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Typhoid Fever

Diagnosis
Blood and bone marrow culture

The definitive diagnosis of typhoid is by the isolation of

the organism from a sterile site
In untreated patients, blood cultures are usually positive
in about 6080% of cases, usually early in the course of
disease. The number of viable organisms/mL is low, a
median of 1 bacteria per mL of blood, so at least 510 mL
of blood should be taken to increase the sensitivity of
blood culture.
A success rate of about 8090% is obtained from bone
marrow culture, where the viable bacterial load becomes
higher as disease progresses.
Prior antibiotic therapy makes positive blood culture less
likely but the bone marrow culture often remains positive
in the face of antibiotic therapy.
A high yield (60%) has also been reported from rose-spot
cultures in such a situation.
Bone marrow aspiration and blood are cultured in a
selective medium (eg, 10% aqueous oxgall) or a nutritious
medium (eg, tryptic soy broth) and are incubated at 37C
for at least 7 days. Subcultures are made daily to one
selective medium (eg, MacConkey agar) and one
inhibitory
medium
(eg, Salmonella-Shigella agar).
Identification of the organism with these conventional
culture techniques usually takes 48-72 hours from
acquisition.

Faecal and urine cultures

With modern techniques, faecal cultures are often positive

even during the first week, though the percentage
positivity rises steadily thereafter. Later in the illness,
stool culture results are positive because of bacteria shed
through the gallbladder.
Urine cultures are positive less often.
Cultures of punch-biopsy samples of rose spots reportedly
yield a sensitivity of 63% and may show positive results
even after administration of antibiotics.
A single rectal swab culture upon hospital admission can
be expected to detect S typhi in 30%-40% of patients.
S typhi has also been isolated from the cerebrospinal fluid,
peritoneal fluid, mesenteric lymph nodes, resected
intestine, pharynx, tonsils, abscess, and bone, among
others.

Table 2. Sensitivities of Cultures

Week 1

Week 2

Week 3

Week 4

Incubation
Bone marrow aspirate (0.5-1
mL)
Blood (10-30 mL), stool, or
duodenal aspirate culture

Urine

90% (may decrease after 5 d of

antibiotics)
40%-80%

~20%

Variable
(20%60%)

25%-30%, timing unpredictable

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Serology

The traditional Widal test measures antibodies against

flagellar (H) and somatic (O) antigens of the causative
organism. In acute infection, O antibody appears first,
rising progressively, later falling and often disappearing
within a few months.
H antibody appears a little later but persists for longer.
Rising or high O antibody titre generally indicates acute
infection, whereas raised H antibody helps to identify the
type of enteric fever.
However, the Widal test has many limitations. Raised
antibodies may have resulted from previous typhoid
immunization or earlier infection(s) with salmonellae
sharing common O antigens with S. Typhi or S. Paratyphi.
In endemic countries, patients have higher H antibody
titres. This is a particular problem in developing countries,
where background antibodies mean that the Widal test
lacks sensitivity.
Indirect
hemagglutination,
indirect
fluorescent
Vi
antibody, and indirect enzyme-linked immunosorbent
assay (ELISA) for immunoglobulin M (IgM) and IgG
antibodies to S typhi polysaccharide, as well as
monoclonal antibodies against S typhi flagellin, are
promising, but the success rates of these assays vary
greatly in the literature.

Newer tests that directly detect IgM or IgG antibodies to a

wide range of specific S. typhi antigens have been
developed, such as Typhidot and Tubex. Some of these
tests have been adapted to a simple dipstick technique
using whole bacteria antigens to detect IgM antibody and
may be of benefit in situations where a laboratory is not
available.
Their use should currently be confined to outbreak
situations, where pretest probability of typhoid is high.
Urinary Vi antigen ELISAs and PCR-based assays are under
development, but have not yet reached the point where
they are ready for deployment as rapid-diagnostic tests.

Differential Diagnosis

Abdominal Abscess
Amebic Hepatic Abscesses
Appendicitis
Brucellosis
Dengue Fever
Influenza
Leishmaniasis
Malaria
Rickettsial diseases
Toxoplasmosis
Tuberculosis
Tularemia
Typhus

Newer diagnostic methods

Dila Larasati
130110110173 | B3

References:
Mansons Tropical Diseases, 23rd Edition
http://emedicine.medscape.com/article/231135