viruses: polio, rabies, HSV Flashcards
POLIOVIRUS - POLIOMYELITIS
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 flaccid, ascending, asymmetrical paralysis.
Old name is infantile paralysis.
poliovirus etiology
An enterovirus -
Human Enterovirus C - Polio viruses
a non-enveloped, +sense RNA virus
poliovirus serotypes
3 serotypes designated as PV1, PV2, and PV3:
infection with one serotype results in lifelong immunity but they do not cross neutralize
An adequate vaccine must contain all three types (i.e., is trivalent).
serotype 1 causes nearly all cases (85%) of paralytic polio.
types 2 and 3 are more often isolated in vaccine-associated poliomyelitis.
poliovirus incidence/prevalence
Rare today in US due to vaccination
Polio was thought to be primarily a disease of developed/industrialized countries. Most cases occurred in slightly older, susceptible children and yong adults who manifested with more serious disease
paralytic polio is a significant concern in underdeveloped countries.
poliovirus transmission
Infection is acquired from an infected or diseased person:
primarily by the fecal-oral route via contaminated food and water.
The virus is present in stool 3-6 weeks.
less so by respiratory secretions/aerosol droplets and saliva (oral-oral transmission).
Highly communicable: Poliovirus is highly infectious, with seroconversion (attack rates?) rates in susceptible household contacts of children nearly 100% and of adults over 90%.
polio reservoir
Humans are the sole host (the virus only infects humans).
Transmission occurs most frequently by persons with inapparent infections. Communicable 7→10 days both before symptoms onset and after onset.
Humans and water are the reservoirs.
Populations affected by PV:
children
PV Seasonality/Temporal pattern
- Summer-fall/autumn (in temperate zone, i.e., Northern hemisphere), little seasonality occurs in the tropics
PV pathogenesis
incubation period??
After virus enters the ??, the virus infects cells and then spreads to draining lymph nodes along the ??, first in pharynx and later in the intestinal tract where infection can persist for weeks to months and the patient may manifest with signs and symptoms.
Incubation period is prolonged (5 → 35 days [average 7 → 14 days]).
This is a lytic virus.
mouth or nose
gastrointestinal tract
The poliovirus is shed in ?? for several weeks and in the ?? for several months.
A ?? will also occur.
oral secretions
feces
viremia
Rarely, the viremia is high.
With the viremia, virus can infect and replicate in brown fat cells, enotheial cells and muscle cells for up to 4 months.
Rarely, the poliovirus enters the CNS by:
crossing the blood-brain barrier.
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.
“Once in the CNS, poliovirus spreads along certain nerve fiber pathways, preferentially replicating in and destroying ?? within the ??.
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” –>Results in ??
motor neurons
spinal cord, brain stem, or motor cortex
paralytic poliomyelitis
lower motor neuronal damage (FLACCID PARALYSIS) with no sensory loss (Unlike GBS).
PV Clinical syndromes following infection
Inapparent/Asymptomatic infection is the most common (90→95%) result.
Disease accounts for remainder of infected persons
Inapparent/Asymptomatic PV infection
Person is either asymptomatic or no more than minor malaise lasting 1→2 days.
virus shed in feces can be detected, are able to transmit the virus to others.
seroconversion occurs.
PV Disease:
Most (4→8%) common disease form – Minor illness/gastroenteritis/abortive poliomyelitis:
fever, malaise, fatigue, drowsiness, headache, muscle aches sore throat/pharyngitis, nausea and vomiting, abdominal pain, constipation, rarely diarrhea.
*Lasts 72 hours or less,
no paralysis
PV disease:
Aseptic meningitis without paralysis/non-paralytic (Abortive illness/Abortive polio (next most common): s/s of minor form and…
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, symptoms resolve, no permanent paralysis
PV disease:
Least (0.1 →2%) common form is paralytic poliomyelitis:
Initially s/s of aseptic meningitis without paralysis but now an acute onset, febrile, ascending, acute asymmetric flaccid paralysis occurs:
paralysis begins 1→ 10days after the early symptoms began.
progresses for two to three days
is usually complete by the time the fever breaks.
Severe muscle aches or spasms, muscle pain
Loss of superficial and deep reflexes (Diminished deep-tendon reflexes/areflexic leg weakness).
for some patients, paralysis is temporary, lasting weeks.
*Sensory involvement - Abnormal sensations (but not loss of sensation-Guillain-Barre) in an area; sensitivity to touch, paresthesia.
paralytic poliomyelitis electromyography/nerve conduction velocity studies demonstrate ??
axonal-type polyneuropathy affecting anterior horn cells or their axons vs. demyelination
3 forms of paralytic poliomyelitis – 3 Different types of paralysis may occur, depending on the nerves involved:
Spinal Bulbar polio Bulbospinal polio
Residual complications of paralytic polio often occur following ??
the initial recovery process.
Post-polio Syndrome:
Some (25% of) paralytic polio survivors from 1940s→1950s are experiencing:
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
ddx of acute flaccid paralysis
ECHO, Coxsackie and Enterovirus 68→71, arbovirus polio/post polio vaccination. tick paralysis. Guillain-Barré’-Syndrome. botulism dumb rabies. myasthenia gravis. intoxication due to poisons.
PV dx
The diagnosis is made by identifying poliovirus in clinical specimens (usually stool) obtained from an acutely ill patient.
Cx on appropriate cell lines followed by identification by neutralization tests or by PCR. (way it’s usually done)
Poliovirus may also be identified by direct amplification from stool specimens followed by partial genomic sequencing to establish identity and possible source of the virus.
Shedding in fecal specimens can be intermittent, but usually poliovirus can be detected for up to 4 weeks after onset of illness.
During the first 3–10 days of the illness, poliovirus can also be detected from oropharyngeal specimens.
Poliovirus is rarely detected in the blood or cerebrospinal fluid.
PV tx
supportive
PV ppx
Inactivated (killed) polio vaccine (IPV) AKA Salk vaccine, AKA IPO
–>Enhanced potency vaccine (e-IPV)
Oral polio vaccine (OPV)
IPV
trivalent.
prepared by formalin inactivation of wt virus grown in primate tissue culture.
Primary series is at least 4 inoculations over a 1→ 2 years
Highly (> 90%) efficacy (seroconversion/immunity).
e-IPV
is more potent than original IPV
results in increased seroconversion rates
is the only IPV vaccine approved in US, i.e., IPV = e-IPV
4 doses e-IPV (IPOL) ONLY to eliminate any chance of vaccine-associated paralytic polio (no OPV or IPV used)
IPV Advantages:
Safe/no risk for unvaccinated persons, e.g., the immunocompromised
IPV limitations
Given parentally (i.e., injected) – more expensive than Oral polio vaccine (OPV) administration.
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 to reach the CNS and serum anti-polio-IgG helps clear virus from these sites.
Boosters are needed. In developing countries, a 4th booster may be required
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
RABIES
acute, fulminant, fatal, focal encephalitis and myelitis due to infection of brain and spinal column
This virus can infect nearly all mammals and is transmitted between them by infected secretions, usually saliva and is fatal to virtually all humans and nearly all mammals.
Human survivors are very rare.
Characteristics of rabies virus, a neurotrophic virus:
Rhabdoviridae group, a Lyssavirus: a (-) ssRNA, bullet–shaped virus (enveloped with helical symmetry)
RV: serotypes
Single serotype (one major surface antigen).
Each virus possess many copies of a single glycoprotein peplomer which is specific for the brain, alter one amino acid in the glycoprotein results in an attenuated strain.
Virus replicates in the ??, forming eosinophilic cytoplasmic inclusions consisting of viral nucleoprotein (??).
cytoplasm
Negri bodies
Rabies: common or rare today?
very rare today because we control infections in cats and dogs.
RV transmission
Animal bites or scratches, contact with animal saliva or excretions.
Other:
Inhalation of aerosols, e.g., bat droppings.
Transplants (Corneal, others) is rare.
Rabies reservoir
The host range is very wide - All mammals are susceptible.
The natural reservoirs are:
domestic with dogs (WW) and cats
feral/sylvatic animals with: skunks, foxes, raccoons, *bats* (US) wolves, others
Geographic distribution of rabies is ??:
In the US, rabies is ??
worldwide
epizootic in feral/sylvatic animals
Rabies Age and Gender and Season:
NA
Rabies Risk factors
Control of human rabies is contingent on control of dog and cat rabies:
Worldwide, infected dogs are the most important source of infection for humans (80→90% of all cases):
In areas of the world where rabies in poorly controlled, dog bites resulting in death due to rabies is common (@50,000 deaths/year world wide).
In the US: vaccination and control programs have eliminated the domestic dog and cat as a reservoir for rabies, thus human rabies in the US is rare ((
From 1980 → 1997 there have been ?? cases of rabies in the US and most (~ ½) of the cases involved ?? which are most common cause of rabies in US.
few (
