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: 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 Salmonellafor

    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)

    antigensVi (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 !olysaharideex!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. Absencein 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

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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?

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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 whenthe 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