DEMAM TIFOID

dr Shahrul Rahman, Sp.PD

Departemen Ilmu Penyakit Dalam
Fakultas Kedokteran
Universitas Muhammadiyah Sumatera Utara

Pendahuluan
Sinonim
Enteric fever
Typhus & parathypus abdominalis

Etiologi

Salmonella typhii
Salmonella paratyphi
A, B dan C

Koloni salmonella
pada agar McConkey.

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

Organism

Salmonella typhi, a Gram-negative bacteria.

Similar but often less severe disease is
caused by Salmonella serotype paratyphi A.
Many genes are shared with E. coli and at
least 90% with S. typhimurium,
Polysaccharide capsule Vi: present in about
90% of all freshly isolated S. typhi and has a
protective effect against the bactericidal
action of the serum of infected patients.
The ratio of disease caused by S. typhi to
that caused by S. paratyphi is about 10 to

Family
Enterobacteriaceae
Motile
Somatic
Flagelar

antigen

Vi

Facultative
anaerobic/aerobic
Gram (-) bacteria

SALMONELLA

Epidemiologi (1)

Penderita 3 % carier
Endemis di Indonesia sporadis
Di Indonesia jarang menjadi epidemi
Penyakit menular dpt mewabah
Dlm 1 rumah kasus jarang > 1
Wajib dilaporkan
Sumber penularan sulit ditentukan

Epidemiologi (2)
Sumber penularan
Air minum / makanan
Tangan :

Tinja sendiri
Urine
Dahak
muntah

Epidemiologi (3)
Daya tahan hidup
Air, es, debu, tinja kering, pakaian
weeks
Kulit 1 minggu
Berkembang dlm susu susu
rusak

Epidemiologi (4)
Distribusi :
Worldwide
Pengaruh iklim tidak ada
> banyak di negara berkembang
di daerah tropis
Pria = wanita
12 - 30 th 70-80 %
Ringan pada anak & glamur

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

Typhoid epidemiology

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 %

Incubation Period : 1 3 weeks

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

Patogenesi
s

Mulut

Usus
Reseptor vili

S. Typhi

Membiak dalam fagosit

mononuklear
jaringan limfoid
Darah (bakteremia
I)
Membiak dlm RES
Darah (bakteremia
II)
Limpa,usus,v. fellea & organ
lain
Ves. Fellea
carrier
Usus

Granulomatosa
Villi, cripte
kelenjar, lam.
propria, kl. limfe
Multiplikasi dalam
fagosit
mononuklear

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

PATOFISIOLOGI

Hubungan Salmonella typhii &

Makrofag
Salmonella
Lewat CR1 & CR3
Fagosom
Lisosom
Fusi fagosomlisosom
Substansi
bakterisidal
Kuman mati

Patologi
Ileum distal
Minggu
I

Radang : hiperplasi plaks

peyeri
Nodul tifoid
Sumbatan pemb.
darah
hipoksia

Minggu II

Nekrose

Minggu III

ulkus

Minggu IV

Penyembuhan tanpa

Perdarahan,
perforasi

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

Dugaan patogenesis
Salmonella typhii
endotoksin
makrofag
Monokins
TNF, Fc antagonis
glucokortiroid, fc
aktivasi limfosit, IF-1

Metabolit,
arakidonat, Ox
radikal
Nekrose sel,
gangguan
vaskuler, depresi
ss. tulang, demam,
abnormalitas lain

Gambaran klinis (1)

Masa tunas : 10 14 hr
Bervariasi
: ringan - berat
Mulai = inf. Akut lain
Minggu I

Demam
Mialgia
Sefalgia
Anoreksia mual muntah
Obstipasi/diare
Abdominal discomfort
Batuk
epistaksis

Gambaran klinis (2)

Minggu II
Gejala > jelas
demam
Bradikardi relatif
Lidah tifoid (tengah kotor, tepi hiperemis,
tremor)
Hepatomegali
Splenomegali
Meteorismus
Gangguan mental : apati, somnolen, stupor,
delirium, koma, psikosis
Roseola jarang

Clinical Manifestations (1):

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

Gambaran klasik demam tifoid

Clinical Manifestations (2):

Anorexia
Nausea
Vomiting
Diarrhea Pea soup stool

Typhoid fever ( enteric fever )

Enteric fever
syndrome

Fever

Chills

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

Laboratorium(1)

Lekosit : lekopeni normal lekositosis

Biakan darah :
Positif
: diagnosis pasti
Negatif : mungkin +/ Tergantung dari

Tehnik

Jumlah kuman 10/cc drh perlu diambil 5-10 cc

R/ sebelumnya
Langsung ditanam kirim
Diambil waktu demam

Saat pemeriksaan

Terbaik minggu pertama selanjutnya

Vaksinasi biakan negatif

R/ antibiotik biakan negatif

Laboratorium(2)

Reaksi widal
Reaksi aglutinasi Ag-Ab
Mencari aglutinin dalam serum
Aglutinin O
(+)
Aglutinin H
(+)
Aglutinin Vi

tubuh kuman : 6 bl
flagella kuman : 1-2 th
simpai kuman

Laboratorium(3)

Fc yg mempengaruhi Rx. widal

Penderita
Gizi buruk
Saat pemeriksaan : minimal mg II peak mg
V
R/ antibiotik
Penyakit penyerta : agammaglobulinemia,
lekemia, Ca advance
R/ immunosupresi / kortikosteroid
Vaksinasi kotipa/tipa
Inf. Klinis/subklinis salmo. Sebelumnya
Rx anamnestis :

Laboratorium(4)

Fc yg mempengaruhi Rx. widal

Tehnis
Rx. Silang dg species lain
Konsentrasi suspensi antigen
Jenis strain salmonella

Widal Test

O antibodies appear on days 6-8 and H antibodies on

days 10-12
Negative in up to 30% of culture-proven cases of
typhoid fever
S. typhi shares O and H antigens with other
Salmonella serotypes and has cross-reacting epitopes
with other Enterobacteriacae, and this can lead to
false-positive results. Such results may also occur in
other clinical conditions, e.g. malaria, typhus,
bacteraemia caused by other organisms, and cirrhosis
This is acceptable so long as the results are
interpreted with care in accordance with appropriate
local cut-off values for the determination of positivity.

Anemia
Leucopenia or leucocytosis
Thrombocytopenia
Abnormal liver function

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

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

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

Penatalaksanan

Perawatan
Diet
Medikamentosa
Cairan & elektrolit

Penatalaksanan
perawatan

Suspek d. tifoid
Tirah baring absolut : dulu

Isolasi
Observasi
Pengobatan
Kesadaran posisi dubah-ubah
Bab & bak diperhatikan

Mobilisasi bertahap (RSCM)

Hari
Hari
Hari
Hari

ke
ke
ke
ke

2 apireksi duduk waktu makan

7 apireksi mulai berdiri
10 apireksi jalan
13-15 apireksi
pulang

Penatalaksanan
perawatan

Suspek d. tifoid
Mobilisasi bertahap (RSWSmakassar)
Hari ke 3 apireksi duduk
Hari ke 7 apireksi jalan
Hari ke 10 apireksi pulang

Penatalaksanan
perawatan

Pola perawatan konvensional : mulai

dengan bubur saring
Lama perawatan 21 hari apireksia

MRS

Hari
perawatan
Mobilisasi
Diet

APIREKSI
A

Baring

Duduk

Jalan

Bubur
saring

Bubur biasa

Nasi

Penatalaksanan
perawatan

Pola perawatan singkat : mulai dengan

nasi
Lama perawatan : 10 hari apireksia

MRS

APIREKSI
A

Hari
perawatan

Mobilisasi

Baring

Duduk

Diet

Nasi

3
Jalan

Penatalaksanan
perawatan

Pola perawatan sangat singkat : mulai

dengan nasi
Lama perawatan : 7 hari apireksia

MRS

APIREKSI
A

Hari
perawatan

Mobilisasi

Baring

Diet

4
Duduk/Jalan

Nasi

Penatalaksanan diet

diet konvensional bubur saring

Maksud bubur saring :

Memudahkan pencernaan/absorbsi
beban kerja usus
Makan kurang merangsang : perdarahan
& perforasi
Netralisasi asam lambung

Syarat bubur saring

Mudah dicerna, porsi kecil, seringkali
Protein cukup
Tidak merangsang
Memenuhi kebutuhan normal

Penatalaksanan diet
Makanan padat
Melancarkan defekasi bulk forming
Supaya BB cepat naik
Sudah jadi bubur di ileum terminalis
Meningkatkan selera makan
Disiapkan : mudah,murah,singkat
Jumlah kalori segera terpenuhi
Lebih menyenangkan penderita
Lamanya perawatan lebih singkat

Pengobatan

Kloramfenikol DOC

Mortalitas < 12 % 1 %
Murah
Kekurangan :

Relaps
Resistensi
Glositis
Lekopeni
Trombositopeni

Pengidap
Mual, muntah
Enterokolitis
Anemi aplastik
Agranulositosis

Dosis :

50 -60 mg/kg.BB tiap 4-6 jam

4 x 500 mg/hr spi 10 hari apireksia

Pengobatan

Rata-rata pulang 14 hr bebas

panas

4 x 250 mg spi 3 hr apireksia

Istirahat 7 hari
4 x 250 mg selama 5 hr
Rata-rata pulang 15 hr apireksia
4 x 400 mg spi 7 hr apireksia
3 x 500 mg spi 7 hr apireksia
Rata-rata pulang 10 hr apireksia

Pengobatan

Tiamfenikol identik kloramfenikol

Dosis :

4 x 500 mg spi 5 hr apireksia

Konsentrasi > dlm darah

> lama dlm badan/empedu
Toksisitas
Kompl. Hematologis

Pengobatan

Ampisilina dan Amoksisilina

Dosis :
2 x 1500 mg = kloramfenikol
3 4 x 1000 mg selama 14 hr

4 x 1000 mg selama 14 hr

2 x 1000 mg selama 21 hr

Rata-rata perawatan 14 hr

Pengobatan

Kotrimoksazole
Dosis :

2 x 2 tablet spi 7 hr apireksia

Ceftriakson
Generasi ke-3 sefalosporin
Dosis :

4 gr /hr selama 2-3 hr

Pefloxacin
Quinolon
Dosis :

400 mg/hr selama 5 7 hr

Pengobatan

Obat-obat lain
Ciprofloxacin 500 mg (single dose)
Ofloxacin 400 mg
Norfloxacin
400 mg

Kortikosteroid
Kontroversi toksis
Membran sel & lisosom hambat
enzym hidrolase
Dosis :

Dexamethasone : 3 mg/kg.BB 1
mg/kg.BB. 6 jam slm 2 hr

Pengobatan khusus

Wanita hamil

Trimester I : kloramfenikol
Trimester III : tiamfenikol
Amoksisilin selalu aman
Kloram pd trimester III tdk boleh
diberi karena :
Partus prematur
Kematian fetus intrauterin
Grey syndrome pd neonatus

Pengobatan khusus

Carierr/symptomless excretor

Tanpa keluhan
symptomless excretor : salmonella (+) dl
feses/urine < 3 bl
Carier > 3 bl
Prev. > 3 %
Usia menengah
Wanita > pria
U/ diagnos : kultur 3-6 x
R/ :

Ampisilin/amoksisilin
: 4 x 1 gr/6 jam
4
mg
Kotrimoksazole
: 2 x 2 tab(480)
4 mg
Ciprofloxacin
: 2 x 750 mg 4 mg
Kombinasi dengan kolesistektomi

Treatment of
uncomplicated typhoid

Oral drugs

Ofloxacin: 15-20 mg / kg for 7-14

days
Azithromycin:8-10 mg/kg for 7
days
Cefixime: 20 mg /day for 7-14 days
Chloramphenicol: 50-75 mg
/kg/day for 14-21 days

Fluoroquinolones

Optimal for the treatment of typhoid fever

Relatively inexpensive, well tolerated and more
rapidly and reliably effective than the former firstline drugs, viz. chloramphenicol, ampicillin,
amoxicillin and trimethoprim-sulfamethoxazole.
The majority of isolates are still sensitive.
Attain excellent tissue penetration, kill S. typhi in its
intracellular stationary stage in
monocytes/macrophages and achieve higher active
drug levels in the gall bladder than other drugs.
Rapid therapeutic response, i.e. clearance of fever
and symptoms in three to five days, and very low
rates of post-treatment carriage.

Chloramphenicol

The disadvantages of using chloramphenicol include a

relatively high rate of relapse (57%), long treatment
courses (14 days) and the frequent development of a
carrierstate in adults.
The recommended dosage is 50 - 75 mg per kg per
day for 14 days divided into four doses per day, or for
at least five to seven days after defervescence.
Oral administration gives slightly greater
bioavailability than intramuscular (i.m.) or intravenous
(i.v.) administration of the succinate salt.

Cephalosporins

Ceftriaxone: 50-75 mg per kg per

day one or two doses
Cefotaxime: 40-80 mg per kg per
day in two or three doses
Cefoperazone: 50-100 mg per kg
per day

Multi drugs Resistance Salmonella

typhi
(MDRST)
Resistance to :
Chloramphenicol
Amoxycillin
Cotrimoxazole

Relapse

5-20% of typhoid fever cases that have

apparently been treated successfully.
A relapse is heralded by the return of fever
soon after the completion of antibiotic
treatment. The clinical manifestation is
frequently milder than the initial illness.
Cultures should be obtained and standard
treatment should be administered.

Pencegahan

Usaha terhadap lingkungan hidup

Penyediaan air minum yg sehat
Sistim pembuangan kotoran yg
higienes
Pemberantasan lalat
Pengawasan thd rumah makan &
penjual makanan

Usaha terhadap manusia

Imunisasi
Menemukan & mengawasi carierr
Pendidikan kesehatan pd masyarakat

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@)

Vaccination

Vi polysaccharide, is given in a single dose

Protection begins seven days after injection,
maximum protection being reached 28 days after
injection when the highest antibody concentration is
obtained.
Protective efficacy was 72% one and half years after
vaccination and was still 55% three years after a
single dose.
In Asian countries where Vi-negative strains have
been reported at the low average level of 3%.

live oral vaccine Ty2la

three doses two days apart on an empty stomach.

Protection as from 10-14 days after the third dose.
> 5 years.
Protective efficacy of the enteric-coated capsule
formulation seven years after the last dose is still
62% in areas where the disease is endemic;
Antibiotics should be avoided for seven days before
or after the immunization

Komplikasi

Intestinal

Perdarahan usus
Perforasi
Ileus paralitik

Ekstraintestinal

Kardiovaskuler
Darah
Paru
Hepar & vesika fellea
Ginjal
Tulang
neuropsikiatrik

Komplikasi : multisystem organ

* Neuropsikiatri
* Perdarahan
* Perforasi
* Miokarditis, Pankreatitis,
* Hepatitis
* Syok septik
Sindrom klinis berupa gangguan kesadaran,
dengan atau tanpa gangguan neurologis, dan
dalam pem. Cairan otak masih dalam batas
normal Tifoid Toksik

KOMPLIKASI
1. INTESTINAL
Perdarahan usus
Perforasi usus
Ileus paralitik

2. EKSTRAINTESTINAL
Kardiovaskular
Hematologi
Paru
Hepar, saluran empedu, pankreas
Ginjal
Tulang, sendi, otot
Neuropsikiatri >>>

Komplikasi
Kardiovaskular
o

Miokarditis 1-5%, paling sering pada

anak-anak
Klinis: takikardia, protodiastolic gallop,
desah sistolik apikal, edema perifer
EKG: perubahan segmen ST dan gel. T,
QT memanjang dan low QRS voltage
Bisa menimbukan abses miokarditis, jika
ruptur tamponade jantung

Trombi mural
Emboli sistemik dan pulmonal
Aneurisma
Perikarditis
Kolaps vaskular perifer>>
Trombosis vena dan arteri.

Komplikasi Darah

Anemia >>. Khosla 80% kasus, morfologi

normositik normokrom, 2 pasien mikrositer
hipokrom, anemia hemolitik 1 pasien.
Hongkong; G6PD Def. atau
hemoglobinopathi
Lekopenia dan limfositosis relatif jarang
Lekositosis
Trombositopenia (Jakarta 61,5%)

Perdarahan akut
Hemolytic uremic syndrome (HUS)
Koagulasi intravaskular diseminata

Komplikasi Paru

Stadium awal ; bronkitis

typhoid lobar pneumonia
(pneumo-typhoid)

jarang (minggu II/III)

1-3%

Efusi pleura
Pneumothrax
empiema
Abses paru <<<

Komplikasi hepar, kandung

empedu dan pankreas
Tifoid hepatitis asimptomatis
Hepatomegali
Kriteria tifoid hepatitis menurut Khosla :
1. Hepatomegali
2. Ikterus
3. Kelainan lab (Bilirubin > 30,6umol/l, SGOT/SGPT
meningkat, indeks waktu protrombin menurun)
4. Kelainan histopatologi
:3 atau lebih gejala : Hepatitis tifosa

 Pohan

dkk (Jakarta): 4,8% kasus,

Suling dkk (Manado) 6,2%
Nelwan RHH; Pankreatitis tifosa
Kolesistitis akut
Kolesistitis kronik

Komplikasi Renal

Fungsional atau patologis

Akibat gangguan glomerulus
sementara atau GGA karena
hemolisis
Khosla typhoid-nephritis 0,7%,
proteinuria 61,34%, pyuria 22%
Pohan dkk 75,2% proteinuria,
lekosituria 5,7%

Retensi urin
glomerulonefritis
Pielonefritis
Sistitis
Orkhitis
Basiluria asimptomatis stadium dini

Imune complex-mediated
glomerulonephritis thypoid-

nephritis / nephrotyphoid

Komplikasi
neuropsikiatri
Paling

sering
Insiden berbeda-beda tiap negara
Khosla ; 36,7%
Indonesia dan Vietnam 10-40%

Komplikasi lainnya :
depresi
tuli
transverse myelitis
gangguan ekstrapyramidal
pseudo tumor cerebri

Komplikasi tulang,
sendi dan otot

Typhoid osteomyelitis
Typhoid spine (diagnosa banding
tbc)
Typhoid arthritis
Insiden 2%
Periostitis
Ruptur otot

Komplikasi lain-lain
Hiperkalsemia
ulserasi dekubitus
Parotitis
Alopesia
Furunkulosis
Spontaneus spleen rupture
Abortus

DEMAM TIFOID BERAT

=> Sindroma klinis berupa gangguan
atau penurunan kesadaran akut
(kesadaran berkabut, apatis, delirium,
sopor dan koma) dengan atau tanpa
disertai kelainan neurologis lainnya.
= Demam Tifoid Toksik, Demam
Tifoid ensefalopati, Demam Tifoid
dengan toksemia

Patofisiologi belum jelas

Hornick dan Greisman; endotoksin
toksemia

inflamasi makrofag monokin,

asam arakhidonat, radikal bebas
Demam Tifoid Berat

PENGOBATAN
ANTIBIOTIKA
PERAWATAN

YANG BAIK

NUTRISI
CAIRAN

DAN ELEKTROLIT
PENCEGAHAN KOMPLIKASI
KORTIKOSTEROID ?

ANTIBIOTIKA
Kloramfenikol (500 mg / 6 jam selama 14
hari) dapat menurunkan angka kematian
dari 10-15% menjadi 1-4% resisten, tidak
efektif terhadap karier, aplastik anemi
Amoxysillin 1 gr/8 jam selama 14 hari
Ampicillin
Cotrimoxazole
Tiamfenikol

 Fluorokuinolon

paling efektif,
waktu singkat, pilihan pertama,
angka stool carriage lebih rendah
Azithromycine
Sefalosporin generasi ketiga

Penanganan Demam Tifoid Berat

Makanan (tinggi kalori dan rendah
serat) melalui IV atau sonde
Mencegah dan mengawasi
perforasi, perdarahan dan syok
Keseimbangan cairan dan elektrolit

Pada keadaan adanya komplikasi

(renal, kardiovaskular, Pernafasan,
neuropsikiatri, tulang, hematologi)
=> Prosedur medik yang berlaku

Treatment of severe
typhoid

Kortikosteroid

Kontroversial
Hoffman dkk; deksametason menurunkan
angka kematian 55,6% menjadi 10%
Gaol LM (Medan); pemberian
deksametason dosis tinggi dan rendah
tidak ada perbedaan bermakna
Widodo (Jakarta); Deksametason 3 X 5 mg
hasil klinis sama dengan dosis tinggi
Hook ; tidak setuju pemberian
kortikosteroid (banyak efek samping)

Dexamethasone for
CNS complication

Should be immediately be treated with

high-dose intravenous dexamethasone
in addition to antimicrobials
Initial dose of 3 mg/kg by slow i.v.
infusion over 30 minutes
1 mg/kg 6 hourly for 2 days
Mortality can be reduced by some 8090% in these high-risk patients

Prognosis

Umur
Kekebalan penderita
Juml. & virulensi salmonella
Cepat & tepatnya terapi
Keadaan umum

Differensial diagnosa

Influenza
Disentri basiler
Peny. Dgn demam yang lama
Malaria
tuberkulosis