Professional Documents
Culture Documents
Clinical, Laboratory
Laboratory
Diagnosis
Diagnosis and
and Management
Management
of
of Typhoid
Typhoid Fever
Fever
Sudirman Katu
Division of Tropical Medicine and Infectious Diseases
Departement of Internal Medicine
Faculty of Medicine
Hasanuddin University/General Hospital of Wahidin
Sudirohusodo
Alexander The Great died when he was 34 years old due to acute fever
illness possibly due to typhoid fever or malaria
DEFINITION
Typhoid Fever
Salmonella
Enteric Fever and Paratyphoid Salmonellae:
Salmonella typhi
Salmonella paratyphi A
Strongly endemic
Endemic
Sporadic cases
Developed Countries:
Good sewage and water supply system
Most cases are sporadic or imported or can
Developing World:
Endemic
Peak in hot dry months or rainy season
The incidence of typhoid fever is 2- 3
Typhoid fever
ETIOLOGY
Salmonella:
Structure, Classification, & Antigenic Types
1. Gram-negative, flagellated and facultative anaerobic
bacteria
2. The cell envelope contains a complex
lipopolysaccharide (LPS) structure. (an outer Opolysaccharide coat, a middle portion, the R core, and
an inner lipid A coat)
3. This LPS structure is thought as an endotoxin, and
important in determining virulence of the organisms.
Toxin production
S. typhi contains ;
Serotype
S. paratyphi A
S. paratyphi B
S. stanley
S. saintpaul
S. agona
S. typhimurium
S. paratyphi C
S. choleraesuis
S. virchow
S. thompson
S. typhi
S. enteritidis
S. dublin
S. gallinarium
Method of Transmission
Transmission
stomach
(mono
nuclea
r
phago
cytes )
Bac. In gall
Bac. In
feces
Lower
ileum
3-4w
thoracic
duct
1st bacteremia
(Incubation stage)
10-14d
S.Typhi eliminated
convalvescence stage
(4-5w)
sum (n=119)
59
57
108
41
118
14
37
84
104
91
117
109
109
117
117
%
94.9
94.7
90.7
90.2
89.8
78.6
78.4
41.8
57.7
46.2
34.2
32.1
33.9
12.3
0.8
Symptoms
Symptoms usually develop 13 weeks after exposure,
and may be mild or severe
FIRST WEEK:
High fever 103 or 104 F (39.4 or 40 C)
Malaise
Headache
Constipation (adults) or diarrhea (children)
Rose-colored spots on the chest
Enlarged spleen and liver
Healthy carrier state may follow acute illness
17
Symptoms
SECOND WEEK:
Become delirious
Symptoms
FOURTH WEEK:
Improvement may come slowly during the fourth
week
Fever is likely to decrease gradually until your
temperature returns to normal in another week to
10 days
Signs and symptoms can return up to two weeks
after fever has subsided
19
Typhoid Specialties
Fever pattern in Typhoid Fever
High fever
Headache
Abdominal discomfort
Diarrhea or constipation
Relative bradicardia
Leucopenia
Mild thrombocytopenia
Relative neutrofilia
Aneosinofilia
14
Diagnosis
Diagnosis of typhoid fever is made by
Clinical examination
Blood, bone marrow, or stool cultures for
S. typhi
Serological Tests
Laboratory Examination
Peripheral blood count
leucopenia,
thrombocytopenia
aneosinophilia
Inflammatory
increased CRP
Serum transaminase
Serology
Widal,Typhidot
Tubex (Salmonella IgM)
Blood culture
PCR
Salmonella typhi
Serodiagnosis of Typhoid :
1.Detection of Antibodies in serum:
1.Widal test (Tube or Slide),
3.Tubex system,
2.Typhidot assay
4. Dipstick assay.
2. CIE,
4. Co-agglutination
Widal test
O (somatic) antigens
LPS in the cell wall;
Heat stable
Less immunogenic
H (flagella) antigens
Present in flagella;
Heat labile;
Strongly immunogenic;
Induce rapid & High Ab titres;
Agglutination with antisera:
Large, loose, cotton wool
clumps
Vi (virulence) antigen
Capsular polysaccharide expressed on certain serotypes
Heat labile;
Poorly immunogenic, BUT antibodies are protective:
1.
2.
3.
WIDAL Test
I st week negative.
Titers raise in 2nd week
Raise of titers is diagnostic
26
2.
3.
4.
Early treatment,
Relapses of typhoid fever.
Occasionally the infecting strains are poorly
immunogenic.
Duration of
diseaseS
Specimen
examination
%positivity
1st week
Blood culture
90%
2nd week
Blood culture,
75%
Faeces culture
50%
Widal test
Low titre
Widal test
80-100%
Blood culture
60%
Faeces culture
80%
3rd week
PRODUCT
PRODUCT PERFORMANCE
PERFORMANCE
Karen H Keddy, Arvinda Sooka, Maupi E Letsoalo, Greta Hoyland, Claire Lise Chaignat, Anne B Morrissey & John A Crump (2011). Sensitivity and
specificity of typhoid fever rapid antibody tests for laboratory diagnosis at two sub-Saharan African sites. Bulletin of WHO, vol 89 (9);p.640-647
(Pak-Leong Lim,et al,, 1998. One-Step 2-Minute Test to Detect Typhoid-Specific Ab Based on Particle Separation in Tubes. Journal of Clinical
Microbiology, August 1998, p. 2271-2278, Vol. 36, No. 8)
tc
PRODUCT
PRODUCT PERFORMANCE
PERFORMANCE
Comparative performance analysis of 4 serological tests for S. typhi.
Test kit
Sensitivity
95% CI
Specificity
95% CI
PPV
NPV
TUBEX
IgM (n=177)
94.7%
(86.2-98.3)
80.4%
(71.1-87.3)
78.0%
95.3%
SD Bioline (n=150)
IgM
IgG
69.0% (55.3-80.1)
70.7%(57.1-81.5)
79.3%(69.4-86.8)
76.1%(65.9-84.1)
67.8%
65.1%
80.2%
80.5%
TYPHIDOT (n=177)
IgM
IgG
54.7%(42.8-66.1)
73.3%(61.7-82.6)
64.7%(54.6-73.7)
46.1%(36.3-56.2)
53.2%
50.0%
66.0%
70.1%
90.7%(81.1-95.8)
96.0%(88.0-99.0)
49.0%(39.1-59.1)
39.2%(29.0-49.4)
56.7%
53.7%
87.7%
93.0%
Razel L. Kawano, et al 2007. Comparison of Serological Test Kits for Diagnosis of Typhoid Fever
in the Philipines. J Clin Microb, 246-247.
tc
PRODUCT
PRODUCT PERFORMANCE
PERFORMANCE
Score
< 2
Interpretation Guide
NEGATIVE - Does NOT indicate current typhoid fever
infection
Borderline, inconclusive score.
Repeat analysis. If still inconclusive, repeat sampling at a
later date.
4-5
> 6
INDETERMINATE
tc
Treatment
Manifestations
Poor intake
Toxic typhoid
Perforation symptoms
TREATMENT
General :
Symptomatic : antipyretic
Treatment
Pharmacologic
Symptomatic
Antibiotic :
Cephalosporin
: Ceftriaxone
3-4 g/days
Ampicillin/Amoxicillin : Ampicilin/Amoxicilin
4x500mg
Chloramphenicol
: Cholramphenicol 4x500mg
Fluoroquinolones
:
Ciprofloxaxin
2x500 mg
Ofloxacin
2x400 mg
Pefloxacin
1x400 mg
Levofloxacin
1x500mg
Macrolide
: Azithromycin
1x500mg
Post
Embryonic
period**
Peripart
al
period**
*
Lactatio
n
Penicillin
None known
Cephalospori
ns
None known
Aminoglycosid
es
Erythromycin
(+)
Clindamycin
(+)
(+)
(+)
(+)
Tetracyclines
Chloramphenic
ol
Co-trimoxazole
(+)
(+)
Fusicid Acid
(+)
None known
Rifampicin
Vancomycin
(+)
(+)
(+)
(+)
Quinolones
(+)
Agent
Nitrofurantoin
Metronidazol
e
Contraindicated or
Anot recommended
(+)
+ safe for use
A
when indicated
None known
Disturbance of chodral growth
** Postembryonic period (13th to 39th wk. of pregnancy) *** Peripartal period (40th wk. of
A(+)
A(+)
Complications
Intestinal complication
intestinal perforation
gastrointestinal hemorrhage
hepatiitis, pancreatitis, paralytic ileus
Rujuk
Extraintestinal
Cardiovascular : shock, myocarditis
Neuropsychiatric : encephalopaty, delirium
psychosis
Respiratory : bronchitis, pneumonia, pleuritis
Hematology : anemia, DIC
Kidney : glemerulonephritis, pyelonephritis
Others : osteomyelitis, focal abscess
Chronic Carrier:
No Gall-Stones:
Presence of Gall-stones:
Dexamethasone
Prevention - General
Prevention - specific
Prognosis:
Prophylaxis
Wash your hands.
Avoid drinking
untreated water.
Avoid raw fruits and
vegetables
Choose hot foods.
Conclusions
Terima Kasih
Bila kita curiga dengan Demam tifoid, maka kita lakukan pemeriksaan
penunjang seperti
Widal. Hasil nya positif, lalu kemungkinan diagnose demam tifoidnya
adalah
Kita lihat prevalensi nya adalah 47% (0,47)., selanjutnya kita konversi
ke nilai odds,
Odds = P / (1-P) = 0,47 / (1-0,47) = 0,89. Sehingga nilai odds demam
tifoid dari hasil widal :
Pre-test Odss X LR+ = 0,89 X 6,5 = 5,76 (kita sebut post test odds).
Maka probabilitas terjadinya demam tifoid = odd / (odds+1) = 5,76 /
6,76 = 0,85 atau 85%
Tubex TF. Hasil nya positif, seperti halnya widal;
Odds = 0,89. post test odds = 0,89 x 5,8 = 5 dan Probabilitasnya
adalah = 5/6 = 83%
Typhoid Dot. Hasilnya positif;
Odds = 0,89 Post test odds = 0,89 x 7,9 = 7 sehingga
probabilitasnya = 7/8 = 0,88 = 88%
Blood Culture. Hasilnya positif.
Odds = 0,89 Post test odds = 0,89 x 5 = 4,45 sehingga
probabilitasnya=4,45/5,45 = 0,82% atau 82%