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. dr Soroy Lardo, SpPD FINASIM
Pangkat/Nrp : Kolonel 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
Spesialis Penyakit Dalam Fakultas Kedokteran USU 2005
Program Doktor Fakultas Kedokteran UGM : 2016
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

*
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 Int’l Ed. 1995;1173-9.
 Clinical Patterns of Infection
1. Enteric fever (typhoid fever), due to serotype
typhi.
2. Acute enterocolitis, caused by serotype
typhimurium.
3. Septicemic type, due to serotype choleraesuis,
characterized by :
- bacteremia
- focal lesions
This is responsible for 75% of reported cases of food poisoning in UK
 Indonesia :760-810 cases / 100.000 people with death rate 3.1-10.4 %
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 16 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 Chronic carrier

Stool
Vomit
Indirect Urine Direct
Infection Infection
> 90 % < 10 %

Infected
Healthy
Water
subject
Food

Typhoid
fever
 Faktor Penentu
Virulensi Salmonella
thypi

Somatik (O) ada 2 determinan

Antigen (endotoksin – LPS, Capsular Vi (Polysaccharide (Vi) ada
aceltylated glucosamine 2 determinan antigen (O)- acetyl – N
dissaccharide lipid A acetyl carboxyl)

Flagella protein (H) Outer Membran Proteins (OMPS)

antigen (fase 1 dan II)

Porin (Omp B,C,D Non Porin

dan OmpR)
 BAKTEREMI
Patofisiologi A1
(24-72jam)

Masuk PD
Makanan Duktus ke RES Kapsul Vigagal
yg Torasikus (hati, limpa, fagositosis 
tercemar SST) Replikasi pesat (7-
10hari)

Menembus Kelenjar Ke
mukosa limfe usus Pembuluh
usus (replikasi) darah BAKTEREMI
A2
 Bakteremia ke-2

Endotoksin C3a,
(LPS) C5a
pirogen
T-helper
Sel Plasma & IL 2 IL-1
Limfosit B
Agglutinin O Hipotalamus
Sel Plasma & demam
Limfosit B Limfosit T
Agglutinin H &
Agglutinin Vi

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)

3
4. Outer Membrane Protein (OMP)

4
1
 S typhi
Resists the low pH of stomach

Reach SMALL
INTESTINE Salmonella next penetrate the mucous
Membrane bound vacuoles enterocytes,
SpiC layer of the gut

Bac must survive the antimiCrobial Bacterial proteins mediate in the ACTIN,
environment of macrophage, which a-actinin, trombomyosin, talin
includes the production of
antimicrobial peptides and hydrolytic
Microfold cell (M cell)
enzyme
Peyers patches, multiply in
mononuclear phagocyte

Spread to the phagocyte of the liver,

gallbladder & spleen

Bacteremia, endotoxin release

Cytokines, IL16, IL6, TNF-alfa, TNF-
R, p55

Clinical manifestation
Incubation Period : 3 – 60 days
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 Fever Chills

syndrome
Headache Malaise Abdominal pain
Anorexia Weight loss weakness
Rose spots DIC Hepatomegaly
Splenomegaly Bacteremia 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 Week2
Week1
Week3 Week4 Chronic
periode
10-12 days
S. Typhi 
Mouth  Relaps or
Peyer’s patch 
Blood stream 
Carrier
V.Velea 
Intestine 
Peyer’s patch
Tripple Cross

Normal --- Blood pressure --- Temperature

--- Pulse

Adapted from Syafruddin ARL RSPAD 2005

 Pathogenesis :

Ingestion of S.typhi Enter the small intestine

Excreted in stool MULTIPLI Infection carried in the

and Urine CATION Lymphoid follicle

Inflammation, necrosis, Draining mesenteric

Ulceration Payer’s patches Lymph node

Liver, GB, Spleen,BM Entering thoracic ducts

Multiply within MNPC Passed through the heart

End incubation period

Secondary bacteremia Primary bacteremia

 Pathology :

Payer’s 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
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
Anemia
Leucopenia or leucocytosis
Thrombocytopenia
Abnormal liver function
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

1 Demam < 1minggu
1
2 Sefalgia (pusing)
1
3 Rasa lemah
1
4 Mual
1
5 Gangguan motilitas saluran cerna
1
6 Nyeri perut
1
7 Anoreksia
1
8 Susah tidur
1
9 Splenomegali
1
 Skor Nelwan (2)
No Gejala Klinis Skor
10 Hepatomegali
1
11 Muntah
1
12 Demam > 1minggu
2
13 Apatis
2

14 Lidah tifoid
2
15 Bradikardi relatif
2
16 Feses hitam
2
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
pegangan diagnosis. Perlu pendukung yang lain yaitu dengan
pemeriksaan laboratoris.
 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 Reda Demam (Defervescence)
Demam Tifoid Non-Komplikata Fluorokuinolon
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 untuk pengobatan demam tifoid
Beta Laktam Dosis Lama Pemberian

Ampisilin 4x1 gram IV atau Oral Dua minggu

Amoksisilin 50-150mg/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 Lama Pemberian

Kloramfenikol Hari ke 1 4x250 IV/oral

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.
 10,2 2,1 Hepatitis tifosa
16,7
24,4 Perdarahan usus
Tifoid toksik
Pneumonia
Meningitis
36,7 24,4 Artritis
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 Denpasar

Perdarahan 14,1 3,07 8 44,4 24,4

- 0,44 1,8 11,1 -
Perforasi
5,4 4,33 0,9 - -
Syok septik
2,2 4,38 7,1 16.6 16,3
Pneumonia
2,2 - - 11,1 -
DIC
1,1 18,4 1,8 27,7 24,4
Hepatitis
- - - - 10,2
Meningitis
- - - - 36,7
Tifoid toksik
- - - - 2
Artritis

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

 > 20 hari 6.1

16 - 20 hari 4

11 - 15 hari 22.4

6 - 10 hari 57.1

1 - 5 hari 10.2

0 10 20 30 40 50 60

Lama perawatan penderita dengan komplikasi.

 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
2. Norfloxacon 400 mg/ twice /day

Cefixime 400 mg bid for 6 days for MDR or non MDR

Prevention
Decontamination : Hospitalization
Lousecontrol:
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