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TM: Rabies (i) (Pathogenesis (incubation period = inoculation - CNS…
TM: Rabies (i)
Pathogenesis
inoculation via bite/lick
may replicate in muscle cells prior to neurons
enters PNS before CNS via binding to ACh Rs @ NMJ
incubation period = inoculation - CNS symptom onset
more distal peripheral bite, e.g. limbs = longer incubation
4 days - 19 yrs
< 60 days in 70% of cases
most dangerous: bites on face, neck, hands, multiple bites
catastrophic infection can be averted before entry to CNS
in PNS virus retrograde transport to CNS @ 5-10cm/day!
massive rep in CNS
intracellular accumulation of protein
NEGRI BODIES = dx
remains intraneuronally in CNS - immune evasion, hence fatal
alters NT secretion
centrifugal (from centre) spread from Ns to tissues
salivary gland (foaming @ mouth, want to bite)
lacrimal gland
extracellular rep responsible for transmissibility
some suppression of natural host immune mechanisms by virus - low IFN production
Intro
highly endemic in central + tropical S America, India (most affected) + Far East
invariably fatal once contracted
bat rabies also occurs (theoretical risk in Ire + Scotland)
Genus Lyssavirus, part of rhabdoviridae family
enveloped, ssRNA, distinct bullet shape
most deaths in Asia (india) + Africa
endemic in most of world
usually affects males aged 1-14
dogs account for > 99% of cases
other animals: canids (foxes, wolves, jackals), racoon, bats, skunks, cats, bats, mongoose
without vaccine no detectable immune response until encephalitis symptoms emerge
too late to tx once there are symptoms :cry:
neutralising Abs detectable in sera approx 7 days + in CSF a bit later
rise to high levels terminally or in v rare survivors
in some patients no Ab is detectable
most of CSF Ab is thought to be produced intrathecally (in subarachnoid space)
if no vaccine, the likelihood of infection after a bite from a rabid dog = 35-57%
Furious rabies
hydrophobia (fear of drinking water)
aerophobia (fear of fresh air)
diaphragmatic contractions + possibly paralysis (resp arrest)
accessory resp muscular contractions + spasms
contractions often provoke by attempting to drink or air blowing on skin (Dx sign, esp in RLSs)
periodic excitement, hallucinations, aggression
lucid intervals
autonomic dysregulation: BP, temp, saliva
survival usually about 7 days
Paralytic rabies
less common than furious rabies
particular feature of vampire bat rabies
same prodromal symptoms, headache
flaccid ascending paralysis + paraesthesia
starts in affected limb, a/w pain
death from paralysis
but if supported in ICU, death tends to be from diffuse brain injury or arrhythmias
duration can be 2-3 wks
Transmission
virus in saliva of rabid animal: animal bites + licks are infectious
human-human: tears + saliva infectious
cornea transplant (8 cases)
MTC (1 case)
inhalation of aerosolised bad secretions in caves
Prodromal phase
in 33-45%
intense itch @ wound site
paraesthesia
non-specific: fever, headache, myalgias, sore throat, irritability, anxiety
3-7 days
Dx
Ag or Ab testing
Abs hard to interpret in vaccinated
viral isolation/culture/PCR
saliva
100% detection @ 0-4 days
50% @ 5-12 days
14% @ 13-16 days
resp secretions
CSF
tears
brain biopsy (usually post-mortem)
immunofluorescent staining of skin biopsy (neck) or corneal impressions
Dx won't alter prognosis
dDx
tetanus
can also follow a bite
shorter incubation period
persistence of muscle rigidity between spasms
absence of meningoencephalitis
encephalitis
no hydrophobia
poliomyelitis
no sensory symptoms
fever doesn't persist into paralytic phase