Lec 28 MMR Flashcards
What are symptoms of measles?
- rash covering childs arm and stomach
- lasts ~4 days
What are characteristics of measles virus?
- paramyxovirus family
- negate strand
- non-segmented
- RNA
- 6 genes encoding 8 proteins
- enveloped
- lipid envelope has viral H and F glycoproteins
- nucleocapsid contains viral RNA, N, P, and L
What are the 3 proteins encoded by measles P gene? and their roles?
P/C/V
P = phosphoprotein required for polymerase activity
V = accessory protein blocks innate immune response
C = accessory protein blocks innate immune response
What is the measles replication cycle?
attachment: by H protein binds CD46, SLAM, Nectin 4
fusion: mediated by F protein
replication and transcription: cat by vRNA dependnent RNA polymerase [L and P], occurs in cytoplasm
budding: mediated by M protein
What mediates measles attachment?
H protein
what mediated measles fusion?
F protein
what mediates measles replication and transcription?
L and P proteins
– viral RNA dependent RNA polymerase
what mediates measles budding?
M protein
What are clinical manifestations of measles?
- childhood infection spread by respiratory route
- latent period 10-14 days –> 2-3 days of prodrome [fever, cough, conjuncitivits, coryza, kopliks spots in mouth] –> characteristic rash
- onset of rash coincides with immune response and initiation of viral clearance
- rash is maculopapular – fat, red area covered with small bumps
How is measles transmitted/spread?
- transmitted via respiratory droplets entering resp tract
- initial infaction in macrophages and dendritic cells of resp tract
- infected cells transport virus to lymphoid tissue –> amplified –> viremia –> tissues
- virus spread in tissues occurs via release of virus or cell-cell fusion leading to formation syncytium [giant multi-nucleated cells]
What are koplik’s spots?
- pinpoint gray-white spots [grain of salt appearance]
- on mucous membranes
What are characteristics of measles rash?
- maculopapular
- beings on face –> trunk and extremities
- fever and severe symptoms lessen as rash progresses
- associated with beginning of cell mediated immunity
What are possible complications of measles?
- bacterial superinfection [common]
- immune suppression caused by infection –> TB reactivation
- severe in immuno-compromised pts
- postinfectious or acute disseminated encephalomyelitis [ADME]
- subacute sclerosing panencephalitis [SSPE]
What are signs of bacterial superinfection in measles?
- otitis media
- mastoiditis
- sinusitis
- pneumonia
What is ADME?
- acute disseminated encephalomyelitis
- possible complication of measles
- autoimmune demyelinating disease 3-14 days after illness onset
What is SSPE? signs and symptoms?
subacute sclerosing panencephalitis
- rare neuro disease in children associated with measles infection
- occurs 6-10 yrs after measles
- most often in children with infection at < 2yrs old
signs: measles virus antibody elevated in serum and CSF, evidence of virus in glial cells and neurons
symptoms: personality change, progressive intellectual deterioration, motor and ANS dysfunction, death
How is measles diagnosed?
- clinical findings
- lab diagnostics:
- — direct detection of virus antigen in epithelial cells by FAS
- — RT-PCR detection of virus RNA
- — serology
- — virus isolation
What are the 3 symptoms that are case definition of clinical measles diagnosis?
- generalized maculopapular rash for 3 or more days
- fever [101 F, 38.3 C]
- either cough, coryza, or conjunctivitis
How is measles transmitted?
- very contagious
- by aerosol transmition
- humans are only host, primary children
What is immune response to measles?
- long lived immunity —> if get it once you won’t get it again
- maternal antibodies protect for up to 6 months old
- immune suppression during infection, cellular response clears infection
What is treatment for measles?
no specific therapy
What is the measles vaccine? who can get it?
- live attenuated virus vaccine
- administered with mumps and rubella as MMR
- give to 12-15 mo old children, revaccination at 4-6 yrs
- not for: pregnant, TB, immunocompromised
What causes mumps?
- mumps virus
What are symptoms of mumps?
- swelling of salivary glands [particularly parotid]
What are viral properties of mumps virus?
- paramyxovirus family [genus rubulavirus]
- negative strand
- non-segment
- RNA virus
- enveloped
What are the virulence factors of mumps virus?
in envelope - Hemagluttinin/neuraminidase [HN] - Fusion [F] matrix [M] in capsid - nucleoprotein [N] - phosphoprotein [P] polymerase [L]
What is pathogenesis of mumps infection?
- virus enters respiratory tract
- virus grows in salivary glands and local lymphoid tissue
- virus spreads to spleen and distant lymphoid tissue [at 7-10 days]
- viremia [at 15 days]
- virus spreads through body to glandular tissue and CNS [18 days and after]
What are the clinical symptoms associated with mumps replicating in salivary glands?
fever, inflammation of lymph nodes, parotitis
What are the clinical symptoms associated with mumps replicating in meninges?
meningitis [10%]
What are the clinical symptoms associated with mumps replicating in brain?
encephalitis [rare]
What are the clinical symptoms associated with mumps replicating in kidney?
no clinical consequences
What are the clinical symptoms associated with mumps replicating in testis/ovary?
orchitis [in 20% of adult males
What are the clinical symptoms associated with mumps replicating in mammary gland?
mastitis [in 10% of post-puberal femals
What are the clinical symptoms associated with mumps replicating in pancreas/thyroid/myocardium/joints?
pancreatitis, thyroiditis, myocarditis, arthritis
What are most common clinical signs of mumps?
- meningitis [in 10%]
- orchitis [testis inflamed] in 20% of adult males
- mastitis [mammary gland inflamed] in 10% of post pubertal females
What is mumps vaccine?
- live attenuated virus vaccine
- single serotype
- administered as MMR
What is epidemiology of mumps [who gets it]?
- mostly children age 5-8
- outbreaks in adults in high density [military]
How is rubella transmitted?
respiratory secretions
who gets rubella?
both children and adults get mild disease with maculopapular rash
What are characteristics of rubella virus?
- togavirus
- positive single strand
- RNA
- enveloped
- isocahedral nucleocapsid
What is congenital rubella syndrome
- get it in early months of pregnancy
- associated with high rate of birth defects
- mother gets viremia, goes through placenta to fetus, fetus gets chronic infection
- 20% chance of damage to fetus if woman infected in first trimester
What are symptoms of congenital rubella syndrome?
deafness [most common]
also: cataracts, heart defect, mental retardation, microcephaly, liver/spleen damage
What is rubella vaccine?
- live attenuated
- single serotype
- given as MMR