Name : Lie Khie Chen

Birth : Jakarta

Graduates

MD : FKUI 1994

Internist : FKUI 2003

Consultant : FKUI 2006

Occupation

Internal Medicine Department

Tropical Medicine and Infectious Diseases Division

Interest

Sepsis

Antimicrobial Treatment

Antimicrobial Resistance

Fungal Infection

HIV and opportunistic infections

Curriculum Vitae

Update on Pathogenesis and

Management of Typhoid fever

Khie Chen

Division of Tropical Medicine and Infectious Diseases

Departement of Internal Medicine

Medical Faculty Univesity of Indonesia

Dr. Cipto Mangunkusumo General Hospital

Jakarta

Typhoid Fever

Typhoid fever is an acute systemic

infection caused by Salmonella enterica

serotype typhi or paratyphi which is also

known as Salmonella typhi

Epidemiologic Distribution of Typhoid Fever

Some example of commonly

Occuring Salmonella serotypes and groups

Group Serotype

A S. paratyphi A

B S. paratyphi B

S. stanley

S. saintpaul

S. agona

S. typhimurium

C S. paratyphi C

S. choleraesuis

S. virchow

S. thompson

D S. typhi

S. enteritidis

S. dublin

S. gallinarium

Pathogenesis

Contaminated food of drinks Gastric acid

Bowel lumen

Mucosal defence

Colonization Adhesion to mucose

Invation to Peyer Patch

Regional Lymphadenitis Thoracic duct

1st systemic bacteriemia

Pathogenesis

Infection of RE system

Liver, Spleen

2nd Bacteriemia

Gall bladder Lung, Myocard

Kidney, etc

Reinfection in bowel mucose Systemic manifestation

Hyperplasia Peyer Patch Inflammation, erosion

Feces

Bleeding, perforation

First : ATTACHMENT

Second : MUCOSAL INVASION

Jade 2008

Salmonella Pathogenesis

Attachment

Type 1 Fimbriae fim

Long Polar Fimbriae lpf

Plasmid-Encoded Fimbriae pef

Thin Aggregative Fimbriae

agf

fim, lpf, pef genes

Type 1 fimbriae specifically bind -D-mannose

receptors on various eucaryotic cell types

LP fimbriae mediate adhesion to the cells of the

Peyer's patches of the small intestine in a

mouse model of infection

S. typhimurium, S. enteritidis, S. choleraesuis,

and S. paratyphi C, contain pef sequences . PE

fimbriae can adhere to histological sections of

murine small intestine more effectively

Jade 2008

Agf gene

Thin aggregative fimbriae (3 to

4 nm wide) (curli) were identified

and purified from S. enteritidis

• Curli-producing bacteria tend to autoaggregate,

a phenomenon which has been suggested to

enhance the survival of salmonellae facing

hostile barriers such as stomach acid or other

biocides they may encounter

Mucosal Invation

The mechanisms of Salmonella invasion, that is, the stimulation of nonphagocytic cells to internalize bacteria, are clearly complex.

Salmonella pathogenicity island 1 (SPI1), is believed to have been acquired by horizontal transfer from another pathogenic bacterial species during its evolution

Clinical Picture

• Fever

• Headache

• malaise

• myalgia

• nausea

• abdominal dis-

comfort

• constipation

• diarrhea

• dry cough

• epistaxis

• confusion, delirium

• psychosis

• convulsion

• coated tongue

• bradicardia relative

• tender abdomen

• hepatomegaly

• splenomegaly

• rose spots

• erythmatous muco

papular lesion

0 5 7 14

Fever pattern in Typhoid Fever

High fever

Headache

Abdominal discomfort

Diarrhea or constipation

Relative bradicardia

Leucopenia

Mild thrombocytopenia

Relative neutrofilia

Aneosinofilia

Fever pattern : typhoid fever

Typhus Inversus Pattern

Lowest early in the morning

Highest about 5.30 to 6.30 pm

Can be found in typhoid fever

tuberculosis

Pulse Temperature dissosiation

In normal temperature 37oC (99oF) pulse 80 beats/min

Increased 9 beats/min every 1oF

Relative bradicardia can be found in

enteric/typhoid fever

mycoplasma, malaria falciparum

Devervescence : 3-7 days after treatment

usually on 2nd or 3rd weeks

Female 31 yo, fever since 2 weeks ago

Hb 9.3 L 1600 Ht 28 Tr 107.000

Diff -/1/4/62/31/2 ESR 60 CRP 68

Widal ty O 1/160 H >1/640 ty B H 1/160

Treatment : Ceftriaxone 3g/day

Gall culture - PCR S typhi +

Clinical Presentation of Typhoid Fever

Headache 59 94.9

Epigastric pain 57 94.7

Nausea 108 90.7

Anorexia 41 90.2

Fever (>37.2) 118 89.8

Muscular pain 14 78.6

Rigor 37 78.4

Coated tongue 84 41.8

Vomiting 104 57.7

Cough 91 46.2

Relative bradicardia 117 34.2

Diarrhea 109 32.1

Constipation 109 33.9

Hepatomegaly 117 12.3

Splenomegaly 117 0.8

Clinical sign and symptom sum (n=119) %

Pohan HT, Indones J Int Med 2004;36(2)

Clinical scoring scale for typhoid

fever

Fever < 1 wk 1

Headache 1

Weakness 1

Nausea 1

Anorexia 1

Abdominal pain 1

Vomiting 1

Disturb GI motility 1

Insomnia 1

Hepatomegaly 1

Spelenomegaly 1

Fever > 1 wk 2

Relative bradicardia 2

Typhoid tongue 2

Melena stools 2

Impaired consciousness 2

Clinical typhoid fever if score > 13 of maximal 20

Adapted from : Nelwan RHH. Conns Current Traatment 2003

Laboratory Examination

Peripheral blood count leucopenia, leucocytosis

normal WBC count

mild anemia

thrombocytopenia

increased ESR

Serum transaminase increased ALT and AST

Albumin hypoalbuminemia

Serology Increased titer of

aglutinin O, H and Vi

Blood culture Salmonela typhi

PCR positive

Seroprevalensi Uji Widal pada

Komunitas Perkotaan di DKI Jakarta

Distribusi Seroprevalensi Uji Widal

55.7

6

71

6

78

64.3

78

23.6

0

10

20

30

40

50

60

70

80

90

S. typhi S. pth A S. pth B S. pth C

persentaseWidal O

Widal H

Djoko Widodo, Khie Chen, Suhendro, Ekowati Rahajeng 2006

Seroprevalensi Uji Widal pada

Komunitas Perkotaan di DKI Jakarta

Distribusi Titer Widal S. Thypi O dan H (n : 300)

8.7

26

6

10 0 0.3

11.7

17

15

5.7

1 1

13.7 14.3

12.3

0

5

10

15

20

25

30

20 40 80 160 320 640 1280 >1280

pe

rse

nta

se

Widal S. Thypi O

Widal S. Thypi H

Djoko Widodo, Khie Chen, Suhendro, Ekowati Rahajeng 2006

Seroprevalensi Uji Widal pada

Komunitas Perkotaan di DKI Jakarta

Distribusi Titer Widal S. parathypi A

5

10 0 0 0 0 0

21

4

17

7.7

9.3

4.3

0.7 0.3

0

5

10

15

20

25

20 40 80 160 320 640 1280 >1280

pe

rse

nta

se

Widal S. parathypi A O

Widal S. parathypi A H

Djoko Widodo, Khie Chen, Suhendro, Ekowati Rahajeng 2006

Seroprevalensi Uji Widal pada

Komunitas Perkotaan di DKI Jakarta

20

22.3

18.3

9

1.3

0 0 0

20.7

13

21.3

10 10.3

2

0.70

0

5

10

15

20

25

20 40 80 160 320 640 1280 >1280

Widal S. parathypi B O

Widal S. parathypi B H

Distribusi Titer Widal S. parathypi B

Djoko Widodo, Khie Chen, Suhendro, Ekowati Rahajeng 2006

Seroprevalensi Uji Widal pada

Komunitas Perkotaan di DKI Jakarta

20 40 80 160 320 640 1280 >1280

3.3

7.7

1

4.7

1

6

0.7

2.3

0

5

0

0.3

0

0.3

0 00

1

2

3

4

5

6

7

8

pers

en

tase

Distribusi sebaran serologi Widal S. parathypi C (n : 300)

Widal S. parathypi C O

Widal S. parathypi C H

Djoko Widodo, Khie Chen, Suhendro, Ekowati Rahajeng 2006

Blood culture and PCR results in diagnosis of

Typhoid Fever

Treatment Non Pharmacologic : Bed rest, Nutrition

Pharmacologic

Symptomatic

Antibiotic :

Ampicillin/Amoxicillin 2x750 or 3x500 mg

Chloramphenicol 4x500mg

Cephalosporin : Ceftriaxone 3-4 g/days

Fluoroquinolones : Ciprofloxaxin 2x500 mg

Ofloxacin 2x400 mg

Pefloxacin 1x400 mg

Fleroxacin 1x500 mg

Levofloxacin 1x500mg

South East Asia J Trop Med Pub Health

2006; 37 (1):126

Complications

Intestinal complication

intestinal perforation

gastrointestinal hemorrhage

hepatiitis, pancreatitis, paralytic ileus

Extraintestinal

Cardiovascular : shock, myocarditis

Neuropsychiatric : encephalopaty, delirium

psychosis

Respiratory : bronchitis, pneumonia, pleuritis

Hematology : anemia, DIC

Kidney : glemerulonephritis, pyelonephritis

Others : osteomyelitis, focal abscess

Carrier State

• Exist of S. typhi in feces or urine without

clinical manifestation 1 year after recovery from

typhoid fever

• S. typhi still be found in feces of urine

2 or 3 months after recovery in 16%

patients

• Impairment of host defence mechanism,

gall and kidney stone, chronic gall and

kidney infection contribute in

pathogenesis of carrier state

Carrier State

• Diagnosis of carrier state :

feces and urine culture, Vi antibody

• Treatment :

Without gall stone :

Ampicillin, Amoxicillin, Cotrimoxazole

With gall stone :

Cholecystectomi and treatment with

Ciprofloxacin or Norfloxacin

With Schistosomiasis :

Eradication of schistosomiasis before treatment

of carier state

Prevention

• Avoid risky food or drinks

• Hand washing

• Vaccination

• Detection of carrier state in food handler