DIAGNOSIS OF TYPHOID FEVER updated

8/12/2019 DIAGNOSIS OF TYPHOID FEVER updated

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DIAGNOSIS OF TYPHOID FEVER

updatedDr.T.V.Rao MD

Dr.T.V.Rao MD 1


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Typhoid fevercommon problem in developing

Countries


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Manifest with

Rose spotsHigh fever

Diarrhea

Typhoid Meningitis

Aches and pains

Chest congestion
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Clinical manifestation Head ache, malise,anorexia ,coated tongue Abdominal discomfort, Constipation / Diarrhea Step ladder type fever, Relative bradycardia, A soft palpable spleen Hepatomegaly Rose spots appear

Dr.T.V.Rao MD 4


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Over view of Diagnosis of TyphoidFever

Infection with typhoid orparatyphoid fever results ina very low-gradesepticaemia. A single bloodculture is positive in onlyhalf of cases. Stool culture isnot usually positive duringthe early phase of the

disease. Bone marrowculture increases thediagnostic yield to about80% of cases.

Dr.T.V.Rao MD 5


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Bacteriological Diagnosis of Typhoid Fever

Selective media, such as Deoxycholate-citrate agar or xylose-lysine Deoxycholate

agar, are used for the isolation ofsalmonella bacteria from faeces. Fluidenrichment media, such as Tetrathionate

or selenite broth, are also useful todetect small numbers of salmonellae infaeces, foods or environmental samples.

Dr.T.V.Rao MD 6


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Bacteriological Diagnosis ofTyphoid Fever

Suspicious colonies from the cultureplates are tested directly for the

presence of Salmonella somatic (O)antigens by slide agglutination andsubcultured to peptone water for the

determination of flagellar (H) antigenstructure and further biochemicalanalysis.

Dr.T.V.Rao MD 7


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Bacteriological Diagnosis ofTyphoid Fever

A presumptive diagnosis of salmonellosiscan often be made within 24 h of the

receipt of a specimen, althoughconfirmation may take another day, andformal identification of the serotype

takes several more days. A negativereport must await the result ofenrichment cultures - at least 48 h.

Dr.T.V.Rao MD 8


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How we Diagnose Typhoid Fever Diagnosis is made by any blood, bone marrow

or stool cultures and with the Widal test(demonstration of salmonella antibodiesagainst antigens O-somatic and H-flagellar ). Inepidemics and less wealthy countries, afterexcluding malaria, dysentery or pneumonia, atherapeutic trial time with chloramphenicol is

generally undertaken while awaiting theresults of Widal test and cultures of the bloodand stool.

Dr.T.V.Rao MD 9


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Laboratory Diagnosis ofTyphoid Fever

1 Isolation of Bacilli. A Gold standard 2 Diagnosis for presence of Antibodies,

Positive Blood culture A gold standard Isolation from Feces and Urine ? Detection of Antibodies Inconclusive. Newer methods

Detection of antigen in Blood and Urine

Dr.T.V.Rao MD 10


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Blood Culture

1 st week Positive in 90 %2 nd week Positive in 75 %3 rd week Positive in 60 %> 3 weeks positive in 25 %Draw 5 10 cc of Blood by venipuncture.ADD to 50 -100 ml of Bile broth.Incubate at 37 c /Subculture in MacConkeyAt regular intervals

Dr.T.V.Rao MD 11


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Blood Cultures in Typhoid Fevers

Bacteremia occurs earlyin the disease

Blood Cultures are

positive in

1st week in 90%2nd week in 75%3rd week in 60%4 th week and later in 25%

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Castanedas method of Blood Culture

Double medium used Solid/Liquid medium inthe same Bottle.

Bottle contains Bile broth/agar slant, For subculture the bottle is merely tilted. A subculture into MacConkey at regular

intervals, Reduces the chances of contamination Increases the chances of isolation.

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Salmonella on Mac Conkey's agar

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Salmonella on XLD agar

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Clot culture Clot cultures are more

productive in yieldingbetter results in

isolation. A blood after clotting,

the clot is lysed withStreptokinase ,but

expensive to performin developingcountries.

Dr.T.V.Rao MD 16


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Bactec and Radiometric based methodsare in recent use

Bactek methods inisolation of Salmonella

is a rapid and sensitivemethod in earlydiagnosis of Entericfever.

Many MicrobiologyDiagnostic Laboratoriesare upgrading to Bactekmethods

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Biochemical Characters

Non Lactose fermenter, Motile Indole MR + VP - Citrate + Ferment Glu/Mal/Man Do not ferment Lactose/Sucrose

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Slide agglutination tests In slide agglutination

tests a known serumand unknown culture

isolate is mixed,clumping occurs withinfew minutes

Commercial sera areavailable for detectionof A, B,C1,C2,D, and E.

Dr.T.V.Rao MD 19


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Culturing other Specimens

Feces Enrichment in Tetrathionate brothand Selenite broth

Culturing in MacConkey/DCA/WilsonBlair medium Large black colonies. Urine Culture positive in 25 % Other samples

Bone Marrow,Bile,CSF/Sputum

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Why we still use Widal test The Widal test is an

old serologic assayfor detecting IgM

and IgG to the O andH antigens ofsalmonella. The testis unreliable but iswidely used in mostdeveloping countriesbecause of its lowcost. Dr.T.V.Rao MD 21


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Serology WIDAL Test Tube agglutination test. Detects O and H antibodies

Diagnosis of Typhoid and Paratyphoid Testing for H agglutinins in Dryers tubes, a

narrow tube floccules at the bottom

Testing for O agglutinins in Felix tubes, Chalky Incubated at 37 c overnight

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Widal Test In 1896 Widal A professor of

pathology and internalmedicine at the University ofParis (1911 29), he developed a

procedure for diagnosingtyphoid fever based on the factthat antibodies in the bloodof an infected individual cause

the bacteria to bind togetherinto clumps (the Widalreaction).

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Widal test S.typhi O and H tubes Paratyphi A/B H agglutinins only Common antigens O in all Factor sharing

12 Significance I st week negative. Titers raise in 2nd week Raise of titers

diagnostic Dr.T.V.Rao MD 24


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Diagnosis of Enteric FeverWidal test

Serum agglutinins raise abruptly during the 2 nd or 3 rd week

The Widal test detects antibodies against O and Hantigens

Two serum specimens obtained at intervals of 7 10days to read the raise of antibodies.

Serial dilutions on unknown sera are tested againstthe antigens for respective Salmonella

False positives and False negative limits the utility ofthe test The interpretative criteria when single serum

specimens are tested vary

Cross reactions limits the specificity


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Widal Test Single test not diagnostic. Paired samples tests Diagnostic.

O > 1 in 80H > 1in 160

H agglutinins appear firstFalse positives in Unapparent infection,

ImmunizationPreviously infected

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Widal test Anamnestic response previous

infection and responding tounrelated infection

Other Diagnostic testsCIE and ELISA

Detection of Circulating antigensCo agglutination test.

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Limitation of Widal Test The Widal test is

time consumingand often timeswhen diagnosis isreached it is toolate to start anantibiotic regimen.

In spite of severallimitation manyPhysicians dependon Widal Test

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False Positive and Negative Reactionswith WIDAL Test

The Widal test should be interpreted inthe light of baseline titers in a healthylocal population. This is especiallyimportant when there is a high localprevalence of non-typhoid salmonellosis.The Widal test may be falsely positive inpatients who have had previousvaccination or infection with S typhi.

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False Positive and Negative Reactionswith WIDAL Test

Widal titers have also been reported inassociation with the dysgammaglobulinaemiaof chronic active hepatitis and otherautoimmune diseases.64 '8 '9 False negativeresults may be associated with earlytreatment, with "hidden organisms" in bone

and joints, and with relapses of typhoid fever.Occasionally the infecting strains are poorlyimmunogenic.

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Diagnosis of Carriers andEnvironments

Fecal carriers byisolation fromspecimens. or Bileaspirated.

Sewer swabs Bacteriophage

typing

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Culturing and Identifying remain theGold standard

Newer serologic assaysfor S. enterica serotypeTyphi infection areoccasionally used in

outbreak situations andare somewhat moresensitive and specific thanthe Widal test, but arenot an adequatesubstitute for blood,stool, or bone marrowculture.

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Is there a definitive test to diagnoseTyphoid fever

Because there is nodefinitive serologic testfor typhoid orparatyphoid fever, theinitial diagnosis often hasto be made clinically. Thecombination of a historyof risk for infection and agradual onset of feverthat increases in severityover several days shouldraise suspicion of typhoidor paratyphoid fever.

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Newer methods in diagnosis ofTyphoid Fever

The serum samplescan be tested byusing newer

methodsMulti-Test Dip-S-Ticks, TyphiDot, andTUBEX to detectimmunoglobulin G(IgG), IgG and IgM,and IgM,respectively.Dr.T.V.Rao MD 34


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Immunoassays in Typhoid Fever

The immunoassay isalso used for thediagnosis. The

immunoassay are basedon the detection of theO and Vi antigens of S.typhi in blood or urine

using conglutination,ELISA, or countercurrentimmunoelectrophoresis. Dr.T.V.Rao MD 35


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Experimental and Molecular Methods

Polymerase chainreaction and DNAprobe methodattempt to employS.typhi genes andhybridize them with

labelled specificgene probes werealso used.

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Key points Antibiotics have no place in the

management of salmonella

gastroenteritis unless invasivecomplications are suspected.

Clean water, sanitation and hygienichandling of foodstuffs are the keys toprevention.

Dr.T.V.Rao MD 37


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Coalition against Typhoid Since May 2011, the

Coalition against Typhoid(CaT) has featured monthlyarticles in the WHOs Global

Immunization Newsletters(GIN). The articles, writtenby CaT members fromaround the world, highlight

important work being doneto accelerate adoption oftyphoid vaccines.

Dr.T.V.Rao MD 38


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Programme Created by Dr.T.V.Rao MD

for Medical and Paramedical students inthe Developing world Email

[email protected]

D TVR MD 39

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DIAGNOSIS OF TYPHOID FEVER updated