Post on 13-Apr-2018
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Faculty of Allied Medical
Sciences
Clinical Immunology & Serology
Practice(MLIS 201)
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Typhoid fever
Prof. Dr. Ezzat M Hassan
Prof. of Immunology
Med Res Inst, Alex Univ
E-mail: elgreatlyem@hotmail.om
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eac!ing "#$ecti%es
• To define Typhoid Fever
• To know the causes and symptoms of the disease
• To understand how the bacteria cause the disease
• To know different methods to diagnose Typhoid fever • To define Widal test and its components
• To describe the procedure of tube Widal test
• To know how to interpret the results
• To describe the procedure of slide Widal test
• To know the causes of false +ve and flase –ve results
• To know the limitations of the test
4
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Countries endemic for typhoid(U.S. CDC 2006)
Alex Laointe! Wikimedia "ommons 5
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efinition
• An infectious feverish disease caused by the bacterium Salmonella typhiand less commonly by Salmonella paratyphi#
• The infection always comes from another human! either an ill person ora healthy carrier of the bacterium#
• ersons with typhoid fever carry the bacteria in their bloodstream andintestinal tract
• Transmitted through the ingestion of food or drink contaminated by thefeces or urine of infected people
•The bacterium can withstand both drying and refrigeration#
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Causes
1. Caused by the bacterium Salmonella Typhi .
2. Ingestion of contaminated food or water.
3. Contact with an acute case of typhoid fever.
4. Contact with a chronic asymptomatic carrier.
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Salmonella typhi
• Rod shaped, fageated, aerobic, !ram "ve bacii.
• Refrigeration and free#ing coud sow their growth.
• $asteuri#ing and food irradiation %i Salmonella for
commerciay"produced foodstuffs
• &oods prepared in the home from raw eggs can spread
samonea if not propery coo%ed before consumption.
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Ingestion of contaminated food or water
Salmonella typhi
Carried by white bood ces into the iver, speen, and bone marrow
'utipy and reenter the boodstream (Cinica iness)
*acteria invade the gabadder, biiary system, and the ymphatic tissue of thebowe and mutipy in high numbers
+hen pass into the intestina tract (can be identified for diagnosis in cutures
from the stoo)
Typhoid ulcers can cause perforation and hemorrhage
How does the bacteria cause disease ?
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How does the bacteria cause disease ?
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Sym'toms
• $o symptoms % if only a mild exposure& some people
become 'carriers' of typhoid#
• oor appetite! (eadaches and generali)ed pains!
• Fever! Lethargy
• *ose spots on chest wall
• iarrhea , constipation and abdominal pain• "hest congestion develops in many patients!
• slow heartbeat#
• -nlarged spleen and liver
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Rose spots High fever
Diarrhea
Typhoid Meningitis
Aches and pains
Chest congestion
Sym'toms
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iagnosis
iagnosis of ty'!oid fe%er is made #y
• "linical examination
• .lood! bone marrow! or stool cultures for S. typhi
• /erological Tests
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1.Detection of Antibodies in serum:
0#Widal test 1Tube or /lide2! 3#Typhidot assay
4#Tubex system! 5# ipstick assay#
2. Detection of Antigens in serum:
0# Tubex system 3# "ountercurrent 6mmunoelectrophoresis 1"6-2#
4# "o%agglutination test# 5# -L6/A
3. Detection of Antigens in urine:
0#Tubex system 3# "6-!
4# Latex agglutination 5# "o%agglutination
Serodiagnosis of y'!oid
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Widal testWidal test
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• Antigenic structure of Salmonella
H( agella ) antigensO (somatic)
antigens Vi (Virulence) a!sular
!olysaharideantigens
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" (somatic) antigens (flagella) antigens
• "P# in the ell $all%
• &eat sta'le
• "ess immunogeni
• Agglutination $ithantisera:
(ine, om!at, granularhal)y lum!s
Present in *agella% &eat la'ile%
#trongly immunogeni;Indue ra!id + &igh A'
titres%
Agglutination $ithantisera:
"arge, loose, otton$ool lum!s
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*i (%irulence) antigen
• a!sular !olysaharide ex!ressed on ertain seroty!es
• &eat la'ile%
• Poorly immunogeni, U anti'odies are !rotetive:1. Detection of Vi antibod not !el"ful in diagnosis
2. Absence in a case of t"!oid "oor "rognosis;
3. #ersistence of Vi antibod : carrier state
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• Tube agglutination test#
• etects anti 7 and ( antibodies in serum
• iagnosis of Typhoid and aratyphoid cases
• "arriers of typhoid bacilli possess antibody against
the 8i antigen of /# typhi# 18i tires seem to correlate
better with the carrier state than do 7 or ( titres2#
• For this reason! the use of 8i agglutination fordetection of carriers was suggested #
r.+.-.Rao ' 1
+IAL est
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Widal test
• /ignificance
6 st week negative#
Titers raise in 3nd week
*aise of titers is diagnostic
r.+.-.Rao ' 2/
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Materials
• Antigens9
0 /uspension of /# typhi '7' antigen! 7
0 /uspension of /# typhi '(' antigen& (
0 /uspension of /# paratyphi A '(' antigen! A
0 /uspension of /# schottmuelleri '(' antigen! .
• Antibody9 serum of suspected patient
• $ormal saline
• Test tubes and pipettes
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11 22 33 44 55 66 77
OO
HH
PAPA
PBPB
P,"C-.,-
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P,"C-.,-• :ake the mark of tubes
• ilute patient;s serum 090< 1<#0 ml serum + <#= ml saline2#• Add reagents as the following9
*eagent 1ml2 0 3 4 5 > ? @
/aline <#> <# > <#> <# > <# > <# > <# >
090< atient serum <#> <#> <#> <#> <#> <# > discard
/erum dilution 093< 095< 09< 090?< 0943< 09?5< %
.acteria suspension <# > <# > <# > <# > <# > <# > <# >
Final serum dil# 095< 09< 090?< 0943< 09?5< 0903< %ve
.acteria suspension9 7 ( A .
ha%e severa times, put it in 3ha%e severa times, put it in 3//C water bath for 1"1 hours.C water bath for 1"1 hours.
+hen et it stand at room temperature over night+hen et it stand at room temperature over night..
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"#ser%ation9
//o not s!ae tu#es #efore reading t!e results
0# "ontrol tube 1Tube $o# @29 no agglutination 1%2
3# Lowest titer tube9 absolutely agglutination 1++++2 4# 7ther tubes9
B agglutination1+++2 C agglutination 1++2
D agglutination 1+2 no agglutination 1%2
Inter'retation
Agglutination titer the highest dilution of serum
which appears 1++2 bacteria agglutination#
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Agglutination ho$ it a!!earsafter reativity
"
Feli tube
Round botto!
" agglutination
Co!pact
granular
agglutination
H
Dreyer#s tube
Conical botto!
H agglutination
$oose
Cotton woolly
clu!ps
/'served for agglutination:H : $oose % cotton &ooll clum"s; O : 'om"act ine granular
agglutination;
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o do you read +idal test results for
ty'!oid fe%er• The highest dilution of the patients serum in
which agglutinations occurs is noted! ex# if the
dilution is 0 in 0?< then the titer is 0?<#
• Agglutination in dilution up to E09?< is seen
in normal individuals # Agglutination in dilution
090?< is suggestive of /almonella infection#
• Agglutination in dilution of 0943< is
confirmatory of -nteric fever #
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Interpretation of results
!1"#0$ %!1"160$!1"#0$ %!1"160$
&%!1"#0&%!1"#0
'orm() *()ue'orm() *()ue
+1"#0 , %+1"#0 , % +1"160 or+1"160 or +1"#0 , &%+1"#0 , &% +1"#0+1"#0
-yphoid fe*er -yphoid fe*er&(r(typhoid fe*er&(r(typhoid fe*er
+1"#0 , %+1"#0 , % !1"160 or!1"160 or
+1"#0 , &%+1"#0 , &% !1"#0!1"#0
.(r)y infection or other.(r)y infection or other
s()mone))( infectionss()mone))( infections
!1"#0 , %!1"#0 , % +1"160 or+1"160 or
!1"#0 , &% +!1"#0 , &% + 1"#01"#0
/(ccin(tion or nonspecic/(ccin(tion or nonspecic
memory re(ctionmemory re(ction
C i
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Concusion
1 2 3 4 5 6 7
5 6666 66 66 6 " " "
7 6666 666 66 66 " " "
$8 66 6 " " " " "
$* " " " " " " "
194/ 19/ 191/ 1932/ 194/ 912/ %egative
control
3454Single test not diagnostic (-6ce't at !ig! titers 7 820)4Paired sam'les tests it! rising titer is diagnosticiagnostic4 " 7 1 90 7 1 1:0
agglutinins a''ear first
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&ro'one pheno!enon in
Agglutination tests
Pro;one effect < "ccasionally! it is observed that when
the concentration of antibody is high 1i#e# lowerdilutions2! there is no agglutination and then! as the
sample is diluted! agglutination occurs#Lack of agglutination in the pro)one is due to anti#ody
e6cess resulting in very small complexes that do notclump to form visible agglutination
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$i!itation of Widal Test
• The Widal test is time consuming and often times
when diagnosis is reached it is too late to start an
antibiotic regimen#
• 6n spite of several limitation many hysicians
depend on Widal Test
r.+.-.Rao ' 31
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(nterpretation of Widal test
• Test results need to be interpreted
carefully in the light of 9
0# ast history of enteric fever!3# Typhoid vaccination!
4# general level of antibodies in the
healthy populations in endemic areasof the world#
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False &ositive Reactions with
W(DA$ Test
0# patients who have had previous vaccination or
infection with / typhi#
3# "ross%reaction with non – typhoidal /almonella#
4# in association with some autoimmune diseases#
5# 6nfection with malaria
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False %egative Reactions with W(DA$
Test0# -arly treatment!
3# *elapses of typhoid fever#
4# 7ccasionally the infecting strains are
poorly immunogenic#
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Typical )erological &rofile After Acute
(nfection
$ote that during *einfections! 6g: may be absent or present at a low level transiently
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• #lide 0idal test is more !o!ular as it gives ra!id results.
*ualitati+e test:
1 dro! of undiluted !atient2s serum sam!le for
the 3 antigens is !laed on the irled ard.
1 dro! of eah of 3 salmonella antigens are added se!arately
rotated gently for 1 min. A""earance of agglutination gi+es ,ualitati+e results.
(semi4uantitative test is re!eated $ith dilutions of serum5
/lide Widal test9
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• Semi<=uantitati%e test
<Gl! 5<Gl! 3<Gl! 0<Gl! >Gl! of patient;s serum each for 3 salmonella antigens are placed on thecircled card#
one drop of specific antigen is added to each series of serum#
Agglutination of each of these is noted#
Inter'retation
<Gl corresponds to 0 in 3< dilution#
5<Gl corresponds to 0 in 5< dilution#
3<Gl corresponds to 0 in < dilution#
0<Gl corresponds to 0 in 0?< dilution#
>Gl corresponds to 0 in 43< dilution#
/lide Widal test 1"ont#29
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&revention
And
Treat!ent
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&revention
Two !ain typhoid fever prevention strategies*
+, -accination
.
., Avoid ris/y food and drin/s
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Medication
Antibiotics
• 8ntibiotics, such as ampiciin, choramphenico, fuoro:uinoone
trimethoprim"sufametho;a#oe, 8mo;iciin and ciprofo;acin etc used to
treat typhoid fever.
• $rompt treatment of the disease with antibiotics reduces the case"
fataity rate to appro;imatey 1<.
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)tudy 0uestions*
• +rite s!ort note
Sym'toms & Pre%ention of ty'!oid fe%er
41
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Assig!ent
• Write shortly on Widal test
ل– – – – ا د ب ع ى د ه د م ح ا ى د ي ه م ك ن د س د م ة ي ن ه ا ر ا ن
42
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A3> ?".