TYPHOID

R.MADHURIROLL NO:O5PHARM-D II YEAR

INTRODUCTION

ETIOLOGY

TRANSMISSION

PATHOGENESIS

DIAGNOSIS

TREATMENT

PREVENTION

Typhoid or enteric fever is a clinical syndrome characterized by constitutional and gastro intestinal symptoms ,head ache. Typhoid fever is a bacterial infection of the intestinal tract and occasionally the bloodstream.

Typhoid is caused by Salmonella enterica serovar typhi (Salmonella typhi)

These waterborne gram negative aerobes are transmitted by consumption of contaminated food or drink.

INTRODUCTION

Salmonella enterica (formerly Salmonella choleraesuis) is a rod-shaped  flagellated facultative anaerobic ,gram negative bacterium.

Kingdom : eubacteriaFamily : EnterobacteriacieaGenus : SalmonellaSpecies : S. EntericaSalmonella enterica has 6 subspecies and each subspecies that differ by antigenic specificity.Secreted proteins are of major importance for the pathogenesis of infectious diseases caused by Salmonella

enterica.

ETIOLOGY

Antigens: located in the

cell capsule

• H (flagellar antigen).

• O (Somatic or cell wall

antigen).

• Vi (polysaccharide

virulence )Endotoxin

Resistance:

• Lives for 2-3 weeks in

water.

• 1-2 months in stool.

• Dies out quickly in

summer

Resistance to drying

and cooling

S.enterica serotype typhiMember of family Enterobacteriaciea

Ingestion of the bacteria via contaminated food or water.

About 3%-5% of patients become carriers of the bacteria after the acute illness.

These chronic carriers may have no symptoms.

Flies

TRANSMISSION

Salmonella Typhi

survives the acidity of the stomach

invades the Peyer’s Patches of the intestinal wall

macrophages (Peyer’s Patches)

the bacteria is within the macrophages and survives

bacteria spreads via the lymphatics while inside the macrophages

access to Reticuloendothelial system, liver, spleen, gallbladder and bone marrow

First week: elevation of the body temperatureSecond week: abdominal pain, spleen

enlargement and rosespotsThird week: necrosis of the Peyer’s Patchesleads to perforation, bleeding and, if left

untreated, death……

PATHOGENESIS

Poor appetiteMalaiseCoughSore throatHeadachesGeneralized aches and painsFever ascends in step wise fashion after 7 to 10 days

reaches plateau. Sustained fever as high as 103 F-104 F (39 C-40 C)LethargyDiarrhea.Chest congestion develops in many patients, abdominal

pain, distention and discomfort are common. About 10% of patients have recurrent symptoms

(relapse) after feeling better for one to two weeks. SpleenomegalyRelative bradycardiaRash(rose spots) appear during 2nd weak of disease. The

individual spot, found on the trunk, is a pink papule 2-3mm in diameter that fades on pressure. It disappears in 2-3 days

SIGNS & SYMPTOMS

Stage One:A slowly rising

temperatureRelative

bradycardia malaise (discomfort or uneasiness), headache and cough.

In ¼ of cases, epistaxis (acute hemorrhage from the nostril) can occur.

four stages, each lasting about a week.

Stage Two:Continuing high feverExtremely distended

abdomenConsiderable weight

lossBradycardia

continuesDelirium is frequent,

frequently calm and sometimes agitated.

Stage Three:A number of complications can occur:

Intestinal hemorrhage due to bleedingIntestinal perforationEncephalitis (inflammation of the

brain)Fever is still very highDehydration occurs and increases

deliriumLies motionless with eyes half-opened

Stage Four:Defervescence

(very high fever) commences that continues into the fourth week.

Laboratory findingsWBC count is decreased

Leukocytopenia(specially

eosinophilic leukocytopenia).

Bacteremia occurs earlyin the disease Blood Cultures arepositive in•1st week in 90%•2nd week in 75%•3rd week in 60%•4th week and later in 25%

Blood culture:

Identification of Salmonella•Sub cultures are done after overnight incubation at 37 centigrade ,and subcultures are done on MacConkey's agar Subcultures are repeated upto 10 days after further incubation.

DIAGNOSI

S

The bone marrow

culture

• You may have this test

if you have an

unexplained fever

• Bone marrow culture is

an examination of the

soft, fatty tissue found

inside certain bones.

This tissue, called bone

marrow, produces

blood cells.

• Doctor removes a small

sample of fluid bone

marrow through a

needle.

•Urine and stool cultures

• A stool sample is collected in a clean container and placed under conditions that allow bacteria or other organisms to grow. • The type of infection is identified by noting the appearance of the growth, by performing chemical tests on the stool sample, and by looking at the sample under a microscope.

The duodenal string test

Involves swallowing a string to obtain a

sample from the upper part of the small

intestine

You swallow a string with a weighted gelatin

capsule on the end. Four hours later it is

pulled back out.

Any bile, blood, or mucus attached to the

string is examined under the microscope for

cells and parasites .

Culture bile is useful for the diagnosis of

carriers.

Rose spots:

Not used routinely

WIDAL TEST INTRODUCTION: Enteric fever specific agglutinins (antibodies) are detected in patients after 15 days of fever. BCG vaccinated patient’s serum may show elevated titre of all three ‘H’ agglutinins. Stained salmonella antigens are used to detect and identify specific antibodies in serum samples from patients suffering from enteric fever.

PRINCIPLE: Bacterial suspension which carry antigen will agglutinate on exposure to antibodies to salmonella organisms.

SAMPLE : Fresh seurm is preferred. In case of any delay performing the test, serum should be stored at 20 - 80 C. REAGENTS: 1. Antigen suspension, S. typhi O. 2. Antigen suspension, S. typhi H. 3. Antigen suspension, S. paratyphi ‘AH’. 4. Antigen suspension, S. paratyphi ‘BH’. 5. Polyspecific positive cotrol 6. Glass Slides with 6 reaction circles and Mixing sticks.

observe for agglutination macroscopically within one minute.

PROCEDURE: SLIDE TEST

SEMI QUANTITATIVE METHOD :

•Pipette one drop of isotonic saline into the first reaction circle and then place 5, 10, 20, 40, 80 ul of the test sample on the remaining circles. • Add to each reaction circle, a drop of the antigen which showed agglutination with the test sample in the screening method.

STANDARD TUBE TEST METHOD 1. Take 3sets of 5 test tubes and label them 1 to 5 for O, H, AH and BH antibody detection. 2. Pipette into the tube No.1 of all sets 1.9 ml of isotonic saline.

3. To each of the remaining tubes (2 to 5) add 1.0 ml of isotonic saline. 4. To the tube No.1 tube in each row add 0.1 ml of the serum sample to be tested and mix well.

•Transfer 1.0 ml of the diluted serum from tube no.1 to tube no.2 and mix well.

•Transfer 1.0 ml of the diluted sample from tube no.2 to tube no.3 and mix well. Continue this serial dilution till tube no.4 in each set.

•Discard 1.0 ml of the diluted serum from tube No.4 of each set.

•Tube No.5 in all the sets, serves as a saline control. Now the dilution of the serum sample achieved in each set is as follows:

Tube No. : 1 2 3 4 5 (control) Dilutions 1:20 1:40 1:80 1:160 1:320 •To all the tubes (1 to 5) of each set add one drop of the respective WIDALTEST antigen suspension (O, H, AH and BH) from the reagent vials and mix well

•Incubate at 370 C overnight(18 hours)

INTERPRETATION OF RESULTS:

SLIDE TEST METHOD •Agglutination is a positive test result and if the positive reaction is observed with 20 ul of test sample, it indicates presence of clinically significant levels of the corresponding antibody in the patient serum. •No agglutination is a negative test result and indicates absence of clinically significant levels of the corresponding antibody in the patient serum.

QUANTITATIVE METHOD •The titre of the patient serum using Widal test antigen suspensions is the highest dilution of the serum sample that gives a visible agglutination. •The sample which shows the titre of 1:80 or more should be considered as clinically significant.

Etiologic and special treatment1.Quinolones:

it’s highly against S.typhi penetrate well into

macrophages,and achieve high concentrations

in the bowel and bile lumens

•Norfloxacin (0.1～ 0.2mg tid～ qid/10～ 14

days).

•Ofloxacin (0.2 mg tid 10～ 14days).

•ciprofloxacin (0.25 mg tid) caution: not in

children and pregnant

2.Chloramphenicol:

For cases without multiresistant S.typhi.

Children in dose of 50～ 60mg/kg/per day.

adult 1.5～ 2g/day. tid.

Unable to take oral medication, the same dosage

given intravenously

3.Cephalosporines: Cefoperazone and Ceftazidime. 2～ 4g/day .10~14 days.

Chronic carrier: •Ofloxacin 0.2 bid or ciprofloxacin 0.5 bid, 4～ 6 weeks.•Ampicillin 3～ 6g/day tid plus probenecid 1～1.5g/day. 4～ 6 weeks.•Cholecystitis may require cholecystectomy.Adequate waste disposal and protection of

food and water supplies from contamination are important public health measures to prevent typhoid fever.

Carriers can’t work as food handlers.

Immunization is not always effective but should be considered for household contacts of a typhoid carrier, for travellers to endemic areas and during epidemic outbreaks.

A multiple dose oral live-attenuated Ty21a vaccine is supplied as enteric coated capsules.

The capsules must be refrigerated and taken with cool liquids atleast 1 hour before meals. Boosters for every 5 years.

This vaccine is not recommended for infants,children less than 6 years and immunosuppressed patients.

A single dose Vi capsular polysaccharide(Vi CPS) vaccine is available for parenteral use. Boosters for every 2 years.

This vaccine is not recommended for infants younger than 2 years.

Both the vaccines are of equal efficacy but oral vaccine causes fewer side effects.

PREVENTION

REFERENCES• MICROBIOLOGY by MICHAEL J.PELCZAR,JR. ,E.C.S.CHAN, NOEL R.KRIEG

5th ed

• APPLIED MICROBIOLOGY by VINITHA KALE , KISHORE BHUSARI 2nd ed

•MICROBIOLOGY by PRESCOTT, HARLEY 7th ed• Cruickshank, R(1962) Medical Microbiology, 12th Ed, P:4003.

•www.medscape.com•www.giantmicrobes.com•www.kindnessofstrangerstravel.com•www.sabin.org•www.immunize.org

THANK YOU…………