dr.

Christina K Nugrahani, MKes,

SpA
 Enteric fever is a systemic syndrome
produced by certain Salmonella organism.
It encompasses:
 Typhoid fever caused by SALMONELLA
TYPHI
 Paratyphoid fever caused by S. Paratyphi A,
B, C

Typhoid Fever, the most frequent enteric fever,

tends to be more severe than the other forms
 EPIDEMIOLOGY
 The incidence, mode of transmission, and
consequences of enteric fever differ
significantly in developed and developing
countries.
 In USA: the annual incidence < 0,2 / 100.000
 In developing countries, the incidence can
reach 500 / 100.000 (0,5%) and a high mortality
rate.
 The WHO has estimated that 12,5 million cases
occur annually worldwide.
  The incubation period : 7-14 days
 The clinical manifestation :
FEVER MALAISE ANOREXIA
MYALGIA HEADACHE ABDOMINAL PAIN
VOMITING DIARRHEA

If no complications occur,
the symptoms and physical findings
resolve within 2-4 weeks
 Blood cultures positive in 40-60%
Stool & urine cultures become positive after
the first week
A culture of bone marrow is the single most
sensitive method of diagnosis (positive in
85-90%)
 Immunologic methods: direct detection of S. typhi
specific antigens in the serum or in the urine
 PCR specific and more sensitive than blood
cultures
 The Widal test measures antibodies against O and H
antigens of S. typhi
 normochromic normocytic anemia
is related to intestinal blood
loss
or bone marrow supression
 leukopenia
 thrombocytopenia
 CHLORAMPHENICOL remains the gold
standard.

50 mg/kg/D p.o OR 75 mg/kg/D iv in 4

equal doses
Most children become afebrile within 7 days
Treatment of uncomplicated cases should be
continued for at least 14 days,
or 5-7 days after defervescence
 AMPICILLIN 200 mg/kg/D iv in 4-6 doses
 AMOXICILLIN 100 mg/kg/D p.o in 3 doses
 TMP-SMX (10 mg of TMP and 50 mg of
SMX/kg/D p.o in 2 doses)
 CEFIXIME 20 mg/kg/D in 2 divided doses for
8 days
 CEFTRIAXONE 50 mg/kg/D i.m for 5 days
 OFLOXACIN 15 mg/kg/D for 2 days
• Intestinal perforation has been observed in 0,5 - 3%
and severe hemorrhage in 1-10%.
Perforation rarely occurs without preceding
hemorrhage the site is usually in the lower ileum
• A toxic encephalopathy or cerebral thrombosis may
also occur.
• Pneumonia is caused by
a superinfection related to
organisms other than Salmonella.
Dependent upon:
 the patient’s age and previous state of health
 the type of complications that may occur
Therapy with Chloramphenicol has reduced the
mortality rate to less than 1 % in most areas.
The presence of perforation of the GI tract or severe
hemorrhage increases the chances of death.
Morbidity and mortality may also be related to the
development of meningitis or endocarditis.
Widal Agglutination Test –
Over 100 Years:
Remain Plagued by Controversy
 Demam Enterik
Insidensi

• Diperkirakan 16.000.000 kasus di seluruh

belahan bumi, 7.000.000 berasal dari daerah
endemik Asia Tenggara

Kematian

600.000 Masalah Diagnosis

Penderita Besar dan Pengelolaan
Dini
 Diagnosis
Klinis: sulit, manifestasi klinis jarang spesifik
Laboratoris:
Kultur:
Sumsum tulang: 85-95%, invasif  tidak rutin
Darah: - 40-60%, terutama minggu pertama
- Afifi et al.:
10.130 penderita AFI 5% Demam Tifoid
3% Brucellosis
Am J Trop Med Hyg. 2005;73(2):392-399

Tes Serologi:
- Uji Widal: still in common use
- Lain-lain: Elisa, Immunobloting, dot immunobinding, dipstick
belum diterima luas
Zaniga et al. J Clin Micr. 2005;45(9):4545-4550
 UJI WIDAL

• Widal & Secard, 1896

• Dasar: adanya aglutinin terhadap O dan H antigen
dari Salmonella

•Teknik
–Slide Test:- hasil cepat
- prosedur skrining
–Tube Agglutination Test
–1936, Welch: Validitas rendah dibanding kultur

71 tahun berlalu: Uji Widal masih sering diminta

Penyebab Hasil Negatif Uji Widal:

• infeksi oleh S. typhi/paratyphi

• ‘Carrier’

• ‘Inoculum size’: tidak adekuat

• Pengaruh pemberian antibiotik (?)

• Kesulitan teknik

• Variabilitas dalam penyediaan antigen komersial

Penyebab Hasil Positif Uji Widal:

• Penderita dengan infeksi S. typhi/paratyphi

• Imunisasi dengan antigen Salmonella

• Reaksi silang dengan: - non typhoidal salmonella/

enterobakteria lain

• Tidak ada standardisasi antigen komersial

• Infeksi lain: malaria dan virus dengue

 Alasan Permintaan (UNDERSTANDING)

1 Tidak tersedia sarana kultur

2
1 Memerlukan jawaban yang cepat
Widal: 45 menit
Kultur: 3-7 hari

3 Tidak tersedia data titer aglutinin di daerah endemis

Pengajaran: tidak ada ketegasan

Tidak terlarang

• Usually a single agglutinin titer of 1:320 or greater

for antibody to the O antigen alerts the physician to
consider Typhoid Fever
Cleary TG and Pickering LK. Acute Gastroenteritis in Krugman’s
Infectious Disease of Children, 1992

• The classic Widal test: because many false positive

and false negative results occur, diagnosis of
Typhoid Fever by Widal test alone is prone to error
Cleary TG. Enteric Fever in Nelson Textbook of Pediatrics, 17th ed., 2004
• The Widal test measures antibody against the O
and H antigen of S. Ser. typhi although many
patients with enteric fever may have four fold rise in
the titer, both false positive and false negative
results occur
Cleary TG: Salmonella in Feigin, Cherry, Demmler, and Kaplan Textbook
of Pediatric Infectious Disease, 2004
 Widal Test in Diagnosis of Typhoid Fever in Turkey

Willke A, Ergonul O, and Bayar B. Clinical and

Diagnostic Laboratory Immunology 2002,9(4):938-941

… We conclude that O and H agglutinin titers of ≥1/200 are

of diagnostic significance …
 TUBEX ® TF

Tes Diagnostik Tifoid

dari IDL

A Rapid Detection of Typhoid Fever

JAWABAN PASTI
DIAGNOSA
TYPHOID
 HASIL
SEMI KUANTITATIF
 Sensitifitas Tubex TF 100 %
 Spesifisitas Tubex TF 90 %
(Surya H dkk; FKUI, 2006)

Akurat
Inovatif
 Metode Inhibition
Magnetic Binding
Immunoassay
 Desain well canggih
berbentuk V
Mudah  Tes Tubex TF
Tidak
membutuhkan
keahlian
khusus.
 Prosedur
Tubex TF tidak
rumit
 Tubex TF
hanya 3
langkah
penetesan
Mudah
Praktis
 Semua keperluan tes
Tubex TF sudah
tersedia
 Tes Tubex TF tidak
perlu ELISA reader
 Tubex TF Bisa
dikerjakan dimana
saja
 Cepat
 Waktu pengerjaan
Tubex TF sampai
mendapatkan hasil
kurang dari 15 menit
Terpercaya
 Tubex TF menggunakan
antigen O-9 LPS S.typhi
yang dimurnikan
 Sudah ada evaluasi klinis
Tubex TF di
mancanegara dan di
Indonesia
 Tubex TF telah
memenuhi persyaratan
penggunaan di Eropa
(Logo CE)
Tubex TF Clinical Evaluation in Indonesia

“TUBEX TF Test Compared to

Widal Test in Diagnostic of
Typhoid Fever”

Surya H*, Setiawan B*, Shatri H**, Sudoyo A***, Loho T****

*Tropic Infection Division, **Division of Psychosomatic

***Division of Hematology-Medical Oncology, Department of Internal Medicine

***Division of Clinical Pathology

Faculty of Medicine University of Indonesia

Tubex TF Clinical Evaluation in Indonesia

BACKGROUNDS
 Diagnosis of typhoid fever is still a health
problem in Indonesia.
 Blood culture of S. typhi which was
regarded as gold standard only positive in
40-70% of cases suspected as typhoid
fever.
 PCR as another diagnostic tool can not be
widely used because of its expensive and
limited facilities.
Tubex TF Clinical Evaluation in Indonesia

BACKGROUNDS
 Widal test which is widely used because of
cheap and easy to perform is influenced
by many factors, so it has only 60-80%
sensitivity and specificity.
 So we need another serologic test which
can give rapid and accurate results but is
also high sensitivity and specificity.
Tubex TF Clinical Evaluation in Indonesia

BACKGROUNDS
 TUBEX®TF is one of several new
serologic test that has been studied in
several countries and proved to have high
sensitivity and specificity result but it is not
yet studied in Indonesia.
Tubex TF Clinical Evaluation in Indonesia

OBJECTIVES
To study sensitivity and specificity
TUBEX®TF test compared to Widal
test in diagnosis of typhoid fever
which are already confirmed by PCR
and or blood culture.
Tubex TF Clinical Evaluation in Indonesia

METHODS
 We collected inpatiens with suspected typhoid
fever (according to Nelwan’s typhoid score >/=8)
from Dr. Cipto Mangunkusumo Hospital,
Persahabatan Hospital and Tangerang Hospital.
 Patients were interviewed, physically examined,
taken blood sample for Widal, S. typhi culture,
PCR S. Typhi and TUBEX®TF test.
 Data were processed with SPSS13 statistical
programme and plotted in frequency table and
cross table.
Tubex TF Clinical Evaluation in Indonesia

RESULT
 From May - October 2006, we collected 54
samples that fulfilled the requirement criteria, but
2 samples were excluded because of icteric
samples. The 52 samples consisted of 27 (52%)
males and 25 (48%) females with the highest
frequency of age is 20-30 years old (53.8%).
Tubex TF Clinical Evaluation in Indonesia

RESULT
 Result of TUBEX®TF compared to Widal
test in diagnosing typhoid fever i.e:
sensitivity 100% and 53.1%, specificity
90% and 65%, Positive Predictive Value
(PPV) 94.11% and 70.8%, Negative
Predictive Value (NPV) 100% and 46.4%,
positive likelihood ratio 10 and 1.51,
negative likelihood ratio 0 and 0.72.
Tubex TF Clinical Evaluation in Indonesia

RESULT
 Compared to Widal test, the TUBEX®TF test
was found to be significant (p<0.05) using Chi
square statistical test.
Tubex TF Clinical Evaluation in Indonesia

CONCLUSION
 TUBEX®TF test is more sensitive and
specific than Widal test in diagnosing
typhoid fever.