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Mochammad Hatta@2013
Mochammad Hatta@2013
Mochammad Hatta@2013
CLINICAL PICTURE
Symptoms begin with sudden onset of highgrade fever, headache & dry cough.
Fever is swinging or may show step ladder
pattern & patient initially feel well & mobile.
Abdominal pain & toxicity follow soon & by
the end of 1st week spleen is palpable & pink,
discrete, skin rash appears over the trunk.
Constipation is more common than diarrhea
which is usually greenish in color (pea soup).
Mochammad Hatta@2013
CLINICAL PICTURE/2
Abdominal tenderness & hepatomegaly occur
in 50% of patients.
The pulse is relatively slow in relation to fever
(Paget sign).
The tongue is coated with free margins &
halitosis may be present.
The sweat of some patients smell like yeast.
Mochammad Hatta@2013
CLINICAL PICTURE/3
The 3rd week of illness is the usual time for
complications in the untreated patients.
Local gut as well as systemic
complications may occur.
Serious infections may progress rapidly to
drowsiness & coma which is usually fatal
(coma vigil).
Mortality is unlikely after the 4th week &
patients may become carrier if not treated.
Mochammad Hatta@2013
Typhoid fever
Paratyphoid fever
Mochammad Hatta@2013
LOCAL COMPLICATIONS
Intestinal hemorrhage
Intestinal perforation
Paralytic ileus
Zenker degeneration of abdominal muscles
Mochammad Hatta@2013
SYSTEMIC COMPLICATIONS
Endocarditis
Arteritis & arterial emboli
Cholecystitis
Hepatic & splenic abscesses
Pneumonia or empyema
Osteomyelitis & septic arthritis
Meningitis
Urinary tract infection
Mochammad Hatta@2013
Mochammad Hatta@2013
Typhoid fever
Laboratory diagnosis
------------------------- 3
____
tambah Taq polymerase <>
dNTPs
_____________
--------------------------3
3'___________<>____
<>_________
Mochammad Hatta@2013
Mochammad Hatta@2013
Typhoid fever
(nested)
ST1 : 5-ACT GCT AAA ACC ACT ACT-3
ST2 : 5-TTA ACG CAG TAA AGA GAG-3
ST3 : 5-AGA TGG TAE TGG CGT TGC TC-3
ST4 : 5-TGG AGA CTT CGG TCG CGT AG-3
(M. Hatta & Henk L Smits. Annals Tropical
Medicine & Parasitology (Liverpool), 2006)
Mochammad Hatta@2013
Mochammad Hatta@2013
Indonesia
Mochammad Hatta@2013
941 bp
819
639
310
Mochammad Hatta@2013
PCR for the detection of S. typhi specific DNA in blood, stool and urine
samples from patients with suspected typhoid fever .
Patient group
Culture positive
Culture negative
1 (1) 71 (99)
21 (45) 26 (55)
16 (67)
7 (41)
2 (100)
Mochammad Hatta@2013
8 (33)
10 (59)
0 (0)
22 (38)
11 (28)
10 (100)
Pos
36 (62)
28 (72)
0 (0)
CONSTRAINTS OF PCR
TECHNIQUE
1. Quite expensive
2. Need special equipment
3. Need high skill and laboratory
4. Sophisticated
Mochammad Hatta@2013
Salmonella
bacteria on
MacConkey
agar
Lactosepositive
bacteria show
pink colonies
(upper left)
Lactosenegative
bacteria have
colorless
colonies (lower
right)
Mochammad Hatta@2013
Mochammad Hatta@2013
Black
colonies of
Salmonell
a typhi
after
growth on
bismuth
sulfite
agar
Mochammad Hatta@2013
Mochammad Hatta@2013
Patients with
clinical
suspicion of
typhoid fever
from Makassar,
Indonesia
Mochammad Hatta@2013
Control
Test
Sensitivity (%)
Specificity (%)
75
68
52
94
92
95
Widal O 1:400
Widal H 1:200
47
60
93
98
Dipstick
77
95
Mochammad Hatta@2013
Patient group,
culture result
S. typhi positive
S. typhi negative
38 (70.4) / 54
0 (0) / 2
3 district hospitals
(blood culture)
S. typhi positive
S. typhi negative
32 (86.5) / 37
2 (7.7) / 26
Mochammad Hatta@2013
No. positive (% ) /
total
Suspects
Clinical diagnosis: typhoid
S. typhi culture positive
S. paratyphi culture positive
Culture negative
Clinical diagnosis: other
Culture negative
Hospital controls
School children
85 (47.5) / 179
73 (65.2) / 112
4 (66.6) / 6
8 (13.1) / 61
0 (0) / 64
0 (0) / 259
2 (1) / 194
Mochammad Hatta@2013
DPO
No. positive (% ) /
Total
8
15
29
30 (76.9) / 39
32 (82.1) / 39
38 (97.4) / 39
6
13
27
2 (4.3) / 47
36 (76.6) / 47
39 (83.0) / 47
Sample
Mochammad Hatta@2013
Typhoid fever
Culture and Dipstick
Assay
Sensitivity Specificity
PPV
NPV
Culture
65.9%
100%
100%
74%
Dipstick
47.5%
95%
92%
65%
Mochammad Hatta@2013
culture
PPV (92%) and NPV (64%) somewhat
lower than that of culture
Same day result
Easy to perform
High stability of components
Mochammad Hatta@2013
Mochammad Hatta@2013
Sample pad /
blood cell
separation filter
Conjugate
pad
Control
Detection strip
Mochammad Hatta@2013
Sink
Add 5l serum
Add 130l sample fluid
Wait 10 minutes
Control line
Read result
Test line
Sample well
5 seconds
45 seconds
15 seconds
> 60 seconds
Mochammad Hatta@2013
TREATMENT
Medical care include rehydration, antipyretics &
antibiotics.
Drugs of choice are Ceftriaxone & ciprofloxacin
but Cotrimoxazole & Chloramphenicol are still
used in developing countries. Ampicillin kills
bacilli hiding in the bile & hence prevents or
reduce the carrier state.
Chronic resistant carrier state may necessitate
cholecystectomy. Surgical care may also be
needed in patients with intestinal complications.
Mochammad Hatta@2013
NURSING CARE
Isolation & barrier nursing is indicated
Notification of the case to the infection control
nurse in the hospital.
Trace source of infection.
continue breastfeeding infants & young children
and give ORS & light diet for other patients in the
first 48 hours.
Mochammad Hatta@2013
PREVENTION
Education on hygiene practices like hand
washing after toilet use & avoidance of eating in
non hygienic restaurants.
Proper handling & refrigeration of food even
after cooking.
Salmonella TAB vaccine is available but
affectivity is low (50% claimed protection).
Antibiotic prophylaxis is not needed for
house-hold contacts.
Mochammad Hatta@2013
PROGNOSIS
With early diagnosis and prompt treatment
most patients with typhoid fever will recover in
due time.
Fever & toxicity subsides within 72 hours of
antibiotic treatment.
Mortality is > 50% in untreated severe typhoid
fever particularly in children & elderly.
Recrudescence is rare but chronic carrier
state is reported in 10% of patients.
Mochammad Hatta@2013
TRANSMISSION
Infection follows ingestion of contaminated
food or water. Meat, poultry, eggs & diary
products are frequent sources.
Pets, domestic animals and infected human
are potential reservoirs. Person to person &
animal to human transmission is recognized.
In healthy humans a dose of about one million
bacteria is necessary to produce symptoms.
Mochammad Hatta@2013
References
Mochammad Hatta, Mirjam Baker, Stella van Beer, Theresia H Abdoel, Henk L Smits. Risk
factors for clnical typhoid fever in villages in Rural South Sulawesi, Indonesia. International
Journal of Tropical Medicine. Vol 4 (3): 91-99, (2009)
Mochammad Hatta and Ratnawati. Enteric fever in endemic areas of Indonesia: an
increasing problem of resistance. J. Infection Developing Countries (JIDC). Vol 2(4); 298301 (2008)
Rob Pastoor, Mochammad Hatta, Theresia H. Abdoel, Henk L. Smits. Simple, rapid and
affordable point-of-care test for the serodiagnosis of typhoid fever. J. Diagnostic
Microbiology and Infectious Disease. Vol 61:(2);129-134, Feb (2008).
Mochammad Hatta and Henk L Smits. Detection of Salmonella typhi by nested Polymerase
Chain Reaction in blood, urine and stool samples. American J. Tropical Medicine
Hygiene.vol : 76;139-143 (2007).
Theresia H. Abdoel, Rob Pastoor, Henk L. Smits, Mochammad Hatta, Laboratory evaluation
of a simple and rapid latex agglutination assay for the serodiagnosis of typhoid fever .
Transactions of the Royal Society of Tropical Medicine and Hygiene . vol. 101 (10);
1032-1038 (2007)
Mochammad Hatta, Marga D.A Goris, Evy Heerkens, George C Gussenhoven, Jairo Goosken,
Henk L Smits. Simple dipstick assay for the detection of Salmonellla typhi-specific
immunoglobulin M antibodies and the evolution of the immune response in patients with
typhoid fever American J. Tropical Medicine and Hygiene . vol 66: no 4; 416-421 (2002).
Mochammad Hatta, Mubin Halim, Theresia Abdoel, Henk L. Smits. Antibody response in
typhoid fever in endemic Indonesia and relevance of serology and culture to diagnosis.
Southeast Asian Journal of Tropical Medicine and Public Health . vol 33: no 4; 182-191
(2002).
Mochammad Hatta@2013