CNS Infections- Polio Virus

Question 1

Poliomyelitis (myelitis = inflammation of spinal chord) is an acute systemic infectious disease.
In its rare, severe form, it affects CNS, destroying motor neurons in spinal cord, which results in a _____________.

Answer 1

flaccid, ascending, asymmetrical paralysis. Old name is infantile paralysis

Question 2

Another name for Polio virus is

Answer 2

Human Enterovirus C

Question 3

Polio is an enterovirus - Human Enterovirus C- description

Answer 3

-Polio viruses
-a non-enveloped
+sense RNA virus
-3 serotypes designated as PV1, PV2, and PV3

Question 4

infection with one serotype results in lifelong immunity but they __________
An adequate vaccine must contain __________.

Answer 4

do not cross neutralize

all three types (i.e., is trivalent)

Question 5

Polio is rare today in US due to vaccination. Polio was thought to be primarily a disease of _________. Most cases occurred in slightly __________ who manifested with more serious disease.

Answer 5

developed/industrialized countries

older, susceptible children and young adults

Question 6

Paralytic polio is a significant concern in ____________

Answer 6

underdeveloped countries

Question 7

Infection is acquired from an infected or diseased person, primarily by the ____________.

Answer 7

fecal-oral route via contaminated food and water; virus is present in stool 3-6 weeks.

-less so by respiratory secretions/aerosol droplets and saliva (oral-oral transmission)

Question 8

Host of Polio

Answer 8

Humans are the sole host (the virus only infects humans). Transmission occurs most frequently by persons with inapparent infections.

Question 9

Reservoirs of Polio

Answer 9

humans AND water

Question 10

How communicable is Polio?

Answer 10

Highly communicable: Poliovirus is highly infectious, with seroconversion rates in susceptible household contacts of children nearly 100% and of adults over 90%

Question 11

Populations affected by Polio (list)

Answer 11

1. children less than 3 are primarily affected (in utero, neonatal, infant infections DO NOT normally occur)
2. adolescents and young adults, esp. pregnant women are also susceptible.
3. the elderly
4. Younger pt have less severe manifestations. The likelihood of developing paralytic polio increases with age, as does the extent of paralysis (one limb vs quadriplegia)

Question 12

Seasonality/temporal pattern

Answer 12

Summer-fall (in temperate zone, i.e., Northern hemisphere), little seasonality occurs in the tropics

Question 13

Common pathogenesis/presentation

Answer 13

S/S: no symptoms (majority) or mild malaise

Question 14

Polio is a _____ virus. After virus enters the mouth or nose, the virus infects cells and then spreads to _____________, first in pharynx and later in the intestinal tract where infection can persist for _________ and the patient may manifest with signs and symptoms. The virus is shed in _______ for several weeks and in the feces for several months. A viremia will also occur. Rarely, the viremia is ______.

Answer 14

lytic

draining lymph nodes along the GI tract

weeks to months

oral secretions

high

Question 15

Rarely, the virus enters the CNS by:

Answer 15

1. crossing the blood-brain barrier
2. travels by neural routes (infects skeletal muscle, then travels up innervated nerves of skeletal muscles) and along the PNS via retrograde axoplasmic flow as per herpes, and/or rabies viruses to CNS

Question 16

Once in the CNS, poliovirus spreads along certain nerve fiber pathways, preferentially replicating in and destroying motor neurons within ___________. This leads to the development of _________, the various forms of which (spinal, bulbar, and bulbospinal) vary only with the amount of neuronal damage and inflammation that occurs, and the region of the CNS that is affected.

Answer 16

the spinal cord, brain stem, or motor cortex

paralytic poliomyelitis

Question 17

Spread through CNS results in

Answer 17

lower motor neuronal damage (FLACCID PARALYSIS) with NO sensory loss (unlike GBS)

Question 18

Inapparent/Asymptomatic infection is the most common (90→95%); however disease form manifests in 4-8% of people with these S/S:

Answer 18

• Minor illness/gastroenteritis/abortive poliomyelitis is most common
• fever, malaise, fatigue, drowsiness,
• headache, muscle aches
• sore throat/pharyngitis
• nausea and vomiting, abdominal pain, constipation, rarely diarrhea
• Lasts 72 hours or less

Question 19

Polio also manifest as Aseptic meningitis without paralysis/non-paralytic

(Abortive illness/Abortive polio (3rd most common form) — Signs and Symptoms of aseptic meningitis described earlier plus:

Answer 19

-Pain in front part of neck
-Back pain or backache
-Muscle stiffness, Leg pain (calf muscles)
-Muscle tenderness and spasm in any area of the body
-Pain or stiffness of the back, arms, legs, abdomen
Symptoms usually last 1 - 2 weeks

Question 20

Least (0.1 →2%) common form of diease is paralytic poliomyelitis, S/S:

Answer 20

Initially Signs and Symptoms of aseptic meningitis without paralysis, but is FOLLOWED BY an asymmetric flaccid paralysis that is
ascending, acute onset, with a fever.

Question 21

During the rare paralytic poliomyelitis, paralysis begins 1→ 10 daysafter the early symptoms began. It progresses for two to three days and is usually complete by the time the fever breaks. S/S are:

Answer 21

• Severe muscle aches or spasms, muscle pain
• Loss of superficial and deep reflexes (Diminished deep-tendon reflexes/areflexic leg weakness).
• EMG velocity studies demonstrate axonal-type polyneuropathy affecting anterior horn cells or their axons vs. demyelination

Question 22

Sensory involvement of paralytic poliomyelitis is

Answer 22

abnormal sensations (but not loss of sensation) in an area; sensitivity to touch, paresthesia.

Question 23

3 forms of paralytic poliomyelitis – 3 Different types of paralysis may occur, depending on the nerves involved:

Answer 23

1. Spinal
2. Bulbar polio
3. Bulbospinal polio
   - for some patients, paralysis is temporary, lasting weeks

Question 24

Post-polio Syndrome manifests as:

Answer 24

• unaccustomed fatigue
• new or recurrent muscle weakness and pain
• progressive muscle atrophy
• Peak incidence is 30 → 40 years following acute polio
• Disease develops when patient’s remaining motor units/motor neurons start to respond poorly due to their overuse throughout many years. NOT due to activation of latent poliovirus

Question 25

Differential diagnosis of acute flaccid paralysis:

Answer 25

1. ECHO, Coxsackie and Enterovirus 68→71,
   2. arbovirus
   3. polio/post polio vaccination.
   4. tick paralysis.
   5. Guillain-Barré’-Syndrome.
   6. botulism.
   7. dumb rabies.
   8. myasthenia gravis.
   9. intoxication due to poisons.

Question 26

Diagnosis is usually made by identifying poliovirus in stool sample, but it may also be identified by

Answer 26

direct amplification from stool specimens followed by partial genomic sequencing to establish identity and possible source of the virus. (rarely detected in blood of CSF)

Question 27

Treatment and Prophylaxis

Answer 27

Tx: supportive 
Prophylaxis:
1. Inactivated (killed) polio vaccine (IPV)
2. Enhanced potency vaccine (e-IPV)
3. Oral polio vaccine (OPV) aka Sabin

Question 28

Inactivated (killed) polio vaccine (IPV) description

Answer 28

-AKA Salk vaccine
-is trivalent
-is prepared by formalin inactivation of wt virus grown in primate tissue culture.
-Primary series is at least 4 inoculations over a 1→ 2 years
-High efficacy due to seroconversion/immunity
(> 90%)

Question 29

Enhanced potency vaccine (e-IPV) description

Answer 29

• is more potent than original IPV

- is the only IPV vaccine approved in US, i.e., IPV = e-IPV

Question 30

Advantages of e-IPV (newer, more used version of IPV)

Answer 30

-Safe/no risk for unvaccinated persons, e.g., the immunocompromised.

Question 31

Limitations of e-IPV (newer, more used version of IPV)

Answer 31

1. Given parentally (i.e., injected) – more expensive than Oral polio vaccine (OPV) administration.
2. Does not generate high sIgA responses but rather a serum IgG response. This response is still efficacious since if a vaccinated person is exposed to WT virus, the WT virus must first disseminate in blood and lymphatics before reaching the CNS, and serum anti-polio-IgG helps clear virus from these sites.
3. Boosters are needed. In developing countries, a 4th booster may be required.
4. Only protects those actually vaccinated. So religious/philosophical groups not participating in vaccine program can/do occasionally become infected in local outbreaks → the spread of wild-type (wt) virus.

Question 32

Oral polio vaccine (OPV) aka Sabin description

Answer 32

• trivalent vaccine
• live attenuated virus which replicates in oropharynx and intestinal tract but cannot infect neuronal cells, less transimisable than wt virus.
• OPV has significant advantages over e-IPV

Question 33

Limitations to Oral polio vaccine (OPV) Sabin

Answer 33

1. Puts other unvaccinated family members and contacts at risk, may spread to immunocompromised persons. (bc live virus)
2. During viral replication in vaccinated children, the attenuated virus mutates back to the virulent/wt virus , but only causes extremely rare cases of vaccine-associated paralytic polio/poliomyelitis (VAPP) in the US (8→10 cases/year).
3. Vaccine-derived poliovirus can actually circulate in the population, (cVDPV)

Question 34

Current vaccine recommendations

Answer 34

4 doses e-IPV (IPOL) ONLY