4. Tropis 4 2012 (Salmonella)

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    Mochammad Hatta@2013Mochammad Hatta@2013

     SALMONELLA TYPHI 

      Prof. Dr. Mochammad Hatta, Ph.D, SpMK (K)

      Dept Microbiology, Fac.Medicine,

     Hasanuddin ni!ersity,

    Ma"asssar

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    Electron micrograph of a metal-shadowed whole cell ofSalmonella typhi, showing agella and shorter straightmbriae (magnied 7,800 times)

    Mochammad Hatta@2013Mochammad Hatta@2013

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    Mochammad Hatta@2013Mochammad Hatta@2013

    • Disease : Demam #ifoid (#yphoid Fe!er) 

    Gastrointestinal infection -- endemik in Indonesia--developing

      countries -- environmental/sanitation/hygiene relationship

      (Hattta M et al! "rans! #oyal "rop! Med! Hyg $ond %&&'

    • )amily : *ntero+acteriaceae -- Gram negative -- non-sporing  +acillus -- %-, -- motile -- long peritrichous flagella -- aero+e/

      facultative anaero+e -- temperature .o- ,.o 0 optimum '1o 2

    • 2olonies on Mac2onkey3s medium 0 44 agar

    • 5iochemical reactions: Glucose 0 mannitol: fermentation (6 0

    gas (6 -- lactose 0 sucrose : fermentation (- 

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    Mochammad Hatta@2013Mochammad Hatta@2013

    • $iability : death point : 7o 2

    • In soil survival for 7 8eeks

    • Pathogenesis : infection +y ingestion --- small intestinal via

      lymphatics --- mesenteric glands -- multiplication --- +lood via

      thoracic duct --- +acteriaemic phase ( . - .& days : infection

      liver gall +ladder spleen kidney 0 +one marro8!

      Gall +ladder --- invasion lymphoid tissue -- 9eyer3s patches

      0 lymphoid follicles -- acute inflammatory reactions --- ulcer

    haemorrhage -- perforation 0 necrosis

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    CLINICAL PICTURE

     Symptoms begin with sudden onset of high-

    grade feer! heada"he # dry "ough$

    %eer is swinging or may show step &adder

    pattern # patient initia&&y fee& we&& # mobi&e$

     Abdomina& pain # to'i"ity fo&&ow soon # by

    the end of (st wee) sp&een is pa&pab&e # pin)!

    dis"rete! s)in rash appears oer the trun)$

     Constipation is more "ommon than diarrhea

    whi"h is usua&&y greenish in "o&or *pea soup+$

    Mochammad Hatta@2013Mochammad Hatta@2013

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    CLINICAL PICTURE,

     Abdomina& tenderness # hepatomega&y o""ur

    in ./0 of patients$

     The pu&se is re&atie&y s&ow in re&ation to feer

    *Paget sign+$

     The tongue is "oated with free margins #ha&itosis may be present$

    The sweat of some patients sme&& &i)e yeast$

    Mochammad Hatta@2013Mochammad Hatta@2013

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    CLINICAL PICTURE,1

     The 1rd wee) of i&&ness is the usua& time for

    "omp&i"ations in the untreated patients$

     Lo"a& gut as we&& as systemi""omp&i"ations may o""ur$

     Serious infe"tions may progress rapid&y to

    drowsiness # "oma whi"h is usua&&y fata&*"oma igi&+$

     2orta&ity is un&i)e&y after the 3th wee) #

    patients may be"ome "arrier if not treated$Mochammad Hatta@2013Mochammad Hatta@2013

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    Enteric fe!er" #ose spotsEnteric fe!er" #ose spots

    Paratyphoid feverTyphoid fever

    Mochammad Hatta@2013Mochammad Hatta@2013

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     Intestina& hemorrhage

     Para&yti" i&eus

     Intestina& perforation

    L4CAL C42PLICATI4NS

     5en)er degeneration of abdomina& mus"&es

    Mochammad Hatta@2013Mochammad Hatta@2013

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     Endo"arditis

     Arteritis # arteria& embo&i

     Cho&e"ystitis

    S6STE2IC C42PLICATI4NS

     4steomye&itis # septi" arthritis

     7epati" # sp&eni" abs"esses

     Pneumonia or empyema

     2eningitis

     Urinary tra"t infe"tionMochammad Hatta@2013Mochammad Hatta@2013

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    Mochammad Hatta@2013Mochammad Hatta@2013

    P4SITI8E CULTURE AN9 Ig2 ANTI:496 RESP4NS IN T6P74I9P4SITI8E CULTURE AN9 Ig2 ANTI:496 RESP4NS IN T6P74I9

    %E8ER%E8ER 

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     $yphoid fe!er $yphoid fe!er%aboratory diagnosis%aboratory diagnosis

    • Polymerase Chain Reaction (PCR)Polymerase Chain Reaction (PCR)

    • Culture of blood or bone marroCulture of blood or bone marro& !0" durin# first ee$!0" durin# first ee$

    • Culture of urine or stoolCulture of urine or stool& in %resence of characteristic clinical %icturein %resence of characteristic clinical %icture

    • &erolo#y test&erolo#y test& antibody test a#ainst somatic (') orantibody test a#ainst somatic (') or

    fla#ellar (H) anti#enfla#ellar (H) anti#en

    Mochammad Hatta@2013Mochammad Hatta@2013

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    Mochammad Hatta@2013Mochammad Hatta@2013

    Prinsip tehni" Polymerase %hain &eaction (P%&)

      D:; yang akan  ' *

      diamplifikasi  * +++++++++++++++++++++++++ '

      Denaturasi 6 primer 

     

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    Mochammad Hatta@2013Mochammad Hatta@2013

    Deteksi Salmonella typhi dengan :ested 92# 

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    Mochammad Hatta@2013Mochammad Hatta@2013

    Typhoid feer Typhoid feer 

    *nested+*nested+

    ST( ; .

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    Mochammad Hatta@2013Mochammad Hatta@2013

     

    Hasil nested 92# S.typhi dari penderitademam tifoid

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    Mochammad Hatta@2013Mochammad Hatta@2013

    MD& P%& product  S.typhi  $ietnam and /ndonesian isolated

      >ietnam Indonesia

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    Mochammad Hatta@2013Mochammad Hatta@2013

    MD# 92# product 4!typhi >ietnam isolated

    012 bp

    320

    4*0

    *25

     

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    Mochammad Hatta@2013Mochammad Hatta@2013

    P%& for the detection of S. typhi  specific D67 in blood, stool and urine

    samples from patients 8ith suspected typhoid fe!er.

      6o (9) of patients 8ith the follo8ing result

      Patient group :lood Faeces rine  6eg Pos 6eg Pos 6eg Pos

      2ulture positive . (. 1. (?? .7 (71 @ ('' %% ('@ '7 (7%

      2ulture negative %. (,/ %7 (// 1 (,. .& (/? .. (%@ %@ (1%

      :on-typhoid patients .% (.&& & (& % (.&& & (& .& (.&& & (&

    (/6%;D% 55>)

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    Mochammad Hatta@2013Mochammad Hatta@2013

    CONSTRAINTS OF PCRCONSTRAINTS OF PCRTECHNIQUETECHNIQUE

    11 uite e*%ensi+euite e*%ensi+e

    2 ,eed s%ecial e-ui%ment2 ,eed s%ecial e-ui%ment

    3 ,eed hi#h s$ill and laboratory3 ,eed hi#h s$ill and laboratory

    . &o%histicated. &o%histicated

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    Mochammad Hatta@2013Mochammad Hatta@2013

    SalmonellaSalmonella

    bateria onbateria on

    !aCon"ey!aCon"ey

    a#ara#ar

    $ato%e&$ato%e&

    po%itivepo%itive

    bateria %ho'bateria %ho'

    pin" olonie%pin" olonie%()pper left*()pper left*

    $ato%e&$ato%e&

    ne#ativene#ative

    bateria havebateria haveolorle%%olorle%%

    olonie% (lo'erolonie% (lo'er

    ri#ht*ri#ht*

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    Mochammad Hatta@2013Mochammad Hatta@2013

    +iohemial reation% for identi,ation+iohemial reation% for identi,ation

    of of   S. typhiS. typhi by theby the API -.E proed)reAPI -.E proed)re

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    Mochammad Hatta@2013Mochammad Hatta@2013

    +la"+la"olonie% of olonie% of  Salmonell Salmonell 

    a typhia typhi

    afterafter#ro'th on#ro'th on

    bi%m)thbi%m)th

    %)l,te%)l,te

    a#ara#ar

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    Mochammad Hatta@2013Mochammad Hatta@2013

    'ipstic for $yphoid e!er'ipstic for $yphoid e!er

    *roced+re*roced+re& dd .l ser+m to /0.l detection reagentdd .l ser+m to /0.l detection reagent& nc+bate dipstic for 1 ho+rsnc+bate dipstic for 1 ho+rs

    & #inse with tap water#inse with tap water& #ead by !is+al inspection#ead by !is+al inspection

    #es+lt#es+lt

    (2ochammad 3atta, et al merican 4(2ochammad 3atta, et al merican 4 $ropical $ropical

     2edicine 5 3ygiene, /00/)2edicine 5 3ygiene, /00/)

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    Mochammad Hatta@2013Mochammad Hatta@2013

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    Mochammad Hatta@2013Mochammad Hatta@2013

    'ipstic for $yphoid e!er'ipstic for $yphoid e!er

    *roced+re*roced+re& dd .l ser+m to /0.l detection reagentdd .l ser+m to /0.l detection reagent& nc+bate dipstic for 1 ho+rsnc+bate dipstic for 1 ho+rs& #inse with tap water#inse with tap water

    & #ead by !is+al inspection#ead by !is+al inspection

    #es+lt#es+lt 9atients 8ithclinical

    suspicion of

    typhoid feverfrom Makassar

    Indonesia

    2ontrol

    "est

    $ h id 'i ti $yphoid e!er 'ipstic

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    Mochammad Hatta@2013Mochammad Hatta@2013

     $yphoid e!er 'ipstic $yphoid e!er 'ipstic6$', 3o 6hi 2inh 6ity, iet am6$', 3o 6hi 2inh 6ity, iet am

    6omparison of tests6omparison of tests 

     $est Sensiti!ity (9) Specicity (9)

    g2 E%S ≥:";00g< E%S ≥:":=00g E%S ≥:"/00

    7=8/

    >;>/>

    ?idal @ ≥:";00?idal 3 ≥:"/00 ;7=0 >1>8

    'ipstic 77 >

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    Mochammad Hatta@2013Mochammad Hatta@2013

     $yphoid e!er 'ipstic $yphoid e!er 'ipsticSemarang, ndonesiaSemarang, ndonesia

    Patient #ro)p/  )lt)re re%)lt

    N)mber po%itive (0 * 1 total

    2r3 4ariadi Ho%pital(bone marrow c+lt+re)  S. typhi po%itive  S. typhi ne#ative

    5 di%trit ho%pital%

    (blood c+lt+re)

      S. typhi po%itive  S. typhi ne#ative

    56 (7.38* 1 98. (.* 1 -

    5- (6:39* 1 57- (737* 1 -:

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    Mochammad Hatta@2013Mochammad Hatta@2013

     $yphoid e!er 'ipstic $yphoid e!er 'ipstic

    2aassar, ndonesia2aassar, ndonesia

    Patient #ro)p No3 po%itive (0 * 1total

    S)%pet%

      Clinial dia#no%i%; typhoid  S. typhi )lt)re po%itive  S. paratyphi )lt)re po%itive  C)lt)re ne#ative

      Clinial dia#no%i%; other  C)lt)re ne#ative

    Ho%pital ontrol%Shool hildren

    69 (8739* 1

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    Mochammad Hatta@2013Mochammad Hatta@2013

     $yphoid e!er 'ipstic $yphoid e!er 'ipstic

    2aassar, ndonesia2aassar, ndonesiaollow-+pollow-+p

    Sample 2PO No3 po%itive (0 * 1Total

    S. typhi )lt)re po%itive irst Second $hird

    S.typhi )lt)re ne#ative irst Second $hird

    6

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    Mochammad Hatta@2013Mochammad Hatta@2013

     $yphoid fe!er $yphoid fe!er

    6+lt+re and 'ipstic6+lt+re and 'ipstic

    A%%ay

    C)lt)re

    2ip%ti" 

    Sen%itivity

    :93=0

    87390

    Spei,ity

    780

    :90

    'ipstic" nger pric blood, same day res+lt

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    Mochammad Hatta@2013Mochammad Hatta@2013

    #apid test for typhoid fe!er#apid test for typhoid fe!er

    A 809 sensiti!ity compared with blood809 sensiti!ity compared with bloodc+lt+rec+lt+re

    A ** (>/9) and * (=;9) somewhat** (>/9) and * (=;9) somewhatlower than that of c+lt+relower than that of c+lt+re

    A Same day res+ltSame day res+lt

    A Easy to performEasy to performA 3igh stability of components3igh stability of components

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    Mochammad Hatta@2013Mochammad Hatta@2013

    2IPSTIC4 FOR 2ETECT I?!2IPSTIC4 FOR 2ETECT I?!

    ANTI+O2IESANTI+O2IES

    1 &im%le and ra%id1 &im%le and ra%id

    2 Re-uired no e-ui%ment2 Re-uired no e-ui%ment

    3 Hi#hly stable rea#ents3 Hi#hly stable rea#ents

    . /o cost. /o cost

    asy to a%%lied in field asy to a%%lied in field

    !ohammad Hatta, 2arga '

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     $B*3@' %ateral low $B*3@' %ateral low*rinciple*rinciple

    Immuno"hromatographi" strip assay

    2est Control

    &am%le %ad Con4u#ate 5etection stri% &in$blood cell %ad

    se%aration filter 

    Mochammad Hatta@2013Mochammad Hatta@2013

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     $B*3@' %ateral low $B*3@' %ateral low2ethod2ethod

    •  6dd  6dd µµl seruml serum

    •  6dd 130 6dd 130µµl sam%le fluidl sam%le fluid

    • 7ait 10 minutes7ait 10 minutes

    • Read resultRead result

    4ample 8ell

    2ontrol line

    "est line

    Mochammad Hatta@2013Mochammad Hatta@2013

    !ohammad Hatta, $heresia 3 bdoel, 3en% Smits Simple, rapid and aCordable point-of-care test for the serodiagnosis of typhoid fe!er

     J. Diagnostic Microbiology and InfectiousDisease ol =: (/) " :/>-:1;, eb (-..6*3

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    Mochammad Hatta@2013Mochammad Hatta@2013

    Typhoid %eer Late' Agg&utinationTyphoid %eer Late' Agg&utination

    seconds . seconds

    , seconds A 7& seconds

      $heresia 3 bdoel, #ob *astoor, 3en % Smits,!ohammad Hatta/ %aboratory e!al+ation of a simple andrapid lateD aggl+tination assay for the serodiagnosis oftyphoid fe!er. Transactions of the Royal Society ofTropical Medicine and Hygiene. !ol :0: (:0), :01/-:018(-..7*3

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    TREAT2ENT

     2edi"a& "are in"&ude rehydration! antipyreti"s #antibioti"s$

     9rugs of "hoi"e are Ceftria'one # "iprof&o'a"in

    but Cotrimo'a?o&e # Ch&orampheni"o& are sti&&used in dee&oping "ountries$ Ampi"i&&in )i&&s

    ba"i&&i hiding in the bi&e # hen"e preents or

    redu"e the "arrier state$

     Chroni" resistant "arrier state may ne"essitate

    "ho&e"yste"tomy$ Surgi"a& "are may a&so be

    needed in patients with intestina& "omp&i"ations$Mochammad Hatta@2013Mochammad Hatta@2013

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    NURSIN= CARE

     Iso&ation # barrier nursing is indi"ated

     Tra"e sour"e of infe"tion$

     "ontinue breastfeeding infants # young "hi&dren

    and gie 4RS # &ight diet for other patients in the

    first 3@ hours$

     Notifi"ation of the "ase to the infe"tion "ontro&

    nurse in the hospita&$

    Mochammad Hatta@2013Mochammad Hatta@2013

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    PRE8ENTI4N

     Edu"ation on hygiene pra"ti"es &i)e hand

    washing after toi&et use # aoidan"e of eating in

    non hygieni" restaurants$

    Antibioti" prophy&a'is is not needed for

    house-ho&d "onta"ts$

     Proper hand&ing # refrigeration of food een

    after "oo)ing$

     Sa&mone&&a TA: a""ine is aai&ab&e butaffe"tiity is &ow *./0 "&aimed prote"tion+$

    Mochammad Hatta@2013Mochammad Hatta@2013

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    PR4=N4SIS

     ith ear&y diagnosis and prompt treatmentmost patients with typhoid feer wi&& re"oer in

    due time$

     %eer # to'i"ity subsides within B hours ofantibioti" treatment$

    2orta&ity is ./0 in untreated seere typhoid

    feer parti"u&ar&y in "hi&dren # e&der&y$

     Re"rudes"en"e is rare but "hroni" "arrier

    state is reported in (/0 of patients$Mochammad Hatta@2013Mochammad Hatta@2013

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     Infe"tion fo&&ows ingestion of "ontaminated

    food or water$ 2eat! pou&try! eggs # diary

    produ"ts are freDuent sour"es$

    TRANS2ISSI4N

     Pets! domesti" anima&s and infe"ted human

    are potentia& reseroirs$ Person to person #

    anima& to human transmission is re"ogni?ed$

     In hea&thy humans a dose of about one mi&&ion

    ba"teria is ne"essary to produ"e symptoms$

    Mochammad Hatta@2013Mochammad Hatta@2013

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    #eferences#eferences

    A !ohammad!ohammad HattaHatta, 2iram Faer, Stella !an Feer, $heresia 3 bdoel, 3en % Smits #is, 2iram Faer, Stella !an Feer, $heresia 3 bdoel, 3en % Smits #isfactors for clnical typhoid fe!er in !illages in #+ral So+th S+lawesi, ndonesiafactors for clnical typhoid fe!er in !illages in #+ral So+th S+lawesi, ndonesia InternationalInternational Journal of Tropical Medicine Journal of Tropical Medicine ol ; (1)" >:->>, ol ; (1)" >:->>, (-..=*(-..=*

    A !ohammad!ohammad HattaHatta andand  #atnawati Enteric fe!er in endemic areas of ndonesia" an#atnawati Enteric fe!er in endemic areas of ndonesia" anincreasing problem of resistanceincreasing problem of resistance. J. Infection Developing ountries. J. Infection Developing ountries (( JID JID*3*3 ol /(;)G />8-ol /(;)G />8-

    10:10: (-..6*(-..6*

    A #ob *astoor,#ob *astoor, !ohammad!ohammad HattaHatta, $heresia 3 bdoel, 3en % Smits, $heresia 3 bdoel, 3en % Smits Simple, rapid andSimple, rapid andaCordable point-of-care test for the serodiagnosis of typhoid fe!eraCordable point-of-care test for the serodiagnosis of typhoid fe!er J. Diagnostic J. Diagnostic

    Microbiology and Infectious DiseaseMicrobiology and Infectious Disease ol =:"(/)G:/>-:1;, eb ol =:"(/)G:/>-:1;, eb (-..6*3(-..6*3A !ohammad!ohammad HattaHatta and 3en % Smits 'etection ofand 3en % Smits 'etection of Salmonella typhiSalmonella typhi by nested *olymeraseby nested *olymerase

    6hain #eaction in blood, +rine and stool samples6hain #eaction in blood, +rine and stool samples American J. Tropical Medicine American J. Tropical Medicine

    Hygiene.Hygiene.!ol " 7=G:1>-:;1!ol " 7=G:1>-:;1 (-..7*(-..7*

    A  $heresia 3 bdoel, #ob *astoor, 3en % Smits, $heresia 3 bdoel, #ob *astoor, 3en % Smits, !ohammad!ohammad HattaHatta// %aboratory e!al+ation%aboratory e!al+ationof a simple and rapid lateD aggl+tination assay for the serodiagnosis of typhoid fe!erof a simple and rapid lateD aggl+tination assay for the serodiagnosis of typhoid fe!er ..

    Transactions of the Royal Society of Tropical Medicine and HygieneTransactions of the Royal Society of Tropical Medicine and Hygiene !ol :0: (:0)G !ol :0: (:0)G

    :01/-:018:01/-:018 (-..7(-..7**

    A !ohammad!ohammad HattaHatta, 2arga '