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Lec6 Typhoid Fever

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Page 1: Lec6 Typhoid Fever

7/26/2019 Lec6 Typhoid Fever

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Page 2: Lec6 Typhoid Fever

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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: [email protected]

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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> ?".