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ZOONOSESZOONOSES
dr. Muh. Nasrum Massi, Ph.D
Faculty of Medicine
Hasanuddin University
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Zoonoses
Transmission of the infectious agent
to humans from an ongoing reservoirlife cycle in animals, without the
permanent establishment of a new
life cycle in humansSpecies Jumping
The infectious agent derives from an
ancient reservoir life cycle in animals,but they have established a new life
cycle in humans that no longer
involves the animals
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Etiologic
Classifcation
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iral
!acterial
Parasitic
Mycotic
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Zoonoses" iral E#am$les
Colorado tick fever Japanese encephalitis
Ebola Monkeypox
Equine encephalitides(EE, EEE, !EE"
#ipah
$antaviruses %abies
$endra %ift !alley fever
$erpesvirus & est #ile virus
'nfluena )ello* fever
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Zoonoses" !acterialE#am$les
+nthrax lague
&rucellosis sittacosis
Campylobacteriosis - fever
Cat.scratch disease %elapsing fevers
/eptospirosis 0almonellosis/isteriosis Tularemia
/yme disease )ersiniosis
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Zoonoses" ParasiticE#am$les
PROTOZOAL !L"#$T#%
Trypanosomiasis &aylisascariasis
&abesiosis Cysticercosis
Cryptosporidiosis $ydatidosis
/eishmaniasis 0chistosome dermatitis
1iardiasis Trichinosis
Toxoplasmosis !isceral larva migransand toxocariasis
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Zoonoses" MycoticE#am$les
%s$er&illosis
!lastomycosis
'ry$tococcosis
Dermato$hytosis
Histo$lasmosisS$orotrichosis
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Zoonoses" %nimalS$ecies
2ogs 3 Cats
4 %abies
4 %ound*orm
4 %ing*orm
4 /yme 2isease (dogs only"
4 Cat 0cratch 2isease (cats only"
5ood +nimals 4 0almonella
4 E6coli
4 &rucellosis
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Zoonoses" %nimalS$ecies
&irds' 4 Psittacosis
4 (est $ile
4 %ryptococcus Reptiles) *ish) +
Amphibians 4 Salmonella
4 "ycobacterium (ild Animals
4 antavirus
4 Plague
4 Tularemia
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Routes o
TransmissionDirect( Dro$let or %erosol
( Oral
( 'ontact )ndirect
( Food*orne
( +ater*orne( Fomite
( ector*orne
( Environmental
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Diseases in Human
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Diseases Leptospirosis
Psittacosis
Anthrax Scrub typhus
Avian inuena
Rabies !SE "!ovine s$on&iform
ence$halo$athy-
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EP/OSP)0OS)S
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e$tos$irosis is an acute anthro$o1oonotic infection
)t occurs in tro$ical, su*tro$ical andtem$erate 1ones.
+eil Disease, Hemorrha&ic 2aundice, Mud Fever, S3ineherdDisease,'anicola Fever, sevenday
fever found commonly in 2a$an,'ane cutter4s disease in %ustralia,0ice 5eld e$tos$irosis in )ndonesia, Fort !ra&& fever in U.S.%ndamanhaemorrha&ic fever6%HF-
iN/0ODU'/)ON
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E$idemiolo&y
!ndemicLocations where the infection is
commonplace) caused by high rainfall) close
human contact with livestoc, or wild animals)
poor sanitation or wor,place e-posure .ricefarming) etc/0
1eneral
Locations where the infection is at the
international average of 2023 cases per422)222) and infection is usually the result of
accidental e-posure through wild rats)
livestoc, or direct contact with water through
leisure or occupation0
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/he reservoirs for Leptospira s$ecies include a 3ide ran&e of
3ild and domestic animals thatmay remain asym$tomatic
shedders for years.
Leptospira or&anisms e#creted inanimal urine, amniotic 7uid, or$lacental tissue are via*le in soil
or 3ater for 3ee8s to months.
Humans *ecome infected throu&h contact of mucosal surfaces ora*raded s8in 3ith contaminated
soil, 3ater, or animal tissues.
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People who are predisposed by
occupation include abattoir and sewerworkers, veterinarians, farmers, andmilitary personnel.
Recreational exposures and clusters of
disease have been associated withwading, swimming (especiallyswallowing water), or boating in
contaminated water,
particularlyduring flooding. Person-to-persontransmission is rare.
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Etiology
/eptospirosis is caused by spirochetes of
the genus Leptospira6
/eptospires are classified into a number of
species
defined by their degree of geneticrelatedness as determined by 2#+
reassociation6
There are 78 named pathogenic and
nonpathogenic species6 The genome sequence of Leptospira
interrogans serovar /ai has been
determined
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The genera Leptospira contains threespecies namely L interrogans) L
biflexa and L parv a0 4 The first includes 56 serogroups and
more than 532 serovars and is theprincipal cause of leptospirosis inhumans and animals0 most commonbeing L. canicola, L. hardjo and L.hebdomadis.
Two types of leptospirosis' 4 Anicteric leptospirosis or self7limited
illness .839 to :29 of the cases/ 4 #cteric leptospirosisor weil;s
syndrome .39 to 429 /
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#t is a thin spiral organism $%&mmx ' ( )$mm* +ith tightly set coils
#t is characterie, by very activemotility* by rotating "-spinning./
an, ben,ing% 0sually one or bothen,s o this single(cell organismare bent or hoo1e,
!ecause o their narro+ ,iameter*the leptospires are bestvisualie, by ,ar1(fel,illumination or phase contrastmicroscopy an, they ,o not stainrea,ily +ith aniline ,yes%
Leptospira interrogans
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A microscopic vie+ oLeptospira# bacteriastaine, apple green +ith auorescent ,ye "rom the
C2C3s Public 4ealth #mage
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Reservoirs
Wild and domestic animals rodents,
livestock (cattle, horses, sheep, goats,
swine), canines, and wild mammalsare the reservoir for leptospirosis.
Many animals have prolonged
leptospiruria without suffering fromthe disease themselves.
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Modes of Transmission
By direct or indirect contact of nasal, oral, oreye mucosal memranes or araded or
traumati!ed skin with urine or carcasses of
infected animals.
"rine# $ndirect e%posure through water, soil,or foods contaminated y urine from infected
animals is the most common route. &fter a
short period of circulating high levels of the
spirochete in their lood, animals shed the
spirochete in their urine, contaminating the
environment.
$nhalation of droplet aerosols of contaminated
fluids can occasionally occur
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$ncuation period
The incuation period is usually '
' days, ut usually (* + ' days)days.
-eriod of ommunicaility or $nfectious
-eriod /umans with leptospirosis usually
e%crete the organism in the urine for0 weeks and occasionally for
as long as 1 weeks.
-ersontoperson transmission isconsidered e%tremely rare.
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2irect &ssay
2emonstration of leptospires or
their products#
Microscopy 2arkfield microscopy
-hase contrast microscopy
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$ndirect &ssay
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2emonstration of a rise in antiody levelseither through M&T or 34$5& is essential
y repeating the sampling at least fourdays after taking the first sample.
$n hennai, the M&T test is availale at the6eterinary "niversity, Madhvaram, theM7R Medical "niversity, 7uindy and themicroiology department of the MadrasMedical ollege.
The $gM dip stick 34$5& is commerciallyavailale from 8rganon Teknika ($nfar
$ndia) and -an Bio (&ustralia). "sing thistest could help detect leptospirosis duringthe acute (early) phase of the illness.
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TREAT5E6T
Penicillin ' million units,aily #%7 "&$(&8 ,ays/
Amoxycillin* Erythromycin*9 2oxycycline
Patients +ith 5:;"5ulti
organ ailure/ to beobserve, an, treate, inintensive care unit
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-R3639T$89
3nvironmental Measures To prevent illness, prevent contamination of living, working
and recreational areas y urine of infected animals.
ontrol rodent populations in areas of human haitation.
2omestic animal owners should take necessary precautionsto minimi!e their animal:s potential contact with wildlife
( e.g., do not feed pets outside or allow animals to roam
unsupervised).
2o not allow animals to urinate in or near ponds or pools.
;eep animals away from gardens, playgrounds, sando%es,
and other places children may play.
&mong domesticated animals, vaccination of swine, cattle,
and dogs.
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Protected water supply to all0 Proper collection) transport) treatment
and secured disposal of garbage0
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Sinonym:fowl plague, fowl pest, peste aviaire, geflugelpest,
typhus exudatious gallinarium, Brunswick bird plague,Brunswick disease, fowl disease, fowl or bird grippe.
“ Suatu penyakit menular yg disebabkan oleh virusinfluenza subtipe !"#$ yg menyerang manusiadgn ge%ala demam & '(o), batuk, pilek, nyeri otot,nyeri tenggorokan dan pernah kontak dgn binatang tsbdlm * hr terakhir+
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amily: -rthomyxoviridae Btk filament virion diameter (./$0. nm uman !nfluen"a viruses# $,%,&
$vian !nfluen"a# limited to !nfluen"a $ viruses
INFLUENZA VIRUS
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1apat menyerang: / multiple species
2manusia, burung, kuda, babi, paus dll3
/ burung: vian influenza viruses
Beberapa subtipe menurut %enis !emaglutinin 2!3 dan
#euraminidase 2#3
$4 ! dan 5 #
6anusia: Subtipe !$#$, !0#0, !'#0
Burung: Semua subtipe
7aling virulen dibanding influenza B dan )
Virus Influenza A
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Avian Influenza A virus
"enginfe,si Tr0 Resp dan Tr0 1# burung' Biasanya tidak menyebabkan penyakit pada 8tik liar
Sering ter%adi genetik recombinant
6enyebabkan kesakitan dan kematian pada ternak
Avian influen?a virus ber,umpul @uga dalam feses
Bisa survive pd suhu rendah dan kelembaban rendahBisa hidup di air 9 hr 00o) a ' hr o)
6ati pd pemanasan "4o) ' %am a 4o) ' menit
1isinfeksi lingk sekitar diperlukan 2formalin a iodine3
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ward for influenza patients during $5$( pandemic
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)ontinues evolving of !"#$
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&linical 'pecimens for !nfluen"a
estingRespiratory
asal swap
asal wash
asal aspirate
asalpharyngeal swab *aintain &old &hain
'puta
hroat swab
racheal aspirate
+ther
'erum
Rectal swab
http#www.who.intcsrdiseaseavianinfluen"aguidlineshumanspecimensen
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aboratory precaution /0 esting
ighly pathogenic avian influen"a $ (/0) virus is classified as a selectagent and must be worked with under %iosafety level (%') 1 withenhancements conditions
&ontrolled access double door entry with change room and shower 2se of respirators 3econtamination of all wastes 'howering out of all personel 4ork with influen"a $ (/) suspected specimen must be separate from other
human influen"a $ (i.e., 0 or 1) virus work 3ue to the %' 1 5 re6uirements, respiratory virus cultures should not be
performed in most clinical laboratories and cultures should not be conducted
for patients suspected of having influen"a $ (/0) virus infection
http#www.who.int.csr.diseaseavianinfluen"aguidelineshandlingspecimens
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/0 3iagnosisRapid influen!a diagnostic tests
7 Results obtained within 0/-18 min
7 ot particularly sensitive
7 ot specific9 often miss avian :$; viruses
3etection of /=9 virus#
7 R-P&R in %'< conditions7 =iral isolation in %'1 enhanced lab conditions
> Results within =iral isolation the :gold standard;
3etection of antiody to /=9 virus
7 *icro-neutrali"ation assay using live /0 virus in %'1
enhanced lab conditions
7 &onfirm with 4estern %lot
7 'tandard influen"a ! antibody assay neither sensitive nor
specific9 produces false results
2iagnostics for $nfluen!a2iagnostics for $nfluen!a
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?merging !nfectious 3iseases,
08#@ Auly
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!nterpretation of Rapid est Results for
'uspected $vian !nfluen"a $ (/0)
egative result does not D o /0 infection#
> Calse negative (/0 detected by other tests)
> rue negative (no influen"a $ virus infection)Positive result does not D /0 infection#
Calse Positive
7 on-specific binding
7 !nfluen"a %
rue Positive (00, 0
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Molecular $dentification
of /=9
=iral R$ extraction
Reverse transcriptase of viral genome
$mplification of specific conserved region by
Polymerase &hain Reaction (P&R)
Eel-based detection of P&R amplicons
Real-time R-P&R (rR-P&R) Eene se6uencing
Phylogenetic mapping of viral isolates
$ t t ti f RT -R R lt$ t t ti f RT -R R lt
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he R-P&R assay result interpreted when# 7 he negative control reactions is negative
7 he positive control reaction is positive$ negative result is not necessarily definitive.
'uggests that influen"a virus genetic material
was absent from the sample tested
$ positive results based upon band side is
presumptive until proven by se6uencing
$nterpretation of RT-R Results#$nterpretation of RT-R Results#
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'ummary of aboratory
ests for !nfluen"a estingest arget 'pecimen 'ensitivity 'pecivicity ime
R-P&R R$ 'wabs,issue
55555 55555 F/ hr
=iralisolation
=irus 'wabs,issue
55555 55555 1-/ day
Rapid
est
$ntigen 'wabs 55 55 F0hr
! $ntibody 'era 555 5555 BG hr
*icro
ext
$ntibody 'era 5555 55555 @< hr
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gbr
7 'hipping permits are in order'hipping permits are in order
7 samples packed according tosamples packed according to
!nternational regulations!nternational regulations
7 =ials labeled=ials labeled
7 Hey of samples includedHey of samples included
7 racking information providedracking information provided
7 6uestionnaires have been filled in, list6uestionnaires have been filled in, list
of specimensof specimens
Time line for &nalysis and
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gbr
Time line for &nalysis and
Reporting /=9 ases
5ample ollection
5ample
5hipment
hrs
4aoratory
-rocessing>$nitial $2
'0 hrs
5hipment to W/8
Reference enter
'
weeks
haracteri!ation
Reporting
M8/,
W/8
Time 4apse#
' Weeks
'0 hrs
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hallenges in the 4aoratory
2iagnosis of /=9
?ducation of hospital and clinical staff &onsistent 6uality sampling
*aintaining sample cold chain &orrect keying of samples imely analysis of samples $ssay standardi"ation
3atabase maintenance &onfirmation of results ?ducation of health officialspublic
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P&R Materials re?uired
7 I!$amp =iral R$ *ini Hit or e6uivalent extraction kit7 I!$E? +ne'tep R-P&R kit
7 Rase inhibitor ($%!)
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;ips for cooking
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;ips for cookingpoultry
Separate raw food from cooked food
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!ovine s$on&iformence$halo$athy
:*ad &ow 3isease;
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Introduction
B53 is a fatal, neurodegerative disease in cattle,
that causes a spongy degeneration in the brain and
spinal and progressive degeneration of the nervous
system.
%'? has a long incubation period is about ervousness and aggression
> !ncoordination
> 3eath
o antemortem test
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!nfectious agent of %'? is believed to be a specifictype of misfolded protein called a prion
%ovine spongiform encephalopathy (%'?) is one ofseveral transmissible spongiform encephalopathies('?) diseases.
+r Prion diseases, which are progressive
neurological disorders thought to be caused byconversion of endogenous, host-encoded prion
protein (PrP) to an abnormal conformationdesignated PrPsc.
hose prion proteins carry the disease betweenindividuals and cause deterioration of the brain
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9:
+rigin of %'?
'till unclear, but $ppears to have originatedfrom scrapie, an endemic '? recogni"ed
since mid-0Gth
c.Rendered carcasses of livestock (includingsheep) fed to cattle as protein-richnutritional supplement
!n 0LG8, change in rendering processallowed etiologic agent to survive
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9;
&attle were infected through ingestion
&attle carcasses were recycled throughrendering plants, amplifying the cattle-adapted pathogen
Cirst verified case of %'? in the 2H in0LGM9 outbreak peaked in 0LL1
!n the end
> N 0G8,888 infected cattle > 'laughter of B./* cattle N18 months old
Eti l l f T i ibl S if
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Etiologycal of Transmissible Spongiform
Encephalopathies (TSEs)
$n unconventional virus
$ virino or OincompleteO viruscomposed of naked nucleic acid
protected by host proteins !nfectious fatal neurodegenerative
disorders
ransmissible agent unknown
*ost widely accepted theory is that'?s are caused by a modified form of
a normal cellular glycoprotein called a
prion protein
#ormal grey matter (co*"
!acuoliation of the
grey matter (co*"
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$ prion or abnormal proteinase resistant
protein, devoid of nucleic acid, capable of
causing a cell to produce more abnormal protein
Eenetic relationship to susceptibility
&ause no detectable immune or inflammatoryresponse in the host
ighly resistant to heat, ultraviolet light,
ioni"ing radiation, and common disinfectantsthat normally inactivate viruses or bacteria
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Prions
3efinition
Prions are single molecules containing
about
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?lectron *icroscopy of a Prion#
:ubulofilamentous particles
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'maller than most viral particles
!EK resistant to heat, 2= light,ioni"ing radiation, disinfectants
&auses no detectable immune or
inflammatory response
as not been observed microscopically
ittle is known about prion infectivity in
peripheral tissues.
Th N l i (P P )
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The Normal protein (PrP c )
is called PrP& (for cellular)
$ glycoprotein normally found at the cell surface
inserted in the plasma membrane has its secondary
structure dominated by alpha helices (probably 1of them)
?asily soluble
?asily digested by protease
?ncoded by a gene designated (in humans) PRP
located on our chromosome
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PrPSc
he abnormal, disease-producing protein
!s called PrP'c (for scrapie)
as the same amino acid se6uence as the normal
protein9 that is, their primary structures are
identical but
!ts secondary structure is dominated by beta
conformation !nsoluble in all but the strongest solvents
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ighly resistant to digestion by proteases
4hen PrP'c comes in contact with PrP&, it
converts the PrP& into more of itself (even in the
test tube).
hese molecules bind to each other formingaggregates.
!t is not yet clear if these aggregates are
themselves the cause of the cell damage or are
simply a side effect of the underlying disease process.
wo forms of prion# from PrPc to PrP'c
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wo forms of prion# from PrPc to PrP'c
The normal, membrane.associated protein (rc" can change its shape
to a harmful,disease.causing 3 highly aggregated form (r0c"6 Theconversion from rc to r0c then proceeds via a chain.reaction6 hen
enough r0c proteins have been made they form long filamentous
aggregates that gradually damage neuronal tissue6 The harmful r0c
form is very resistant to high temperatures, 9!.irradiation and strong
degradative enymes6
St t l Ch f i
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Structural Change of prion
protein
#ormal +bnormal
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ocali"ation of 3ifferent Prion 3iseases
#n fatal familial insomnia .**#/)
mutated prions accumulate in
the thalamus, *ith the result
that the patients are unable to
sleep6 #n %reut?feldt7Ja,ob disease
.%J
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Animal Transmissible Spongiform Encephalopathies
'crapie in 'heep and Eoatts
ransmissiblle *ink ?ncephallopatthy (*?) in
*ink &hroniic 4asttiing 3iisease (&43) in 3eer and
?llk
%oviine 'pongiiform ?ncephallopatthy (%'?) in
&attttlle,, &atts,, Hudu,, and yalla
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Process of Prion Hill in the %ody
Prion protein are found in all mammals. heirfunction is not fully understood but there are large
numbers of them in the brain, especially on the
surfaces of cell membranes.
$ccording to the prevailing theory, abnormally
folded prion proteins, make the normal proteins
refold into disease, causing shapes.
he normal proteins refold, taking on abnormalshapes.
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he newly refolded proteins interact with other
prion proteins, causing them to refold, too.
he altered proteins are resistant to breakdown
and may accumulate into pla6ues,
Prions on cell surfaces allow too much fluid to
enter cells, producing a spongey appearance
when cross-sections of brain tissue are
examined under a microscope.
*odels for prion disease process
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*odels for prion disease process
Prions in the body
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Prions in the body
hysical +ttributes of the affected brain:
4 Enlarged astrocytes. 0tar shaped
cells attached to blood vessels in
brain6
4 $oles *here neurons used to be6
4 +myloid laques.flo*er shaped
protein *axy buildup6
5ound in mainly in the brain, spinal cord and nervous tissue, *ith
increasing research discovering prions in glands and blood as *ell6
&0E &rain
0crapie &rain
Route of -rion
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&0E results *hen a
sufficient number of
nerve cells have
become damaged,
affecting the behaviorof the co*s
Route of -rion
$nfection
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ransmission
%'? can be transmitted from mother to fetus, as well as
from bull sperm to the female.
$lso contracted when infectious agent (prion) is ingested
in food.
&alves are fed a :baby formula; made from bovine blood
because it it much less expensive than milk, not to mention
the comparative resale values of the two li6uids
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%'? of &linical 'ymptoms
&hanges temperament (nevrousness or
aggression)
$bnormal posture !ncoordination and difficulty in rising
3ecreased milk production
oss of body conditioning
o change in appetite early in the disease
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3iagnosing %'?
&urrently the only sure way to diagnose %'? is to
look at the brain
> his means you have to kill the animal
'ectiions of the brain are prepared and examiined
under the microscope looking for the
characteriistiic :spongy; change
'pecial stains can also be used to identiify thefibrils formed by the abnormal prion protein
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&urrently there is no test that can be
performed on the live animal
*any researchers are trying to develop such
a test2sing laboratory tests, it is possible to
distinguish between the different forms of
'?
his means it is possible to distinguish %'?
from scrapie and from &43
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2iagnosis of microspoce
,r% 5uh% 6asrum 5assi*
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0a*ies0a*ies
Ph%2
+h t i 0 *i+h t i 0 *i
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0a*ies is a disease0a*ies is a disease
that a
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/he ra*ies virus can /he ra*ies virus can&et into your *ody&et into your *ody
and attac8 yourand attac8 yourcentral nervouscentral nervoussystemsystem
+atch as the ra*ies+atch as the ra*iesvirus from anvirus from ane#$osure on the le&e#$osure on the le&s$reads u$ the s$inals$reads u$ the s$inal
cord to the *rain andcord to the *rain andthrou&hout the restthrou&hout the restof the *odyof the *ody
)nterestin& facts a*out)nterestin& facts a*out
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)nterestin& facts a*out)nterestin& facts a*out
ra*iesra*ies
7;,
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'ommon'ommon
'arriers'arriershe raccoon is thehe raccoon is themost commonmost common
carrier B8.Mcarrier B8.M
'kunk
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=ind of animals &et ra*ies=ind of animals &et ra*ies
The rabies virus can infect allThe rabies virus can infect all
mammals .dogs) cats/0mammals .dogs) cats/0
"ammals are warmblooded"ammals are warmbloodedanimals that have hair andanimals that have hair and
mammary glands to producemammary glands to produce
milk for their babies6milk for their babies6 +nimals like frogs, birds, and +nimals like frogs, birds, and
snakes do not get rabies6snakes do not get rabies6
/ i i/ i i
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/ransmission /ransmission
The commonest *ay of rabies transmissionThe commonest *ay of rabies transmissionis by the bite of an infected mammalis by the bite of an infected mammal
&ites by rabid animals generally inoculate virus.&ites by rabid animals generally inoculate virus.
laden saliva through the skin into muscle andladen saliva through the skin into muscle and
subcutaneous tissuessubcutaneous tissues
%abies virus entry occurs through *ounds or%abies virus entry occurs through *ounds or
direct contact *ith mucosal surfaces6 Thedirect contact *ith mucosal surfaces6 The
virus cannot cross intact skinvirus cannot cross intact skin %abies can be transmitted by moisture%abies can be transmitted by moisture
droplets in the air (aerosol"droplets in the air (aerosol"
Rabies ife &ycleRabies ife &ycle
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Dunne ')DPDunne ')DP 2anuary ;>, ? 2anuary ;>, ?:
Rabies ife &ycleRabies ife &ycle
7irusinoculation
"bite/
Salivaryglan,
excretion
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RA!#ES L#;E C
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0a*ies iruses0a*ies iruses The family %habdoviridaeThe family %habdoviridae generagenera
LyssavirusLyssavirus
StructureStructure%abies virus is a rod. or bullet.shaped,%abies virus is a rod. or bullet.shaped,single.stranded, negative.sense,single.stranded, negative.sense,
unsegmented, enveloped %#+ virus6 Theunsegmented, enveloped %#+ virus6 The
virus genome encodes five proteinvirus genome encodes five protein
associated *ith either the ribonucleoproteinassociated *ith either the ribonucleoprotein
(%#" complex or the viral envelope(%#" complex or the viral envelope
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Phatogenesi
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%abies virus may enter the peripheral%abies virus may enter the peripheralnervous system directly, or may replicatenervous system directly, or may replicatein muscle tissue after entering the host,in muscle tissue after entering the host,remaining at or near the site ofremaining at or near the site of
introduction for most of the incubationintroduction for most of the incubationperiod6period6
The precise sites of viral sequestrationThe precise sites of viral sequestration
remain unkno*n, since neither antigenremain unkno*n, since neither antigennor virus can usually be found in anynor virus can usually be found in anyorgan during this phaseorgan during this phase
Phatogenesi
s
PATHOGENESISPATHOGENESIS
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PATHOGENESIS PATHOGENESIS
Live virus Live virus Epidermis, Mucus membrane Epidermis, Mucus membrane
Peripheral nerve Peripheral nerve
CNS ( ra! ma""er #CNS ( ra! ma""er #
O"her "issue (salivar! lands,$#O"her "issue (salivar! lands,$#
cen"ripe""all!
cen"ri%uall!
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Sym$toms in humansSym$toms in humans
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Sym$toms in humansSym$toms in humans
Sym$toms occur A: to B: days afterSym$toms occur A: to B: days afterthe *ite.the *ite.
Early sym$toms include fever,Early sym$toms include fever,
headache, sore throat and feelin& tired.headache, sore throat and feelin& tired.
)f the virus &ets to the *rain the $erson)f the virus &ets to the *rain the $erson3ith it mi&ht act nervous, confused,3ith it mi&ht act nervous, confused,
and u$set.and u$set.
Other sym$toms" $ain or tin&lin& in theOther sym$toms" $ain or tin&lin& in the
s$ot 3here the $erson 3as *itten,s$ot 3here the $erson 3as *itten,
hallucinations, hydro$ho*ia, andhallucinations, hydro$ho*ia, and
$aralysis.$aralysis.
5ive general stages of rabies are recognied5ive general stages of rabies are recognied
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in humansin humans::
776 'ncubation6 'ncubation
> Typically '@+A@ daysTypically '@+A@ days
> (0 days to C years)(0 days to C years)
> 2ose, location, variant, host factors2ose, location, variant, host factors
==00 rodrome phaserodrome phase (malaise, vomiting, sore throat,(malaise, vomiting, sore throat,paresthesia at site of bite"paresthesia at site of bite"
8686 +cute neurologic period : +cute neurologic period : sensory phasesensory phase
(ympathetic overactivity, salivation, perspiration,(ympathetic overactivity, salivation, perspiration,spasm of the throat muscle: hydrophobiaspasm of the throat muscle: hydrophobia
>6>6ComaComa (excitement", and(excitement", and
;6;6 aralytic or depressivearalytic or depressive ? death? death
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hy,rophobia excitement
&IAGNOSIS &IAGNOSIS
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74aoratory finding# ( 5< )4aoratory finding# ( 5< )73%clusion of other etiologies3%clusion of other etiologies
7-athology#-athology#
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&IAGNOSIS &IAGNOSIS
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7 Is'la"i'n '% virus (saliva,CS, brain # Is'la"i'n '% virus (saliva,CS, brain #
7 Ser'l'! Ser'l'!
7)iral A de"ec"i'n ( in%ec"ed "issue #)iral A de"ec"i'n ( in%ec"ed "issue #
7)iral &NA de"ec"i'n ( PC* #)iral &NA de"ec"i'n ( PC* #
Prevention Prevention
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Preventionevention1ive your household pets vaccinations1ive your household pets vaccinations
regularly6 't *ill prevent your pet fromregularly6 't *ill prevent your pet fromgetting rabies from *ild animals6getting rabies from *ild animals6
+void *ild animals acting abnormally6 +void *ild animals acting abnormally6
+nti.rabies shots can prevent the disease6 +nti.rabies shots can prevent the disease6 4 +t first, 7.8 shots of antibodies are given +t first, 7.8 shots of antibodies are given
around the bite6around the bite6
4 Then, five shots of vaccine are given in theThen, five shots of vaccine are given in thearm over 8< days6arm over 8< days6
4 %abies shots help your body make po*erful%abies shots help your body make po*erful
antibodies that kill the virusantibodies that kill the virus
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he +rganism $gent
/he Or&anism
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&
Psittacosis is "oonotic infection caused by
Chlamydophila psittaci
amily Chlamydiaceae
Chlamydophila psittaci, formerly named Chlamydia
psittaci
Eram negative
+bligate intracellular bacteria
$ir-born spread (birds faeces)
arget cells# macrophages, lung parenchyma
Structure C psittaci
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Structure C. psittaci
?nergy ($P) parasite bacteria with uni6e
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biphasic life cycle
he developmental cycle includes two formare ?lementary body (?%) and Reticulate body(R%)
he bacteria that causes endemic avianchlamydiosis, epi"ootic outbreaks inmammals, and respiratory psittacosis inhumans.
&hlamydiaceae are well adapted for survivaloutside of the host and for persistence in ahost.
&omparison of ?% and R%
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&omparison of ?% and R% ?lementary body (?%)
> he extracellular form survival
> !nfectious and toxic for mice
> !t is smaller than the reticulate body (?% si"e 8,1 N m)
> he ?% is relatively resistant to sonication and trypsin
> he permeability of the ?% is low
> he R$ # 3$ ratio of the ?% is
approximately 0 # 0 > !nduces endocytosis and metabolicaly inactive
Reticulate body (R%)
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Reticulate body (R%)
> he reticulate body is the intracellular form and
8,/ > 0,8 N m > he reticulate body is not infectious and not toxic
mice
> he reticulate body is sensitive to sonication > he R% is permeable to metabolites
> he R$ # 3$ ratio of the R% is approximately
1 # 0
> !nduces no endocytosis
> *etabolicaly active
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$n elementary body of Chlamydophila psittica sho!ing theouter membrane (+*) and the cytoplasmic membrane (&*)
$nd the absence of a peptidoglycan layer. he peptoglycan
layer is also absent in reticulate bodies
Replication of C psittasi
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Replication of C" psittasi
?lementary bodies attach to the microvilli ofsusceptible cells
he ?%s are internali"ed in cytoplasmic
phagosomes9 fusion with lysosomes andkilling does not occur with viable ?%s
?%s change into reticulate bodies (R%)
Reticulate bodies are metabolically active
4ife cycle and method of
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infection
hey are able to synthesi"e# 3$, R$,
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y y , ,Protein, &ellular components
7 $re energy parasites that use $P produced bythe host cell
7 he reticulate bodies then convert back to
elementary bodies and are released back intothe lung, often after causing the death of thehost cell. he ?%s are there after able to infectnew cells, either in the same organism or in a
new host
ew axonomic
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&lassification &hlamydiaceae
• GenusChlamydia−
C. trachomatis−C. muridarum
−C. suis
• GenusChlamydophila−C. psittaci
−C. abortus
−C. felis
−C. pecorum
−C. pneumoniae
−C. caviae
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'erovar of & psittaci
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'erovar of &. psittaci
!dentification of serovar may help to determine
the source of infection
Chlamydophila psittaci has eight known
serovars#
> six have been primarily isolated in birds and
two strains have been isolated in mammals.
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C" psittaci serovar $ is endemic among
psittacine birds and has caused sporadic"oonotic disease in humans, other mammals
and tortoises.
'erovar % is endemic among pigeons, has beenisolated from turkeys, and has also been
identified as the cause of abortion in a dairy
herd.
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'erovars & and 3 are occupational ha"ards for
slaughterhouse workers and for people incontact with birds.
'erovar ? isolates have been obtained from avariety of avian hosts worldwide and outbreak
in humans, a specific reservoir for serovar ?
has not been identified.
he C psittaci
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he C" psittaci
Resistant to drying
> Remains infectious for months
> Remains viable on surfaces for 'urvives in turkey carcass for N0
year.
http://www.usda.gov/oc/photo/78c0509.jpghttp://www.usda.gov/oc/photo/78c0509.jpg
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?pidemiology
?pidemiology
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?pidemiology
+ccurs worldwide as sporadic disease
here are /8-088 confirmed cases
per year
> 0-< deaths
> rue incidence unknown
ationally reportable in humans
Pet store employees, bird owners, poultry
processing plant workers
Populations at Risk
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Populations at Risk
ab workers
=eterinarians
$vian 6uarantine
workers
Qoo workers
Carmers
Pregnant women
%ird fanciers
(pigeon fanciers too)
%ird owners
Pet shop employees
Poultry slaughter and
processing workers
4ildlife rehab workers
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ransmission
Transmission to /umans
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%irds are the reservoirs of the disease and the infection
is usually transmitted to humans #
> !nhalation
7 3ried infective droppings
7 'ecretions or dust fromfeathers
> *outh-to-beak
> 3irect contact
7 andling plumage or tissues of infected birds > Person-to-person transmission
7 ot proven and venereal transmission reported
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3isease in umans
Psittacosis
/uman 2isease of
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-sittacosis !ncubation period# 0-B weeksRange
> !napparent infection
> 'ystemic infection with pneumonia
7 Pneumonia 18-M8 years of age
&ommon signs > abrupt onset
> Cever, chills, headache, malaise, myalgia,
sore throat, cough, dyspnea, splenomegaly,
rash
Clinical Signs
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Psittacosis (ornithosis) usually is an acute febrilerespiratory tract infection with systemic symptoms
and signs that often include fever, nonproductive
cough, headache, and malaise.
?xtensive interstitial pneumonia can occur with
radiographic changes characteristically more severe
than would be expected from physical examination
findings.
g
+fter several days of untreated illness,
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lethargy and sluggish speech may be seen
*ith coma or stupor6 May also see : 4 Endocarditis, placentitis, myocarditis,
hepatitis, arthritis6 @eratoconAunctivitis,
and encephalitis Myocarditis, Aaundice, 4 %espiratory failure, thrombocytopenia, and
fetal death have been reported respiratory
failure6
4 Epistaxis and mucocutaneous
manifestations frequently occur
4 +rthralgia rare
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45 year old male, rail station worker with Chlamydial pneumonia
2iagnosis
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2iagnosis
&onfirmed case > &linical signs 5 laboratory results
7 &ulture from respiratory secretions
7 B-fold rise in titer 7 $ reciprocal titer of 0M of !g* detected by *!C
(microimmunofluorescence
Probable case
> inked epidemiologically to confirmed case of
Psittacosis
> 'ingle titer ≥0#1<
reatment and Prognosis
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reatment and Prognosis
4ith treatment
> 0-/ case-fatality rate
> etracyclines are drug of choice
> Remission of symptoms
7 2sually in BG-@< hours
> Relapse possible
4ithout treatment
> *ay resolve in few weeks-months
> 08-B8 case-fatality rate
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3isease in $nimals
Avian Chlamydiosis (AC)
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$vian &hlamydiosis
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$vian &hlamydiosis
&arriers may appear healthy
> 'hed intermittently
'hedding activated by stress > 'hipping, breeding crowding,
chilling
'hedding greatest in young birds
$vian &hlamydiosis
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$vian &hlamydiosis
!ncubation period
> 1 days to several weeks
atent infection > common
*orbidity and mortality
> vary with species and serotype
&linical 'igns in Pet %irds
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Center for 5ood 0ecurity and ublic $ealth
'o*a 0tate 9niversity . =
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Center for 5ood 0ecurity and ublic $ealth
'o*a 0tate 9niversity . =</ppin urkey, 3uck Pigeon/pp > 3epression
> Ruffled feathers
> 4eakness > !nappetence
> asal discharge
> Respiratory distress
> Kellow-green diarrhea
> &onSunctivitis
> 3ecreased egg production
> $taxia-pigeons
> rembling-ducks
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3iagnosis
3iagnosis
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g
3iagnosis difficult
&ase definitions
> &onfirmed, probable, suspect
'ingle test may not be ade6uate
> &ombination testing recommended
Proper sample collection techni6ues critical for
accurate results
&onsult an experienced avian veterinarian
3iagnosis
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g
Pathologic diagnosis
&ulture
$ntibody tests
> &C, ?%$
$ntigen ests
?!'$, !C$, P&R R!*
reatment for Pet %irds
http://www.nirgal.net/graphics/petri_dish.jpghttp://virology-online.com/general/CFT.gif
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*ay be difficult
Catalities occur
'upervised by licensed veterinarian in consult
with avian specialist
$ll birds treated B/ days
?ven with treatment
> atent infections can remain
> 'hedding may occur
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Prevention and &ontrol
Prevention and &ontrol
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?ducate and protect those at risk
> &lothing, gloves, cap, ?P$ filters
> 4et carcass with water and detergent prior to necropsy
3isinfect
> 0#0888 6uaternary ammonium compounds
> 0 ysol
> @8 isopropyl alcohol > 0#088 bleach
dr. Muh. Nasrum Massi, Ph.D
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%N/H0%C
!ntroduction
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$ diseases caused by #acillus anthracis spores
uman "oonotic disease
> 'pores found in soil worldwide
> Primarily a disease of domesticated wild animals
7 'heep, goats, cattle, cows, horses, goats
7 *any large documented epi"ootics
> +ccasional human disease
7 ?pidemics have occurred but uncommon7 Rare in developed world
atural reservoir is soil
3oes not depend on an animal reservoir making it
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> 3oes not depend on an animal reservoir making ithard to eradicate
> &annot be regularly cultivated from soils wherethere is an absence of endemic anthrax
> +ccurs sporadically throughout 2'
> 'outh 3akota, $rkansas, exas, ouisiana,*ississippi, &alifornia recogni"ed endemic areas
$nthrax "ones
> 'oil rich in organic matter (p F M.8)
> 3ramatic changes in climate
E$idemiolo&y
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*ay be spread by streams, insects, wild animals, birds,contaminated wastes
$nimals infected by soilborne spores in food water or bitesfrom certain insects
umans can be infected when in contact with flesh, bones, hides,hair, excrement
> nonindustrial or industrial
> cutaneous inhalational most common
Risk of natural infection 0088,888
> +utbreaks occur in endemic areas after outbreaks in livestock
?pidemiology
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p gy
uman cases > historical risk factors
> $gricultural
7 ?xposure to livestock
> +ccupational
7 ?xposure to wool and hides
7 4oolsorterTs disease D inhalational anthrax
7Rarely laboratory-ac6uired
#acillus anthracis
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Eram 5 rod Cacultative anaerobe 0 - 0.
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'porulation re6uires
> Poor nutrient conditions > Presence of oxygen
'pores (dehydrated cells) > 'urvive for decades > aken up by host and
germinate
> ighly resistant to heat, cold,
chemical disinfectants, dry periods
ethal dose /.< million bp
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> $mes strain se6uenced
< plasmids > px80
7 0GB kbp
7 Pathogenicity island
> pV8<
7 L/.1 kbp7 &apsule
$nthrax receptor
> +ccurs N than ten thousendfold
on macrophage cell
> $R?*G gene7 &hromosome B
Patho&enesis
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he infectious dose of #" anthracis in humans by any route is not
precisely known.
> Rely on primate data
> *inimum infection dose of W0,888-G,888 spores
> 3/8 of G,888-08,888 spores forinhalation
=irulence depends on < factors
> &apsule
> 1 toxins
&apsule
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Elycocalyx
> 'ticky, gelatinous polymerexternal to cell wall
pV8< plasmid *ade up of 3-glutamic acid
on-toxic on its own +nly encapsulated #" anthracis
virulent *ost important role during
establishment of disease > Protects against phagocytosis lysis during vegetative state
/o#ins pV80 plasmid
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pV80 plasmid
$% model
> %inding
> $ctivating
Protective antigen (P$), edema factor (?C) lethal factor (C)
> *ake up /8 of proteins in theorganism
!ndividually non-toxic
> P$5C lethal activity
> ?C5P$ edema
> ?C5C inactive
> P$5C5?C edema necrosis9lethal
htt$"333.rcs*.or&$d*molecules$d*?>;.html
/o#in Protective antigen (P$, G1k3a) > Pag gene
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> %inds to receptor helps internali"e
other < proteins ?dema factor (?C, GL k3a)
> Cya gene
> $denylate cyclase
> $ffects all cells
ethal factor (C, G@ k3a)
> $ef gene
> *ore important virulence factor
> *etalloprotease
> &leaves mitogen activated proteinkinase kinsase (*$PHH)
> $ffects only macrophages
Mehanis! of Infetion
$ h b d
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$nthrax spores enter body
Eerminate multiple in lymph nodes P$, ?C, C excreted from bacteria P$ binds to ?*G. P$ nicked by protease furin
> eptamer forms ?C andor C binds &omplex internali"ed by endocytosis $cidification of endosome
C or ?C crosses into cytosol via P$ mediated ion-conductivechannels C cleaves *$PHH 0 < ?C stimulates c$*P
Pathway of &ellular $nthrax
$ttack
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$ttack
&linical !nformation
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!nfection
'ymptoms (0st and
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he estimated number of naturally occurring human cases of
anthrax in the world is
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here are two phases of symptom.
0) ?arly phase - *any symptoms can occur
within @ days of
infection
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Cever (temperature N 088 degrees C) &hills or night sweats eadache, cough, chest discomfort, sore throat Aoint stiffness, Soint pain, muscle aches 'hortness of breath ?nlarged lymph nodes, nausea, loss of appetite,
abdominal distress, vomiting, diarrhea *eningitis
-
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%reathing problems, pneumonia
'hock
'wollen lymph glands
Profuse sweating
&yanosis (skin turns blue)
3eath
hree clinical forms of$nthrax #
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&utaneous anthrax
> 3irect contact of spores on skin
> *ost common (L/)
> 'pores enter to skin through small lesions
!nhalation anthrax > 'pores are inhaled
> rare (F/)
> *ost likely encountered in bioterrorism event
Eastrointestinal (E!) anthrax > 'pores are ingested
> +ral-pharyngeal and abdominal
*ortality
> !nhalational GM-088 (despite treatment)
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( p )
7 ?ra of crude intensive supportive care
> &utaneous F/ (treated) > E! approaches 088
!ncubation Period > ime from exposure to symptoms
> =ery variable for inhalational
7
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ransmission > o human-to-human
> aturally occurring cases
7 'kin exposure7 !ngestion
7 $irborne
> %ioterrorism
7 $erosol (likely)7 'mall volume powder (possible)
7 Coodborne (unlikely)
ypes three of anthrax infection
occur in humans#
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0) &utaneous
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when the bacterium enters a cut or
scratch on the skin due to handlingof contaminated animal productsor infected animals.
*ay also be spread by bitinginsects that have fed on infectedhosts.
$fter the spore germinates in skintissues, toxin production initiallyresults in itchy bump that develops
into a vesicle and then painless black ulcer.
htt$"science.ho3stu
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he most common naturally occurring form ofanthrax.
2lcers are usually 0-1 cm in diameter.
!ncubation period#
> 2sually an immediate response up to 0 day
&ase fatality after < days of infection# > 2ntreated ( 4ith antimicrobial therapy (0)
&utaneous $nthrax
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C2C, Cutaneous +nthraxB!esicle 2evelopment
!nhalation $nthrax
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he infection begins with the
inhalation of the anthrax spore.
'pores need to be less than /microns (millionths of a meter) toreach the alveolus.
*acrophages lyse and destroysome of the spores.
'urvived spores are transported tolymph nodes.
$t least
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3isease immediately follows
germination.
'pores replicate in the lymph nodes.
he two lungs are separated by astructure called the mediastinum,
which contains the heart, trachea,esophagus, and blood vessels.
%acterial toxins released duringreplication result in mediastinalwidening and pleural effusions
(accumulation of fluid in the pleuralspace).
!nhalation $nthrax
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3eath usually results
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E! anthrax may follow afterthe consumption ofcontaminated, poorlycooked meat.
here are < different formsof E! anthrax#
0) +ral-pharyngeal
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+ral-pharyngeal form - results from the deposition and
germination of spores in the upper gastrointestinal tract.
ocal lumphadenopathy (an infection of the lymph
glands and lymph channels), edema, sepsis develop after
an oral or esophageal ulcer.
$bdominal form - develops from the deposition and
germination of spores in the lower gastrointestinal tract,
which results in a primary intestinal lesion.
'ymptoms such as abdominal pain and vomiting appearwithin a few days after ingestion.
E! !nfection
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E! anthrax cases are uncommon.
here have been reported outbreaks in Qimbabwe, $frica andnorthern hailand in the world.
E! anthrax has not been reported in the 2'.
!ncubation period#
> 0-@ days
&ase fatality at < days of infection#
> 2ntreated ( 4ith antimicrobial therapy (undefined) due to the rarity
Pathophysiology
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18=#-S8S Eram stain
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Eram stain
&ulture of #" anthracis from the blood, skin lesions,vesicular fluid, or respiratory secretions
V-ray and &omputed omography (&) scan
Rapid detection methods
- P&R for detection of nucleic acid
- ?!'$ assay for antigen detection
- +ther immunohistochemical and immunoflourescenceexaminations
- hese are available only at certain labs
Eram 'tain $nalysis
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2seful for cutaneous and
inhalation anthrax.
$ blood sample or skinlesion is taken from the patient and cultured for M to
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2seful for inhalation and E!
anthrax
&hest V-rays is advised as aninitial method of inhalationanthrax detection, but it issometimes not useful for patientswithout symptoms.
Cind a widened mediastinum and pleural effusion.
Picture shows widened
mediastinum caused by #"anthracis infection % resulting lessavailable space in lungs
'nhalation +nthrax, 'ntroduction, 2%, +rmed 5orces 'nstitute of athology
At day 4At day 4 At day 6At day 6
); scan
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2seful for inhalation and E! anthrax ?ven when V-rays are negative, & scans may provide more precise
information. &hest & (Right) shows the increase in the si"e of the pleural effusions
(accumulation of fluid in the pleural space).
'nhalation +nthrax, 'ntroduction, 2%, +rmed 5orces 'nstitute of athology
P&R $ssay
P&R is a target amplification method of nucleic acid based
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P&R is a target amplification method of nucleic acid based
%. anthracis detection.
2sed for the detection of anthrax toxin genes.
ex) rpo% gene - used as a specific chromosomal marker forR-P&R detection.
he rpo% gene was se6uenced from 1M %acillus strains
he assay was specific for 0BB %acillus anthracis strains from
different geographical locations.
Provided 088 sensitivity and specificity
P&R $ssay 3etection time#
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3etection time#
- P&R only takes several hours
ex) Rapid-cycle R-P&R can be finished within 0-< hours
&an start early treatment of $nthrax
here are many different types of P&R assays for the detection of $nthrax
such as multiplex P&R, enterobacterial repetitive intergenic consensus-P&R
(?R!&-P&R), and long-range repetitive element polymorphism-P&R.
Rapid diagnostic methods provide answers in minutes or hours instead of
days.
reatment
%efore 'topped for fear of geneticallyengineered resistant strains
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M8 day course of antibiotics
&iprofloxacin > fluoro6uinolone
> /88 mg tablet every 0 M-deoxy-tetracycline
> 088 mg tablet every 0 clindamycin
> rifampin
> chloramphenico
=accine %iohrax$nthrax vaccine absorbed
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%iohrax$nthrax vaccine absorbed
> *ade by %ioport > Route of exposure not important $dministered subcutaneously
> ./m at 8,
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