viral spread-- polio, measles and small pox Flashcards
what's going on? 22 yo woman with: gen fever and malaise headache, neck and back pain acute leg weakness which became lower extremity weakness and resp. failure CSF: lymph. pleocytosis and prot MRI: ant horn cell involvement no WNV or DENV Abs present recent travel to central/south america never had polio vaccine
Pt had not been vaccinated with polio and was exosed to a child in Costa Rica who had been vaccinated with live polio vaccine virus. She developed a vaccine-associated paralytic poliomyelitis
what are the risks for someone who has never been vaccinated agst polio if they are exposed to the live vaccine
they can develop vaccine-associated poliomyelitis
poliomyelitis– what is it?
what happens in extreme cases?
inflammation of the gray matter of the spinal cord and brain due to infection with poliovirus.
extreme cases: flacid paralysis of limb muscles and resp muscles
what are located in the anterior horn of the spinal cord that are affected by polio?
anterior horn cells, which are the cell bodies of motor neurons —> leading to paralysis
As of 2012, polio is endemic in which 3 countries?
- nigeria
- afghanistan
- pakistan
(it was just eradicated in India)
though polio has been eradicated in most countries, what is it called when the wild-type is reintroduced due to travel to endemic areas?
re-establishment
the 4 levels of severity of polio
- inapparent or subclinical polio (90-95%) of cases
- abortive polio (4-8%)- normal symptoms of a viral ifxn– fever, sore throat and headache
- Aseptic meningitis (no presence of bact in CSF) or non-paralytic polio (1%)– headache, fever, stiff neck, PMNs and then lymph in CSF
- Paralytic polio (.1%)- sore throat, headache, vomiting for 1-2 days. 5-10 days: meningitis followed by flacid paralysis. The Bulbar form of paralytic polio also leads to respiratory paralysis because of infection of the brainstem (medulla oblongata)
symp assoc w/ inapparent or subclinical polio?
none– but they express polio Abs– 90% of people!
symp assoc with abortive polio
typical of any viral ifxn: sore throat, fever, headache. 4-8% of polio cases
symp. assoc with aseptic meningitis/non-paralytic polio
(1%)– headache, fever, stiff neck, PMNs and then lymph in CSF
symp assoc. w/paralytic polio? Bulbar form of polio?
sore throat, headache, vomiting for 1-2 days. 5-10 days: meningitis followed by flacid paralysis. The Bulbar form of paralytic polio also leads to respiratory paralysis because of infection of the brainstem (medulla oblongata)
symp associated with the Bulbar form of polio?
The Bulbar form of paralytic polio leads to respiratory paralysis because of infection of the brainstem (medulla oblongata) in addition to flacid paralysis caused by infection of the anterior horn cells in the gray matter
how is a country deemed as polio free?
no polio cases for three years
A country re-established with Polio is a country that (+3 examples)
active and persistent poliovirus transmission for more than 12 months following an importation (ie angola, chad, dem. repub of congo)
countries with imported polio are countries experiencing
ongoing outbreaks following an importation (there is an “importation belt” in north/central africa. Maruitania is the most northern country)
what is post polio syndrome?
symptoms of fatigue, muscle weakness/muscle atrophy and pain 30-40 yrs after recovery from polio (some poeple were asymptomatic originally and didn’t even know that they had polio) due to a persistent polio ifxn in the nerve or muscle
- people are now coming into the clinic with this!
what is the txt for post-polio syndrome?
maybe antivirals?
the polio virus- what family: enveloped or no: capsid shape: genome:
the polio virus- what family: picornaviridae enveloped or no: unenveloped capsid shape: icosahedral protein capsid genome: 1 mol of + ssRNA
how many serotypes of polio?
3– all on epitopes of surface proteins VP1, VP2 and VP3
which of the 3 polio serotypes are common, and what impact did this have on vaccine?
all 3 are common, so all 3 are used in the vaccine
how does polio get into the body?
it’s ingested, so it has to be able to survive the bile salts/acidity of the stomach
poliovirus replication (7 steps)
- binds to host cell
- endocytosis
- makes a pore in endosomal membrane and + RNA is released into the cytoplasm
- the + stranded RNA is translated directly into the proteins —> cleaved into 3 prots by protease that is part of hte viral protein (P1, P2 and P3)
- P1 is cleaved into 3 prots which assemble into a viral capsid
- P2 and P3 replicate the + strand into a negative strand, from which they copy this into the positive strand.
- the +RNA copies are then either 1) used for further translation of more proteins or 2) packaged into the progeny virus capsid that was created with P1
what does polio virus do to cells?
it has a cytopathic effect– the cells round up, lyse and float off of culture
spread of polio within a person
- ingested in GI tract
- replicate in GI epithelium
- enter GALT (ie peyer’s patches)
- drain to lymphnodes
- enter blood stream (viremia)
- infect other internal organs, specifically anterior horn cells in the spinal cord (paralysis) and the medulla oblongata (resp failure)
in order to infect the anterior horn cells and the medulla oblongata, polio has to pass what? how does it do it?
it has to pass the blood brain barrier (BBB) to get to the medulla oblongata and the blood-CSF barrier to get to the anterior horn cells. It likely does this by infecting the epithelium, but it’s uncertain.
what is the timeline with polio for when you would feel initial symptoms of being infected in the gut (ie fever, headache, sore throat)?
meningitis/paralysis?
Ab presence?
viremia?
infected in the gut (ie fever, headache, sore throat): peaks around 4 days post exposure
meningitis/paralysis: seen about 10 days post exposure (bc it needs time to replicate)
Ab presence: dvp about day 7 and persist for life
viremia: mainly seen days 3-7. Is transient and allows the spread fro mthe gut —> brain/spinal cord
besides spreading from the lymphoid tissue to the blood, what is another possible route for polio to get from the gut to the brain stem?
the vagal nerve which goes from the GI tract to the brain stem
when polio infects anterior horn cells what happens histologically?
nisal, cytoplasm becomes basophilic, nucleus shrinks, large eosinophilic inclusion bodies are present bodies get smaller and then disappear entirely (chromatolysis)
tranmission of polio is primarily:
fecal-oral (food and water contamination)
what is normal season for transmission of polio, and why?
warm weather– usually spread via lakes/pools during summer camp that are infected with virus via stool
3 phases of polio ifxn in history
- endemic phase: ancient times-late 1800s. Ifxns were early in life, when babies were protected by maternal Abs, so they didn’t get as sick, they were able to fend off polio
- epidemic phase: late 1800s-early 1900s- increased hygiene led to ifxn later in life (when kids were on longer protected by maternal Abs) and more severe disease
- vaccine era- 1950s-present. Disease in unimmunized or those with inadequate protection
2 types of polio vaccine
- Inactivated polio vaccine (IPV)– virus is grown in monkeys andformalin-inactivated , is no longer infectious but it produces Ab response
- Oral Polio Vaccine (OPV)– grown in cell culture and mutated until it’s not infectious in monkeys
where are the primary attentuating mutations in the OPV that make it non-infectious?
at the internal ribosome entry site, which alters the natural stem-loop structure and reduces the ability of hte viral RNA to be translated, esp in neurons. It does still replicate well in the GI tract.
Advantages of IPV (3)
- no live virus that can regain virulence/cause disease
- strong humoral immunity
- can be incorporated with other vaccines (DPT)
Disadvantages of IPV (4)
- requires injection (parenteral administration)
- Fails to induce mucosal immunity
- Quality control needed tor potency and inactivation
- Expensive
Advantages of OPV (4)
- confers both mucosal and humoral immunity
- immunity may be lifelong
- easy to administer (don’t need trained prof)
- inexpensive
Disadvantages of OPV (2)
- can mutate to virulent form
2. cold chain needed for transport
current vaccination recs abt polio in western world? future recs?
4 doses of IPV (2, 4, 6-18 mos and 4-6 yrs). IPV confers less immunity, but there were 10 cases/yr of vaccine related polio from OPV, so it’s the vaccine of choice)
future: once eradicated, potentially no vaccine? As of now serotype 2 has stopped, so might go to a monovalent type 1 and type 3 vaccines which are more effective
what are 2 things that have slowed the eradication of polio?
- war
2. govt and religious leaders opposed to vaccination in certain areas
why is the live virus OPV dangerous?
bc live virus OPV replicates in the Gi tract and reversion of point mutations can occur, giving rise to shed revertant viruses. Then other people can be exposed —> infected
how is measles transmitted?
inhalation of earosols via respiratory route
incubation period for measles
10-14 days
3 “Cs” of measles
cough, coryza (cold like symptoms– runny nose, etc) and conjunctivitis
prodromal period of measles
2-3 day period of fever, cough, coryza and conjunctivitis
classic presentation of measles?
red maculopapular rash, in addition to 2-3 days of fever, cough, coryza and conjunctivitis
measles- family: enveloped? capsid shape? genome: Surface glycoprots:
measles-
family: paramyxoviridae
enveloped: yes, lipid envelope
capsid shape: pleiotropic particle with helicle nucleocapsid
genome: negative stranded ssRNA
Surface glycoprots: H (hemagglutinin) and F (fusion)
difference between hemagglutinin function in influenza and measles
in influenza, it serves to bind the virus to the host cell and to fuse the membrane of the virus with the membrane of the host cell. In measles, the hemagglutinin only serves to bind the virus. It has a separate fusion protein
Measles virus RNA metabolism
- ssRNA —> virion RNA polymerase copies it into multiple subgenomic + mRNA which is used to encode proteins that then replicate the -ssRNA into +RNA and back into the -strand RNA to be inserted into the progeny virus
4 important proteins made by the subgenomic RNA in measles
- N- nucleocapsid prot
- M- matrix prot
- F- fusion
- HN- hemagglutinin
how does measles exit the cell?
viral proteins embed in the host cell membrane and then the new viruses use these proteins to bud off of the host cell
how does polio exit the cell?
they lyse the cell and then exit– CHECK THIS- IT MIGHT BE WRONG
koplik’s spots
white spots in mouth/oral mucosa bc of lymph infiltration. It appears a little bit before the rash
what happens to the immune system when there’s a rash during a measles ifxn?
during the period of the rash, t-cells are immunosuppressed, so people become suceptible to other ifxns
why do we vaccinate for measles?
bc though most cases only result in a rash, some lead to Postinfectious encephalomyelitis (PIE), Inclusion encephalitis and Subacate sclerosing panencephalitis (SSPE)
Postinfectious encephalomyelitis (PIE)-the serious but rare ourcome of measles host immune response at the time: age of ifxn: incidence: pathology: time course:
Postinfectious encephalomyelitis (PIE)-the serious but rare ourcome of measles host immune response at the time: normal age of ifxn: > 2 incidence: 10^-3 pathology: inflammation, demyelination time course:monophasic, weeks
Inclusion encephalitis: the serious but rare ourcome of measles host immune response at the time: age of ifxn: incidence: pathology: time course:
Inclusion encephalitis: the serious but rare ourcome of measles
host immune response at the time: immunosuppressed
age of ifxn: any
incidence: ?
pathology: inclusion bodies
time course: progressive, months
subacute sclerosing panencephalitis (SSPE): the serious but rare ourcome of measles host immune response at the time: age of ifxn: incidence: pathology: time course:
subacute sclerosing panencephalitis (SSPE): the serious but rare ourcome of measles host immune response at the time: normal age of ifxn: < 2 incidence: 10^-6 pathology: inclusion bodies time course: progressive, years
for a well nourished child how do measles infect the lung: ear: oral mucosa: conjunctiva: skin: intestinal tract: urinary tract: overall impact:
for a well nourished child how do measles infect the lung: temp. resp illness ear: otitis media oral mucosa: koplik's spots conjunctiva: conjunctivitis skin: maculopapular rash intestinal tract: no leasions urinary tract: virus detectable in urine overall impact: serious disease in very small proportion of those infected
for a malnourished child how do measles infect the lung: ear: oral mucosa: conjunctiva: skin: intestinal tract: urinary tract: overall impact:
for a malnourished child how do measles infect the
lung: life-threatening pneumonia
ear: otitis media is more severe
oral mucosa: severe ulcerating lesions
conjunctiva: severe corneal lesions, secondary bact. ifxn, blindness
skin: hemorrhagic rashes (black measles)
intestinal tract: diarrhea, exacerbates malnutrition, halts growth, impairs recovery
urinary tract: no known complications
Overall impact: major cause of death – 200,000 deaths/yr
the fact that measles is monotypic meant that the ifxn generally leads to
life-long immunity —> it can be eradicated with enough vaccination!
what type of immunity is important for recovery from measles?
cell-mediated (T-cells)
what is the only reservoir for measles?
humans
what was teh down side of the Measles Virus vaccine
provides early protection, but later there’s declining immunity which led to atypical measles: increased fever, severe lesions, pneumonitis due to unbalanced AB response or poor T cell response
current measles vaccination recommendations?
live vaccine after 12 mo of age, usually as part of MMR (or MMRV), and second immunization 4 wks later
clinical characteristics of smallpos
fever, malaise, headache, backache 7-17 days after exposure
rash shortly thereafter: first on face, oropharyngeal mucosa, forearms, spreads to legs and trunk, may involve palsm and soles
the progression of the rash in smallpox
first on face, oropharyngeal mucosa, forearms, spreads to legs and trunk, may involve palsm and soles
maculopapular –> vesicular —> pustular
lesions are all at the same stage of dvpmt
small pox virus
genome:
capsid structure:
lg virion with ds DNA genome in complex capsid structure inside membrane
where is the smallpox DNA genome replicated? and what does it make
in the cytoplasm. it is transcribed by the DNA dependent RNA polymerase, which makes the early proteins, which then uncoat the DNA, so that the DNA cn be replicated to make the late proteins.
how does small pox leave the host cell?
the virus produces a new membrane arch then inserts the virion. Actin helps propel the virus like shigella, and then it spreads through the body
variola major virus causes
severe small pos
variola minor virus causes
less severe smallpox
what is the reservoir for smallpox?
only humans
vaccination recommendations for small pox
none! cesed in 1972 bc no cases in the world since 1977. All lab stocks of the virus have been destroyed by agreement except at CDC and Institute of VIrus prep, moscow
how do we get smallpox?
inhalation of aerosol droplets– then spreads like the measles
how does small pox spread?
virus spreads from initial infected cells to macrophage —> lymphatics (replication) —> blood stream —> dermal vessels —> epidermis where basal cell layer is infected
small pox vesicle formation
edema and necrosis lead to vescicle, PMNs migrate into lumen of vescicle, making it pustular —> pustules progress to dried up crusts
what are the secondary sites of disease for
polio:
measles:
small pox:
what are the secondary sites of disease for
polio: ant. horn cells
measles: internal organs and epidermis
small pox: internal organs and epidermis
Jennerian vaccine approach
using an avirulent related virus from another species (ie small pox)
polio vaccines illustrate which type of viral vaccine approach? how about small pox?
polio: classic viral vaccine– killed viral vaccine vs live, attenuated viral vaccine
small pox: jennerian approach– using a avirulent related virus from another species
