Typhoid Fever

Division Tropical Medicine and Infectious Diseases

Department of Internal Medicine
Medical Faculty Veteran National Development University
Gatot Soebroto Central Army Hospital
Permission and Adapted from Umar Zein, Tropical
and Infectious Diseases Division Internal Medicine
Department AdamMalik Hospital Medan

BIO DATA
Nama
: Dr. Soroy Lardo, SpPD FINASIM
Pangkat/Nrp
: Letkol CKM/1920013110563
Kesatuan
: Departemen Penyakit Dalam RSPAD
Status
: K-3
Riwayat Penugasan :
Dokter Yonif 132/BS Kodam I/BB
Pasiwatkes Rumkit Putri Hijau Kodam I/BB
Ka Rumkitban Binjai Kodam I/BB
Ka Bangsal Paviliun Rumkit Putri Hijau Kodam I/BB
Kasidiklitbang Departemen Paru RSPAD Gatot Soebroto
Kabagyanmed Departemen Penyakit Dalam RSPAD Gatot
Soebroto
Kasub SMF Penyakit Tropik dan Infeksi DepartemenPenyakit
Dalam
Riwayat Pendidikan :
Fakultas Kedokteran UNPAD 1991

Term : Typhoid fever

Paratyphoid fever
Also known as : Enteric fever
It is an acute generalized infection of the
reticuloendothelial system, intestinal lymphoid tissue,
and gall bladder
Are severe systemic and life-threatening
illnesses
characterized by sustained fever and
abdominal
Symptoms

Gaster (stomach)

Enteric
(small intestine)

Colonic
(large intestine)

Etiology / Microbiology
Clinical Manifestations
Pathogenesis
Diagnosis
Treatment
Complications

SALMONELLOSIS
(Infections caused by Gram-negative bacteria)

Taxonomy :
SALMONELLAE sp. : 2000 serotypes
Human infection :
S. enterica subspesies enterica
which three serotypes :
1. S. typhi
2. S. typhimurium (S. paratyphi A and B),
now called : S. schottmulleri
3. S. choleraesuis
CHAMBERS. Infectious Diseases. In: Lawrence, et al. Current MD&T,
34th Edition. A Lange medicalbook Intl Ed. 1995;1173-9.

Clinical Patterns of
Infection
1.

2.

3.

Enteric fever (typhoid fever), due

to serotype typhi.
Acute enterocolitis, caused by
serotype typhimurium.
Septicemic type, due to serotype
choleraesuis, characterized by :
- bacteremia
- focal lesions

This is responsible for 75% of reported cases of food poisoning in UK

How in INDONESIA ?

Microbiology :
Most commonly caused by
Salmonella typhi
Salmonella paratyphi A, B, C
The other serotypes : S.choleraesuis
S.enteretidis
S.arizonae

Salmonellosis

: Enteric fever

Gastroenteritis
Sepsis

Family
Enterobacteriaceae
Motile
Somatic
Flagelar

antigen

Vi

Facultative anaerobic/aerobic
Gram (-) bacteria
Rods shape

Susceptibility to Disinfectants :
1. 1 % Sodioum hypochlorite
2. 2 % Glutaraldehyde
3. Iodine
4. Phenolics
5. Formaldehyde

Physical Inactivation :
1. Sensitive to moist heat (1210C) for at least 15 min
2. Dry heat (160 1700C) for at least 1 hour
Survival outside Host :
.Ashes 130 days
.Rabbit carcass 17 days
.Dust up to 30 days
.Feces up to 62 days
.Linoleum floor 10 hours
.Ice 240 days

Epidemiology :
Worldwide, except in industrialized regions such us the
United State, Canada, western Europe, Australia, and Japan
In the developing world, it affects about 12.5 million
persons each year
Over the past 10 years, travelers from the United States to
Asia, Africa, and Latin America have been especially at risk
Typhoid fever can be prevented and can usually be treated
with antibiotics
Multi-drug resistant strains have appeared in several areas
of word
Indonesia 760 810 cases / 100.000 / year with death rate
3.1-10.4 %

Infectious Dose : 100,000 organism ingestion

variable with gastric acidity
and size inoculum
Mode of Transmission :
1. Person-to-person
2. By contaminated food or water
3. By food contaminated by hand of carriers
4. Food contaminated by materials
5. Flies can infect food mechanical vector

Route of Transmission of Typhoid Fever

Patient

Indirect
Infection
> 90 %

Infected
Water
Food

Chronic carrier

Stool
Vomit
Urine

Healthy
subject

Typhoid
fever

Direct
Infection
< 10 %

Faktor Penentu
Virulensi
Salmonella thypi

Somatik (O) ada 2

determinan
Antigen (endotoksin
LPS, aceltylated
glucosamine
dissaccharide lipid A

Flagella protein (H)

antigen (fase 1 dan
II)

Capsular Vi (Polysaccharide
(Vi) ada 2 determinan
antigen (O)- acetyl N acetyl
carboxyl)

Outer Membran Proteins (OMPS)

Porin (Omp
B,C,D dan
OmpR)

Non
Porin

Patofisiologi
Makan
an yg
tercem
ar

Duktus
Torasiku
s

Masuk
PD ke
RES
(hati,
limpa,
SST)

Menemb
us
mukosa
usus

Kelenjar
limfe
usus
(replikas
i)

Ke
Pembul
uh
darah

BAKTEREM
IA 1
(24-72jam)
Kapsul
Vigagal
fagositosis
Replikasi pesat
(7-10hari)

BAKTEREM
IA2

Bakteremia
ke-2
Endotok
sin (LPS)

C3a,
C5a
IL
2

Sel Plasma
Limfosit B
& Agglutinin
O
Sel Plasma
&
Limfosit B
Limfosit
Agglutinin H &
T
Agglutinin Vi

T-helper

pirogen
IL1

Hipotalamu
s demam

agglutinin O terbentuk lebih dahulu daripada

agglutinin H dan agglutinin Vi. Aglutinin O cepat
menghilang dalam beberapa tahun. Sedangkan
agglutinin Vi menghilang setelah penderita
sembuh tetapi cenderung menetap pada karrier.

Imunopatogenesis
Terdapat 4 komponen antigenic penting pada S typhi:
1. Kapsular Vi
2. Lapisan luar (antigen O)
3. Flagella protein (antigen H)
4. Outer Membrane Protein (OMP)

S typhi
Resists the low pH of stomach

Membrane bound vacuoles

enterocytes, SpiC

Reach SMALL
INTESTINE

Salmonella next penetrate the

mucous layer of the gut
Bacterial proteins mediate in
the ACTIN, a-actinin,
trombomyosin, talin

Bac must survive the

antimiCrobial environment of
macrophage, which includes
the production of
antimicrobial peptides and
hydrolytic enzyme

Microfold cell (M cell)

Peyers patches, multiply
in mononuclear phagocyte
Spread to the phagocyte of
the liver, gallbladder & spleen
Cytokines, IL16, IL6, TNFalfa, TNF-R, p55

Clinical
manifestation

Bacteremia, endotoxin
release

Incubation Period : 1 3 weeks

depends on :
size of infecting dose
age
gastric acidity
immunologic status

Communicability :
As long as typhoid bacilli appear in excreta
Usually 1st week throughout convalescence
10 % of patients discharge bacilli for 3 months
after onset
2 5 % become chronic carriers may shed
bacteria for years

Clinical Manifestations (1):

Febril illness 5 to 21 days
Abdominal pain
chills
constitutional symptoms
in developed country : travelers or visitors from
endemic area

Clinical Manifestations (2):

Anorexia
Nausea
Vomiting
Diarrhea

Pea soup stool

Typhoid fever ( enteric fever )

Enteric
fever
syndrome
Headache
Anorexia
Rose spots
Splenomega
ly

Fever

Chills

Malaise
Weight loss
DIC
Bacteremia

Abdominal pain
weakness
Hepatomegaly
hypotension

Classic presentations :
First week of illness : stepwise fever &
bacteriemia
Second week : abdominal pain and rash
Third week : hepatosplenomegaly, intestinal
bleeding and perforation, secondary bacteriemia
and peritonitis

Clinical type of Vital Sign

(Stepwise fashion fever)
High
PATHOGENESIS :
Small intestine :
Plaque Peyeri Necrosis separation of slough Perforation
or healing ( ulceration, hemorrhages
Incubation
up to perforation ) or healed

periode

10-12 days
S. Typhi
Mouth
Peyers patch
Blood stream
V.Velea
Intestine
Peyers patch

Normal

Week1

Week2

Week3

Week4

Chronic
periode
Relaps or
Carrier

Tripple Cross
--- Blood pressure
--- Temperature
--- Pulse
Adapted from Syafruddin ARL RSPAD 2005

Pathogenesis :
Ingestion of S.typhi

MULTIPLI
CATION

Excreted in stool
and Urine

Inflammation, necrosis,
Ulceration Payers patches

Liver, GB, Spleen,BM

Multiply within MNPC

Enter the small intestine

Infection carried in the

Lymphoid follicle

Draining mesenteric
Lymph node

Entering thoracic ducts

Passed through the heart
End incubation period

Secondary bacteremia

Primary bacteremia

Pathology :
Payers patches :
Hyperplasia during the first week
Necrosis in second week
Ulceration during third week
Healing takes place without scarring
during forth week
The ulcer are oval shaped,
in the long axis of lower ileum
Separation of the sloughs hemorrhage and
perforation

Diagnosis :
1.Isolation of Organism :
- Blood cultures : positive in 40 80 % patients
during the first 7 10 days
- Culturing stool
- urine
- rose spots
- duodenal contents via string capsule : positive in
30 40 % patients
- bile
- faeces

2. Detection of antigen in body fluid :

- Coagglutination
- Latex agglutination
- ELISA
- CIEP
Urine test Typhidot

3. Detection of antibodies :
- Widal tube test
- Widal slide test
- IHA
- CIEP
- RIA
- ELISA

Laboratory Findings :
Anemia
Leucopenia or leucocytosis
Thrombocytopenia
Abnormal liver function

Diagnosis :

1. Clinical Signs and Symptoms

2. Laboratory findings
3. Isolation of the organism
4. Detection of microbial antigen
5. Titration of antibody against
causative agent

Skor Nelwan (Demam Tifoid)

Dari hasil pemeriksaan klinis pada saat penderita masuk RS diambil data-data
sesuai dengan yang diajukan oleh Nelwan (1991). Ketepatan diagnosis demam tifoid
dihitung dengan skor:

No

Gejala Klinis

Skor

Demam < 1minggu

Sefalgia (pusing)

Rasa lemah

Mual

Gangguan motilitas saluran cerna

Nyeri perut

Anoreksia

Susah tidur

Splenomegali

Skor Nelwan (2)

No

Gejala Klinis

Skor

10

Hepatomegali

11

Muntah

12

Demam > 1minggu

13

Apatis

14

Lidah tifoid

15

Bradikardi relatif

16

Feses hitam

Skor Maksimal

20

Nilai ramal demam tifoid = skor/20 x 100% menunjukkan persentase kemungkinan terjangkitnya
pasien dengan salmonella typhi atau paratyphi. Dari studi yang dilakukan skor 13 ke atas sudah
mengarah ke diagnosis demam tifoid, sedangkan skor di bawah 7 kecil kemungkinan penderita
terjangkit demam tifoid.

Kesimpulan Penelitian : SENSITIFITAS DAN SPESIFISITAS DIAGNOSIS KLINIS

DALAM
MENDIAGNOSIS DEMAM TIFOID PENDERITA RAWAT INAP DI BANGSAL
PENYAKIT DALAM RSUP SARDJITO (TAHUN 1998-2000)

Sri Wahyuni, Soebagjo Loehoeri, Nurfaita Mislihar

Subbagian Penyakit Tropik dan Infeksi, Bagian Ilmu Penyakit Dalam
FK-UGM/RSUP Dr. Sardjito Yogyakarta
Konas Petri Malang 2005

1. Gejala yang dominan pada kasus demam

tifoid adalah demam, nausea, lidah tifoid dan
bradikardi relatif.
2. Hasil perbandingan diagnosis klinis
terhadap diagnosis laboratoris memiliki
sensitifitas sangat rendah (18,18%), spesifisitas
tinggi (87,5%), nilai ramal positif rendah (25%)
dan nilai ramal negatif tinggi (84%). Berdasarkan
indikator-indikator tersebut dapat dinyatakan
kurang efektif untuk digunakan sebagai

Management :
Suspect Typhoid cases
General Nursing care and Diet
Specific antibiotic therapy
Treatment of Chronic carriers
Management of complications

Antibiotic Therapy :
Chlaramphenicol 4 X 500 mg 11-14 days
Ampicillin 50 -100 mg /kg BW/ day
Trimetropin sulfametoksazole 2 x 2 tab
Ceftriaxone 50 100 mg/ kg BW / day
Cefoperazone 100 mg/kg BW/ day
Cefotaxim 2 3 x 1 gr
Ciprofloxacin 2 x 500 mg
Fleroksasin 1 x 400 mg
Ofloxacin 1 x 600 mg
Perfloxacin 1 x 400 mg
Levofloxacin 1 x 500 mg

DISKUSI
Tabel 1. Perbandingan
(Defervescence)
Demam
Komplikata Fluorokuinolon

Reda Demam
Tifoid
Non-

Nama Obat

Disis

Lama
Pemberian

Penurunan
Demam

Siprofloksasin (5)

500 BID

6 hari

3,60 hari

Ofloksasin (6)

600 mg OD

7 hari

3,40 hari

Pefloksasin (7)

400 mg OD

7 hari

3,10 hari

Fleroksasin (8)

400 mg OD

5 hari

3,40 hari

Levofloxacine (9)

500 mg OD

7 hari

2,43 hari

DISKUSI
Tabel 2. Betalaktam
demam tifoid

untuk

pengobatan

Beta Laktam

Dosis

Lama Pemberian

Ampisilin

4x1 gram IV atau

Oral

Dua minggu

Amoksisilin

50150mg/kgBB/hari

Dua minggu

Sefiksim

10-15mg/kgBB/hari Sepuluh hari

Seftriakson

4 gram/hari

Tiga hari

3 gram/hari

Empat hari

2 gram/hari

Enam hari

DISKUSI
Tabel 3. Berbagai jenis antimikroba untuk
demam tifoid
Antimikroba

Dosis

Kloramfenikol

Hari ke 1 4x250
IV/oral

Lama Pemberian

Hari ke 2 4x500
IV/oral

2 minggu

Kotrimoksazol

2 x 2 tab oral

2 minggu

Azitromisin

2 x 500 mg IV/oral

1 minggu

Aztreonam

3 x 1 gram IV

1 minggu

Multi drugs Resistance Salmonella typhi

(MDRST)

Resistance to :
Chloramphenicol
Amoxycillin
Cotrimoxazole

Komplikasi ( Dikutip dari Butler dan Scheld, 2004)

Abdomen

Perforasi usus terutama ilium , terjadi pada 1- 3 %

Pendarahan saluran cerna, terjadi pada 10 % pasien
Hepatitis
Kholesistitis

Kardiovaskuler

Perubahan elektrokardiografi asimptomatis

Miokarditis
Syok

Neuropsikiatri

Ensefalopati, Delirium, Psikotik, Meningitis

Gangguan Koordinasi

Respirasi

Bronkhitis
Pneumonia

Hematologi

Anemia
Koagulasi intravaskular Diseminata (KID)

Lain lain

Abses Lokal
Faringitis
Relaps
Karier khronis

Penelitian Kompilasi Tifoid dari RS Sanglah Denpasar:

Pada 49 penderita dengan komplikasi tersebut 43 (87,7)
orang datang dengan keluhan utama demam, 38 (77,5)
orang datang ke rumah sakit pada akhir minggu pertama
hingga minggu kedua setelah demam. Sebanyak 7 (14,2)
datang pada minggu ketiga setelah demam. Keluhan
utama penderita lainnya : kesadaran menurun 1 (2,0) ,
nyeri ulu hati 1 (2,0), mual muntah 1 (2,0) dan 3 (6,1)
dengan berak darah. Komplikasi yang terjadi pada
penderita baik intestinal (24,4) maupun ekstra intestinal
(75,5), adapun jenis komplikasi yang terjadi pada
penderita dapat dilihat pada grafik 1.

Tabel 1. Komplikasi demam tifoid di beberapa RS di Indonesia. 5-10

Nama peneliti

Komplikasi

Hendarwanto

Loehoeri

Darmanik

Herdiman

Ratih

(%)

1979

1994

1994

1997

2002

Yogya
Perdarahan
Perforasi
Syok septik
Pneumonia
DIC
Hepatitis
Meningitis
Tifoid toksik
Artritis

14,1
5,4
2,2
2,2
1,1
-

3,07
0,44
4,33
4,38
18,4
-

Denpasar
8
1,8
0,9
7,1
1,8
-

Komplikasi Demam Tifoid Pada Penderita Dewasa di Bangsal Menular

RS Sanglah Denpasar
i.a.ratih wulansari manuaba*, tuti parwati merati**, sjaiful I biran**
**
Divisi Tropik dan Infeksi *Lab/SMF. Penyakit Dalam, FK UNUD/
RS Sanglah, Denpasar Konas Petri Malang 2004

44,4
11,1
16.6
11,1
27,7
-

24,4
16,3
24,4
10,2
36,7
2

> 20 hari

6.1
4

16 - 20 hari

22.4

11 - 15 hari

57.1

6 - 10 hari
10.2

1 - 5 hari

10

20

30

40

50

Lama perawatan penderita dengan

komplikasi.

60

Carriers :
Biliary carriers

Urinary carriers
Intestinal carriers (faecal)
1- 5 % thypoid patient
Problem : cholelitiasis dan
nephrolitiasis

Tifoid carrier treatment

Antibiotic treatment of tifoid carrier fever
Without cholelithiasis complication
1. Ampicillin 100 mg/kgbw/day + probenecid 30
mg/kgbw/day
2. Amoxicillin 100 mg/kgbw/day + probenecid 30
mg/kgbw/day
3. Trimethroprim Sulphametoxazol 2 tabs twice/day

With cholelithiasis complication

Cholesistektomi + regimen above for 28 days, 80 %
curable or cholesistektomi with one of the regimen
below:
1.
Ciprofloxacin 750mg/ twice perday
Cefixime 400 mg bid for 6 days for MDR or non MDR
2.
Norfloxacon 400 mg/ twice /day

Prevention
Decontamination
Louse

: Hospitalization

control:
Bathing and laundering of clothes
in hot water with detergent
Reduction of exposure
Identification and eradication
Prevention of transmission
Protection of the risk infection

Typhoid Vaccines :

1. Parenteral killed whole cell vaccines

* Heat and phenol killed
* Acetone killed and dried
2. Live attenuated Ty21a vaccine
(TYPHORAL@ )
3. Polysaccharide subunit vaccine
(TYPHIM V@)

Vaksinasi Tifoid Tsunami NAD 3-4

Januari 2005

Vaskinasi Tifoid di Tsunami NAD 2-4

Januari 2005

Tsunami NAD 3-4 Januari 2005

TERIMA
KASIH

References :
1. Hohmann, L.E : Approach to the patient with typhoid fever, @2000
UpToDate.www.uptodate.com.(800)998-6374.(781)273-4788
2. Salmonella typhi, From : http://www.medinfo.ufl.edu/year2/mmid/bms5300/bugs/saltyphi.html
3. Material Safety Data Sheet Infections Substances, Section I : Infectious Agent, From :
http://www.hc-sc.gc.ca/pphb-dgspsp/msds-ftss/msds134e.html
4. Typhoid Fever, From : http://www.cdc.gov/ncidod/dbmd/diseaseinfo/typhoidfever_g.htm
5. Ichhpujani, R.L , Bhatia, R : Typhoid Fever, Top Publications, 4093, Nai Sarak, Delhi 110 006,
India, 1997.
6. Zulkarnaen,I : Pola Kepekaan Salmonella typhi terhadap beberapa antibiotika,Demam Tifoid,
Peran Mediator, Diagnosis dan Terapi, Subbgian Penyakit Tropik dan Infeksi FK UI, Jakarta,
2000
7. Suhendro, Inada,K , Hendarwanto, Zulkarnain,I : Patterns of Cytokine and Nitric Oxide in
Typhoid Fever, Demam Tifoid, Peran Mediator, Diagnosis dan Terapi, Subbgian Penyakit
Tropik dan Infeksi FK UI, Jakarta, 2000
8. Nasronudin. Demam Tifoid. Dalam Penyakit Infeksi di Indonesia dan Solusi Kini dan
Mendatang. Edisi ke 2. Airlangga University Press. 2011 , Surabaya. h: 187 -190
9. Nasronudin. Imunopatogenesis, Diagnosis dan Tata Laksana Demam Tifoid Masa Kini.
Dalam Penyakit Infeksi di Indonesia dan Solusi Kini dan Mendatang. Edisi ke 2. Airlangga
University Press. 2011 , Surabaya. h: 191-208

TerimaKasih