend to be limited.

History of Eastern Equine Encephalitis

1831 First recognized as a disease in horses. Over 75 hors3 i i M h


136/315

3 counties in Massachusetts.

1845-1912 epizootics in Northeast and Mid-Atlantic region

1933 virus isolated from horse brains

1938 association of human disease with epizootics. 30 caencephalitis in children living in same area as equine cases.

1947 largest recorded outbreak in Louisiana and Texas. 13cases and 11,722 horse deaths


137/315

Western Equine


138/315

Western Equine

Encephalitis

Western Equine Encephalitis

Togavirus

Mosquito-borne


139/315

Mosquito borne

639 confirmed cases in the USsince 1964

Important cause of encephalitis inhorses and humans in NorthAmerica, mainly in the Western

parts of the US and Canada

History of Western Equine Encephalitis

Early 1900s epizootics of viral encephalitis in horses descrArgentina


140/315

Argentina

1912 25,000 horses died in Central Plains of US

1930 San Joaquin Valley, CA outbreak. 6000 cases in horseisolated from horse brains

1938 virus isolated from brain of a child


141/315


142/315

La Crosse Encephalitis

La Crosse Encephalitis Bunyavirus

On average 75 cases per year reported to the CDC

Most cases occur in children under 16 years old


143/315

Most cases occur in children under 16 years old

Zoonotic pathogen that cycles between the daytimebiting treehole mosquito, and vertebrate amplifierhosts (chipmunk, tree squirrel) in deciduous foresthabitats

Most cases occur in the upper Midwestern state, butrecently cases have been reported in the Mid-Atlantic region and the Southeast

1963 isolated in La Crosse, WI from the brain of achild who died from encephalitis


144/315

Summary Confirmed and Probable Human in the US

Virus Years Total cases


145/315

Eastern Equine 1964-2000 182

Western Equine 1964-2000 649

La Crosse 1964-2000 2,776

St. Louis 1964-2000 4,482

West Nile 1999-present > 9,800

Molecular Biology of Virusethat can Cause Viral


146/315

that can Cause Viral

Encephalitis Flaviviridae: West Nile Virus

Togaviridae: Eastern and Western EquiEncephalitis

Bunyaviridae: La Crosse Virus

Flavivirus


147/315

Flavivirus Japanese Encephalitis Virus

St. Louis encephalitis virus

West Nile Virus

Flavivirus: Virus Classification

Family Flaviviridae

3 G


148/315

3 Genera Flavivirus, Pestivirus, Hepacivirus

Flavivirus - 12 Serogroups Japanese encephalitis virus serogroup

Includes West Nile Virus (WNV), St. Louis Encephalitis, and othe

Scanned images of West Nile virus isolated from tissue from a crow found in New York.


149/315

Viral Replication Cycle
http://arjournals.annualreviews.org/na101/home/literatum/ar/journals/production/micro/2002/56/1/annurev.micro.56.012302.160654/images/large/mi56_0371_2.jpeg


150/315

Genome Structure
http://arjournals.annualreviews.org/na101/home/literatum/ar/journals/production/micro/2002/56/1/annurev.micro.56.012302.160654/images/large/mi56_0371_2.jpeghttp://arjournals.annualreviews.org/na101/home/literatum/ar/journals/production/micro/2002/56/1/annurev.micro.56.012302.160654/images/large/mi56_0371_1.jpeg


151/315

Viral Genome

Positive Strand RNA Genome

1 ORF Genome encodes single polyprotein which is subseq
http://arjournals.annualreviews.org/na101/home/literatum/ar/journals/production/micro/2002/56/1/annurev.micro.56.012302.160654/images/large/mi56_0371_1.jpeg


152/315

1 ORF Genome encodes single polyprotein which is subseq

cleaved 5 portion

3 structural proteins

3 portion 7 non-structural proteins

Genome also includes 5 and 3 noncoding regions which hafunctional importance

Secondary structure loops


153/315

3 Stem Loop of Plus Strand

Tertiary interactions of 3 non-coding region serve to stabilizcompact the 3 region of the genome and may also create b


154/315

sites for cellular and/or viral proteins PseudoknotsFormed by interactions between 3 stem loo

adjacent nucleotides

PK1 May be important for minus strand replication

Interacts with cellular proteins

P104, EF-1, and p84

Conserved Secondary and TertiaryTerminal RNA Structures in MinusStrand

Stem loop structures at 5 and 3 ends are conserved


155/315

Stem loop structures at 5 and 3 ends are conserved

across flavivirus species suggesting a functionalimportance for these groups.

Minus strand stem loops may play a role in facilitatinthe formation of replication complexes and inreleasing newly synthesized minus strands from plus

strands. In addition, its interaction with cellular proteins is

important for replication.

Viral Proteins: Structural and Non-Structural Structural Proteins

Capsid (C), Membrane (M), Envelope (E)


156/315

The envelope - receptor binding Dimers of E protein arrange their sheets in a head to tail formati

flat on top of the lipid bilayer. The distal portions of these proteinanchored in the membrane

Non-Structural Multifunctional Proteins NS1, NS2A, NS2B, NS3, NS4A, NS4B, NS5

Many functions of non-structural proteins have yet to be de

Viral Non-Structural Proteins

NS1- may play a role in flavivirus RNA synthesis; it has been shown to be essential fostrand synthesis

NS2A NS2B NS4A NS4B - may facilitate the assembly of viral replication complexes


157/315

NS2A, NS2B, NS4A, NS4B - may facilitate the assembly of viral replication complexes

unknown mechanism NS3: Multifunctional

Proteolytic function upon association with NS2B

RNA triphosphatase function thought to be important for the synthesis of the 5

Helicase and NTPase activity

Its activity may be upregulated through interaction with phosphorylated NS5

NS5 RNA dependent RNA polymerase

Methyltransferase domain thought to be required for formation of the 5 cap

Model for Closed-Loop Complex FormaFlaviviruses


158/315


159/315

Togavirus Eastern Equine Encephalitis Virus

Western Equine Encephalitis Virus

Venezuelan Equine Encephalitis Virus

Togavirus

Family: Togaviridae Genus: Alphavirus


160/315

49S Single Stranded Genome ~11700 Nucleotides

3 end: Five potential structural proteins C, E3, E2, 6K, and E1

5 end: Unknown number of non-structural proteins probab

involved in replication Genome has an opposite orientation from the Flaviviruses

Alphavirus Structure


161/315

http://www.cdc.gov/ncidod/dvbid/arbor/alphavir.htm

Alphaviruses: Protein Function

E1and E2 glycoprotein heterodimers form trimers that appear as knobsurface of the virion

E1 transmembrane glycoprotein with 2 to 3 N-linked glycosylation sites


162/315

E2 - glycoprotein with 1 to 2 N-linked glycosylation sites, contains short intracyand hydrophobic stretch of amino acids that serves as the fusion peptide for vir

Capsid protein has a conserved N-terminal region which binds RNA anterminal region which interacts with the cytoplasmic tail of E2 as well proteins

E3 and 6K proteins are signal sequences for E2 and E1, respectively, anlargely cleaved off from the mature virion

Replication Cycle

Proposed Model: E1 glycoprotein interacts with proteins on the cell subinds to cellular proteins and receptor-mediated endocytosis takes pl

In acidified endosomal compartment glycoproteins fuse with membra


163/315

In acidified endosomal compartment, glycoproteins fuse with membranucleocapsid is released.

Virion RNA serves as mRNA, translation of non-structural proteins beg

Structural proteins are transcribed as polyprotein

E2 and E1 travel from ER to the Golgi

At cellular membrane regions containing E1 and E2 heterodimers intenucleocapsids and viral particles bud from the cell surface


164/315

BunyaviridaeLa Crosse Virus

La Crosse Virus
http://www.wadsworth.org/databank/lacrosse.htm/


165/315

http://www.virology.net/Big_Virology/BVRN

Bunyaviruses

Genome - single strand of negative sense RNA

Four structural proteins
http://www.wadsworth.org/databank/lacrosse.htm/


166/315

Two external proteins Two associated with RNA to form nucleocapsid

Matrix proteins absent from Bunyaviruses, therefore capsid and envelope glycoproteins directly interact prior to buddin

Bioweaponization


167/315

http://www.cdc.gov/ncidod/dvbid/arbor/index.htm

Mosquito vector

T

ransmission Cycle is Key to

Weaponization

Incidental infection


168/315

West Nile virus

Bird reservoir hosts Incidental infections

http://www.cdc.gov/ncidod/dvbid/westnile/conf/February_20

Bioweaponization

Vector, Vector, Vector In areas around NYC mosquitoes are extremely ubiquitous during

months


169/315

months

Mosquitoes are already virulent, further genetic engineeringunnecessary

A fully effective cure is not available

Diagnosis is difficult

Widespread Panic would be generated as the outbreak prog

The Iraq Connection

The US shipped various pathogens, including WNV, to Iraq in1980s


170/315

In 1999 following the West Nile Virus outbreak in NYC therefears that Iraqi bioterrorism was involved

Investigations by the CDC and the CIA found no evidence ofbioterrorism in the 1999 outbreak

WNV as a low-tech Bioweapon:Possible Connection to 1999 outbreak

Gather mosquitoes in an endemic area

Incubate mosquitoes with a food source


171/315

Put them to sleep Place mosquitoes in a matchbox

Board plane to US

Take bus from airport; Release mosquitoes from buswindow

Wait for outbreak

Source: Dr. Ilya Tr


172/315

Clinical Considerations

Case Study

In August 2002, a 91 year old male from Northern Staten Island who pinitially with sudden onset of fever, left lower extremity weakness, inawalk, and possibly some transient and mild AMS, was admitted to a Sthospital.


173/315

hospital.

He was not considered to have aseptic meningitis or encephalitis and infection was not considered at that time. After being discharged, he evaluated by a neurologist for persistent left leg weakness and inabilit

In April 2003, the neurologist reported this case to the DOHMH as a ppolio case. Serological specimens were forwarded to the NYSDOH whtested positive for WN virus.


174/315

Clinical ConsiderationsDiagnosis

Patient History

Detailed history critical to determine the likely cause of encephalitis.

Prodromal illness, recent vaccination, development of few days Acute DisseminatEncephalomyelitis (ADEM) .


175/315

Biphasic onset: systemic illness then CNS disease Enterovirus encephalitis. Abrupt onset, rapid progression over few days HSE.

Recent travel and the geographical context: Africa Cerebral malaria

Asia Japanese encephalitis

High risk regions of Europe and USA Lyme disease

Recent animal bites Tick borne encephalitis or Rabies.

Occupation Forest worker, exposed to tick bites

Medical personnel, possible exposure to infectious diseases.

History cont.

Season Japanese encephalitis is more common during the rainy season.

Arbovirus infections are more frequent during summer and fall.


176/315

Predisposing factors: Immunosuppression caused by disease and/or drug treatment.

Organ transplant Opportunistic infections

HIV CNS infections

HSV-2 encephalitis and Cytomegalovirus infection (CMV)

Drug ingestion and/or abuse

Trauma

Initial Signs

Headache

Malaise


177/315

Anorexia Nausea and Vomiting

Abdominal pain

Developing Signs

Altered LOC mild lethargy to deep coma.

AMS confused, delirious, disoriented.


178/315

Mental aberrations: hallucinations agitation personality change behavioral disorders occasionally frank psychosis

Focal or general seizures in >50% severe cases. Severe focused neurologic deficits.

Neurologic Signs

Virtually every possible focal neurological disturbance has breported.


179/315

Most Common Aphasia Ataxia

Hemiparesis with hyperactive tendon reflexes

Involuntary movements

Cranial nerve deficits (ocular palsies, facial weakness)

Other Causes of Encephalopathy

Anoxic/Ischemic conditions

Metabolic disorders

Nutritional deficiency


180/315

Toxic (Accidental & Intentional) Systemic infections

Critical illness

Malignant hypertension

Mitochondrial cytopathy (Reyes and MELAS syndromes)

Hashimotos encephalopathy

Traumatic brain injury Epileptic (non-convulsive status)

CJD (Mad Cow)

Differential Diagnosis

Distinguish Etiology (1) Bacterial infection and other infectious conditions

(2) Parameningeal infections or partially treated bacterial meningitis

(3) Nonviral infectious meningitides where cultures may be negative (e.g., fung


181/315

tuberculous, parasitic, or syphilitic disease) (5) Meningitis secondary to noninfectious inflammatory diseases

MRI Can exclude subdural bleeds, tumor, and sinus thrombosis

Biopsy Reserved for patients who are worsening, have an undiagnosed lesion after sca

response to acyclovir. Clinical signs cannot distinguish different viral encephalitides

Differential Diagnosis cont.

Encephalopathy Encephalitis

Fever Uncommon Common

Headache Uncommon Common


182/315

AMS Steady deterioration May fluctuate

Focal Neurologic Signs Uncommon Common

Types of seizures Generalized Both

Blood: Leukocytosis Uncommon Common

CSF: Pleocytosis Uncommon Common

EEG: Diffuse slowing Common +Focal

MRI Often normal Focal Abn.

Cli i l C id ti


183/315

Clinical ConsiderationsRadiology

MRI


184/315

MRI


185/315

Cli i l C id ti


186/315

Clinical ConsiderationsLaboratory Diagnosis

Laboratory Diagnosis

Diagnosis is usually based on CSF Normal glucose

Absence of bacteria on culture.

Vi i ll i l t d di tl f CSF


187/315

Viruses occasionally isolated directly from CSF Less than half are identified

Polymerase Chain Reaction techniques Detect specific viral DNA in CSF

NYSDOH PCRNEW YORK STATE DEPARTMENT OF HEALTH (NYSDOH)

Viral Encephalitis Letter of Agreement for

Physician Ordered Testing by Polymerase Chain Reaction (PCR)

NYSDOH's Wadsworth Center offers the following tests on CSF for viral encephalitis:

PCR testing for a panel of viruses including: herpes simplex varicella zoster cytomegalovirus( ) ( )


188/315

PCR testing for a panel of viruses, including: herpes simplex, varicella zoster, cytomegalovirus,Epstein-Barr virus, enteroviruses, St. Louis encephalitis (SLE), eastern equine encephalitis (EEE),California encephalitis (including LaCrosse and Jamestown Canyon viruses), Powassan and West N(WN) viruses, and

Enzyme-linked immunoassay (ELISA) for WN virus.

If there is insufficient quantity of CSF (less than 1.0 ml) to conduct both ELISA and PCR for WN virplease consider the following in determining which test is most appropriate for your patient:

ELISA is more sensitive than PCR for WN viral testing and should be considered when there isstronger suspicion of WN virus than other viruses.

PCR is less sensitive for WN virus, but tests for a wide range of viruses. PCR should be considered

viruses other than WN virus are suspected.

Please note your testing priority below or on the viral encephalitis/meningitis case report form. IPCR testing is desired, the agreement below must be completed.

Viral Encephalitis PCR Panel West Nile Virus ELISA Antibody Testing

Cli i l C id ti


189/315

Clinical ConsiderationsDisease Progression

Disease Progression

Worsening neurologic symptoms

Vascular collapse and shock May be due to adrenal insufficiency.


190/315

Loss of tissue fluid may be equally important.

Homeostatic failure

Decreased respiratory drive

Cli i l C id ti


191/315

Clinical ConsiderationsTreatment

Treatment

When HSE cannot be ruled out, Acyclovir must be started p(before the patient lapses into coma) and continued at leastfor maximal therapeutic benefit.

Rocky Mountain spotted fever should also be considered an


192/315

Rocky Mountain spotted fever should also be considered, antreatment with Doxycycline is indicated.

Suspected HSE Treatment Plan


193/315

Acyclovir

Acyclovir is a synthetic purine nucleoside analogue with inhactivity against HSV-1 and HSV-2, varicella-zoster virus (VZVBarr virus (EBV) and cytomegalovirus (CMV)

In order of decreasing effectiveness


194/315

In order of decreasing effectiveness

Highly selective

Acyclovir Action Thymidine Kinase (TK) of uninfected cells does not use acyclovir as a substrate.

TK encoded by HSV, VZV and EBV2 converts acyclovir into acyclovir monophosphate

The monophosphate is further converted into diphosphate by cellular guanylate kintriphosphate by a number of cellular enzymes.

Acyclovir triphosphate interferes with Herpes simplex virus DNA polymerase and inh


195/315

Acyclovir triphosphate interferes with Herpes simplex virus DNA polymerase and inhDNA replication.

Acyclovir triphosphate incorporated into growing chains of DNA by viral DNA polym

When incorporation occurs, the DNA chain is terminated.

Acyclovir is preferentially taken up and selectively converted to the active triphosphHSV-infected cells.

Thus, acyclovir is much less toxic in vitro for normal uninfected cells because: 1) less2) less is converted to the active form.

Supportive Therapy Fever, dehydration, electrolyte imbalances, and convulsions require treatment.

For cerebral edema severe enough to produce herniation, controlled hyperventilatioand dexamethasone.

Patients with cerebral edema must not be overhydrated.

If these measures are used, monitoring ICP should be considered.


196/315

, g If there is evidence of ventricular enlargement, intracranial pressure may be monito

conjunction with CSF drainage.

Outcome is usually poor.

For infants with subdural effusion, repeated daily subdural taps through the sutures usu

No more than 20 mL/day of CSF should be removed from one side to prevent sudden shintracranial contents.

If the effusion persists after 3 to 4 weeks of taps, surgical exploration for possible excisio

membrane is indicated.

Dexamethasone

Synthetic adrenocortical steroid

Potent anti-inflammatory effects

Dexamethasone injection is generally administered initiallyIM


197/315

Dexamethasone injection is generally administered initially IM

Side effects: convulsions; increased ICP after treatment; verheadache; psychic disturbances



198/315

Clinical ConsiderationsPatient Prognosis

Prognosis The mortality rate varies with etiology, and epidemics due to the sam

in severity in different years.

Bad: Eastern equine encephalitis virus infection, nearly 80% of survivors have seneurological sequelae.

Not so Bad: EBV, California encephalitis virus, and Venezuelan equine encephal


199/315

, p , q psevere sequelae are unusual.

Approximately 5 to 15% of children infected with LaCrosse virus have a residuadisorder, and 1% have persistent hemiparesis.

Permanent cerebral sequelae are more likely to occur in infants, but ychildren improve for a longer time than adults with similar infections.

Intellectual impairment, learning disabilities, hearing loss, and other lasting seqbeen reported in some studies.

Prognosis w/ Treatment Considerable variation in the incidence and severity of sequelae.

Hard to assess effects of treatment.

NIAID-CASG trials: The incidence and severity of sequelae were directly related to the age of the patient an

consciousness at the time of initiation of therapy. Patients with severe neurological impairment (Glasgow coma score 6) at initiation of the


200/315

Patients with severe neurological impairment (Glasgow coma score 6) at initiation of thedied or survived with severe sequelae.

Young patients (


201/315

Verbal Incomprehensible words 2

Response Inappropriate words 3

Disoriented conversation 4

Oriented conversation 5

Best None 1

Motor Abnormal extension 2

Response Abnormal flexion 3

Flexion withdrawal 4

Localizes pain 5

______________Obeys commands _________6 _

Total score 3-15



202/315

Clinical ConsiderationsVaccination

Vaccination

None for most Encephalitides

JE Appears to be 91% effective

There is no JE-specific therapy other than supportive care


203/315

p py pp

Live-attenuated vaccine developed and tested in China Appears to be safe and effective

Chinese immunization programs involving millions of children

Vero cell-derived inactivated vaccines have been developed in Chi 2 millions doses are produced annually in China and Japan

Several other JE vaccines under development

Public Health

Considerations


204/315

ConsiderationsEndemic Prevention

Infection Control CDCs Three Ways to Reduce your West Nile Virus Risk

Avoid mosquito bites

Mosquito-proof your home

Help your community


205/315

Avoid Mosquito Bites Apply Insect Repellent Containing DEET

Clothing Can Help Reduce Mosquito Bites Cover up

Be Aware of Peak Mosquito Hours


206/315

Be Aware of Peak Mosquito Hours

Dusk to dawn are peak mosquito biting times for many species.

Mosquito-Proof Home Drain Standing Water

Install or Repair Screens


207/315

Community-Wide Efforts Clean Up Breeding Grounds

Ensure Safe Blood Supply

Mosquito Control Programs

Controversial


208/315

Controversial

Surveillance

Blood Supply NYC Policy Statement reflecting FDA policy:

To reduce WN transmission through blood components. donations will be screened for WN virus RNA using nucleic

amplification tests (NAT). In the event of a NAT-reactive donbl d ll d ll bl d


209/315

blood centers will remove and quarantine all blood componassociated with the donation and notify the state or local hedepartment. In addition, blood testing centers have added questions to identify and exclude persons with fever and he

the week prior to donation.

Mosquito Control ProgramsNYC DOHMH Statement:

We hope that spraying of adulticides will not be required thsummer. However, if there is a threat of an outbreak of hum

and spraying is deemed necessary, targeted adult mosquito ( i d i l i f i id ) b


210/315

measures (via ground or aerial spraying of pesticides) may brequired.

Mosquito Control But wait, theres more:

Same Memo:

Confirmed or suspected cases of pesticide poisoning must breported to the New York State Department of Healths Pest


211/315

p pPoisoning Registry at (800)-322-6850, and to the New York CControl Center at (212)-764-7667.

Whats Being Sprayed The adulticides used during the last three seasons in New Yo

Sumithrin, a pyrethroid.

Although pyrethroids are among the least toxic insecticides,nerve poisons, and act upon the sodium ion channels in ner

membranes.I h li th id i ti id hi h i


212/315

Inhaling pyrethroid insecticides can cause coughing, wheezishortness of breath, runny or stuffy nose, chest pain, or diffbreathing.

Skin contact can cause a rash, itching, or blisters.

Sumithrin is not very toxic to mammals, but it is highly toxicand fish.


213/315

Crop-Dusting NYC? Aerosolized liquids sprayed over large areas of the city.

Terrorism concern?

New vector for urban area.


214/315

Public Health

Considerationsll


215/315

ConsiderationsSurveillance

SurveillanceSince 2000, the NYC DOHMH has conducted comprehensive arthropodisease surveillance and control. In 2003, efforts will again focus on mcontrol through reduction of breeding sites and application of larvicidaddition, comprehensive mosquito, avian and human data collected d

2000-2002 seasons have allowed NYC DOHMH to develop more sensitsurveillance criteria for determining the level of WN viral activity in bi


216/315

surveillance criteria for determining the level of WN viral activity in bimosquitoes that may indicate a significant risk for a human outbreak. indicators will be monitored citywide to identify areas at risk for humatransmission.

Standing Water ReportingThe Department of Health & Mental Hygiene is now acceptiof standing water. However, we will not be able to visit and treported nuisances. Therefore we are encouraging City resid

business owners to take immediate action to eliminate stanon their property.


217/315

p p y

Dead-Bird Reporting Online form

http://www.nyc.gov/html/doh/html/wnv/wnvbird.html

The Department of Health & Mental Hygiene is now accepti

of dead birds. Only a sample of dead birds that meet specifiwill be picked up and tested for the West Nile virus. Howeve
http://www.nyc.gov/html/doh/html/wnv/wnvbird.htmlhttp://www.nyc.gov/html/doh/html/wnv/wnvbird.html


218/315

will be picked up and tested for the West Nile virus. Howevereport of a dead bird is extremely important to us because dreports may indicate the presence of West Nile virus. If you receive a call back from the Department of Health within twbusiness days of making your report, please dispose of the b

Mosquito TestingFive pools of mosquitoes collected in New York City have tested positWest Nile (WN) virus. These include a pool ofCulex salinarius, a humamosquito, collected on July 15, in the Willowbrook Park area of Statenpool of Culex restuans, primarily a bird-biting mosquito, collected fro

Park, Queens on July 17, a pool ofCulex pipiens, a mosquito that bitesand humans, collected from the Hunts Point area of the Bronx on July


219/315

and humans, collected from the Hunts Point area of the Bronx on July ofCulexspecies collected from Jamaica Bay, Queens on July 16, and a Culex salinarius collected from Greenwood Cemetery, Brooklyn on Julpositive pools are the first evidence of West Nile (WN) virus in New Yo2003

Disease ReportingThe New York City Department of Health and Mental HygieDOHMH) is again requesting that during the peak adult mosseason, from June 1 October 31, 2003, all suspected cases

encephalitis (all ages) and viral meningitis (adults only) be rimmediately by telephone or facsimile and that appropriate


220/315

laboratory specimens (cerebrospinal fluid and sera) be submpromptly for testing for West Nile (WN) virus.

POLIOMYELITIS


221/315

POLIOMYELITIS


222/315

What is Poliomyelitis? polio= gray matter

Myelitis= inflammation of the spinal cord

This disease result in the destruction of motor neurons causpoliovirus.

f


223/315

Polio is causes by a virus that attacks the nerve cells of the bspinal cord although not all infections result in sever injuriesparalysis.

When was it reported? Poliomyelitis was recorded in the late 1700s with the first e

the late 1800s.

The cases that were reported in 1979 where mild and self-li

do not result in paralysis.


224/315

How is polio transmitted? Poliovirus is transmitted through both oral and fical routes w

implantation and replication occurring in either the orapgarand or in the intestine of mucosa. Polio cases are most infec

10 days before and after clinical symptoms begin.


225/315

What are the symptoms? Many include fever, pharyngitis, headache, anorexia, nausea

vomiting. Illness may progress to aseptic meningitis andmenigoencephalitis in 1% to 4% of patients. These patients

higher fever, myalia and sever headache with stiffness of theback.


226/315

Polio in children
http://tm.wc.ask.com/r?t=an&s=p&uid=0D84491B2F2231504&sid=124738D5C207A8804&qid=338CF7577F473C4AB3248DDD86845A21&io=12&sv=za5cb0de8&o=0&ask=polio&uip=cdbc74c9&en=is&eo=-100&pt=&ac=7&qs=1&pg=8&u=http://pictures.ask.com/redir?bpg=http%3a%2f%2fpictures.ask.com%2fpictures%3fq%3dpolio%26o%3d0%26page%3d8&q=polio&u=http%3a%2f%2fwww.rds-online.org.uk%2fmilestones%2fpolio.html&s=p&bu=http%3a%2f%2fwww.rds-online.org.uk%2fmilestones%2fpolio.html&qte=0&o=0&isimageSearch=true&fromImagePage=False&iskey=&thumbsrc=http%3a%2f%2fimages.picsearch.com%2fis%3f32355078933&imagesrc=http%3a%2f%2fwww.rds-online.org.uk%2fimages%2fpolio.jpg&thumbwidth=128&thumbheight=108http://tm.wc.ask.com/r?t=an&s=p&uid=0D84491B2F2231504&sid=124738D5C207A8804&qid=338CF7577F473C4AB3248DDD86845A21&io=7&sv=za5cb0dc6&o=0&ask=polio&uip=cdbc74d2&en=is&eo=-100&pt=&ac=7&qs=1&pg=6&u=http://pictures.ask.com/redir?bpg=http%3a%2f%2fpictures.ask.com%2fpictures%3fq%3dpolio%26o%3d0%26page%3d6&q=polio&u=http%3a%2f%2fwww.mumbai.de%2ffpage_01.htm&s=p&bu=http%3a%2f%2fwww.mumbai.de%2ffpage_01.htm&qte=0&o=0&isimageSearch=true&fromImagePage=False&iskey=&thumbsrc=http%3a%2f%2fimages.picsearch.com%2fis%3f489110965089&imagesrc=http%3a%2f%2fwww.mumbai.de%2ffpage_01.jpg&thumbwidth=128&thumbheight=108http://tm.wc.ask.com/r?t=an&s=p&uid=0D84491B2F2231504&sid=124738D5C207A8804&qid=338CF7577F473C4AB3248DDD86845A21&io=7&sv=za5cb0dc6&o=0&ask=polio&uip=cdbc74d2&en=is&eo=-100&pt=&ac=7&qs=1&pg=6&u=http://pictures.ask.com/redir?bpg=http%3a%2f%2fpictures.ask.com%2fpictures%3fq%3dpolio%26o%3d0%26page%3d6&q=polio&u=http%3a%2f%2fwww.mumbai.de%2ffpage_01.htm&s=p&bu=http%3a%2f%2fwww.mumbai.de%2ffpage_01.htm&qte=0&o=0&isimageSearch=true&fromImagePage=False&iskey=&thumbsrc=http%3a%2f%2fimages.picsearch.com%2fis%3f489110965089&imagesrc=http%3a%2f%2fwww.mumbai.de%2ffpage_01.jpg&thumbwidth=128&thumbheight=108http://tm.wc.ask.com/r?t=an&s=p&uid=0D84491B2F2231504&sid=124738D5C207A8804&qid=338CF7577F473C4AB3248DDD86845A21&io=7&sv=za5cb0dc6&o=0&ask=polio&uip=cdbc74d2&en=is&eo=-100&pt=&ac=7&qs=1&pg=6&u=http://pictures.ask.com/redir?bpg=http%3a%2f%2fpictures.ask.com%2fpictures%3fq%3dpolio%26o%3d0%26page%3d6&q=polio&u=http%3a%2f%2fwww.mumbai.de%2ffpage_01.htm&s=p&bu=http%3a%2f%2fwww.mumbai.de%2ffpage_01.htm&qte=0&o=0&isimageSearch=true&fromImagePage=False&iskey=&thumbsrc=http%3a%2f%2fimages.picsearch.com%2fis%3f489110965089&imagesrc=http%3a%2f%2fwww.mumbai.de%2ffpage_01.jpg&thumbwidth=128&thumbheight=108http://tm.wc.ask.com/r?t=an&s=p&uid=0D84491B2F2231504&sid=124738D5C207A8804&qid=338CF7577F473C4AB3248DDD86845A21&io=7&sv=za5cb0dc6&o=0&ask=polio&uip=cdbc74d2&en=is&eo=-100&pt=&ac=7&qs=1&pg=6&u=http://pictures.ask.com/redir?bpg=http%3a%2f%2fpictures.ask.com%2fpictures%3fq%3dpolio%26o%3d0%26page%3d6&q=polio&u=http%3a%2f%2fwww.mumbai.de%2ffpage_01.htm&s=p&bu=http%3a%2f%2fwww.mumbai.de%2ffpage_01.htm&qte=0&o=0&isimageSearch=true&fromImagePage=False&iskey=&thumbsrc=http%3a%2f%2fimages.picsearch.com%2fis%3f489110965089&imagesrc=http%3a%2f%2fwww.mumbai.de%2ffpage_01.jpg&thumbwidth=128&thumbheight=108http://tm.wc.ask.com/r?t=an&s=p&uid=0D84491B2F2231504&sid=124738D5C207A8804&qid=338CF7577F473C4AB3248DDD86845A21&io=7&sv=za5cb0dc6&o=0&ask=polio&uip=cdbc74d2&en=is&eo=-100&pt=&ac=7&qs=1&pg=6&u=http://pictures.ask.com/redir?bpg=http%3a%2f%2fpictures.ask.com%2fpictures%3fq%3dpolio%26o%3d0%26page%3d6&q=polio&u=http%3a%2f%2fwww.mumbai.de%2ffpage_01.htm&s=p&bu=http%3a%2f%2fwww.mumbai.de%2ffpage_01.htm&qte=0&o=0&isimageSearch=true&fromImagePage=False&iskey=&thumbsrc=http%3a%2f%2fimages.picsearch.com%2fis%3f489110965089&imagesrc=http%3a%2f%2fwww.mumbai.de%2ffpage_01.jpg&thumbwidth=128&thumbheight=108http://tm.wc.ask.com/r?t=an&s=p&uid=0D84491B2F2231504&sid=124738D5C207A8804&qid=338CF7577F473C4AB3248DDD86845A21&io=3&sv=za5cb0dc1&o=0&ask=polio&uip=cdbc74c9&en=is&eo=-100&pt=&ac=7&qs=1&pg=2&u=http://pictures.ask.com/redir?bpg=http%3a%2f%2fpictures.ask.com%2fpictures%3fq%3dpolio%26o%3d0%26page%3d2&q=polio&u=http%3a%2f%2fwww.ibabydoc.com%2fonline%2fimages%2fillnesses%2fpolio9.htm&s=p&bu=http%3a%2f%2fwww.ibabydoc.com%2fonline%2fimages%2fillnesses%2fpolio9.htm&qte=0&o=0&isimageSearch=true&fromImagePage=False&iskey=&thumbsrc=http%3a%2f%2fimages.picsearch.com%2fis%3f393472259799&imagesrc=http%3a%2f%2fwww.ibabydoc.com%2fonline%2fimages%2fillnesses%2fimg0009.jpg&thumbwidth=85&thumbheight=128


227/315

Can it cause paralyzes? Paralytic disease occurs 0.1% to 1% of those who become in

with the polio virus.

Paralysis of the respiratory muscles or from cardiac arrest if

neurons in the medulla oblongata are destroyed. Patients have some or full recovery from paralysis usually a
http://tm.wc.ask.com/r?t=an&s=p&uid=0D84491B2F2231504&sid=124738D5C207A8804&qid=338CF7577F473C4AB3248DDD86845A21&io=12&sv=za5cb0de8&o=0&ask=polio&uip=cdbc74c9&en=is&eo=-100&pt=&ac=7&qs=1&pg=8&u=http://pictures.ask.com/redir?bpg=http%3a%2f%2fpictures.ask.com%2fpictures%3fq%3dpolio%26o%3d0%26page%3d8&q=polio&u=http%3a%2f%2fwww.rds-online.org.uk%2fmilestones%2fpolio.html&s=p&bu=http%3a%2f%2fwww.rds-online.org.uk%2fmilestones%2fpolio.html&qte=0&o=0&isimageSearch=true&fromImagePage=False&iskey=&thumbsrc=http%3a%2f%2fimages.picsearch.com%2fis%3f32355078933&imagesrc=http%3a%2f%2fwww.rds-online.org.uk%2fimages%2fpolio.jpg&thumbwidth=128&thumbheight=108http://tm.wc.ask.com/r?t=an&s=p&uid=0D84491B2F2231504&sid=124738D5C207A8804&qid=338CF7577F473C4AB3248DDD86845A21&io=3&sv=za5cb0dc1&o=0&ask=polio&uip=cdbc74c9&en=is&eo=-100&pt=&ac=7&qs=1&pg=2&u=http://pictures.ask.com/redir?bpg=http%3a%2f%2fpictures.ask.com%2fpictures%3fq%3dpolio%26o%3d0%26page%3d2&q=polio&u=http%3a%2f%2fwww.ibabydoc.com%2fonline%2fimages%2fillnesses%2fpolio9.htm&s=p&bu=http%3a%2f%2fwww.ibabydoc.com%2fonline%2fimages%2fillnesses%2fpolio9.htm&qte=0&o=0&isimageSearch=true&fromImagePage=False&iskey=&thumbsrc=http%3a%2f%2fimages.picsearch.com%2fis%3f393472259799&imagesrc=http%3a%2f%2fwww.ibabydoc.com%2fonline%2fimages%2fillnesses%2fimg0009.jpg&thumbwidth=85&thumbheight=128


228/315

Patients have some or full recovery from paralysis usually awith proximally 6 months

Physical therapy is recommended for full recovery.

Treatment Bed rest with close monitoring of respiratory and cardiovasc

functioning is essential during the acute stage of poliomyeliwith fever control and pain relievers for muscle spasms.

Mechanical ventilation, respiratory therapy may be neededdepending of the severity of patients.


229/315

Vaccine Polio vaccine first appeared to be licensed in the United Stat

1955.

Advantages:

Ease to administration

Good local mucosal immunity
http://tm.wc.ask.com/r?t=an&s=p&uid=0D84491B2F2231504&sid=124738D5C207A8804&qid=338CF7577F473C4AB3248DDD86845A21&io=0&sv=za5cb0d89&o=0&ask=polio&uip=cdbc7493&en=is&eo=-100&pt=&ac=7&qs=1&pg=5&u=http://pictures.ask.com/redir?bpg=http%3a%2f%2fpictures.ask.com%2fpictures%3fq%3dpolio%26o%3d0%26page%3d5&q=polio&u=http%3a%2f%2fwww.polioplus.us%2f&s=p&bu=http%3a%2f%2fwww.polioplus.us%2f&qte=0&o=0&isimageSearch=true&fromImagePage=False&iskey=&thumbsrc=http%3a%2f%2fimages.picsearch.com%2fis%3f911523601502&imagesrc=http%3a%2f%2fwww.polioplus.us%2fImages%2fvaccine.jpg&thumbwidth=85&thumbheight=128


230/315

Good local mucosal immunity

Disadvantage:

Strict cold shipping & storage requirements

Multiple doses required to achieve high humeral conservatiagainst all virus types

Vaccine (continuation)

Babies are given 4 doses through out their infancy.

Adolescents and adults should get vaccinated as weAdolescents younger than 18 should receive theroutine four doses.

You should get it if you travel outside places wherepolio id still an epidemic
http://tm.wc.ask.com/r?t=an&s=p&uid=0D84491B2F2231504&sid=124738D5C207A8804&qid=338CF7577F473C4AB3248DDD86845A21&i

Documents

CNS Disorders (CD Nursing)