TUBEX® TF Rapid typhoid detection

Confidence in typhoid fever diagnosis

TUBEX® TF is a rapid in vitro diagnostic test for detection of typhoid fever, a disease caused by
Salmonella typhi. It enables diagnosis of acute phase disease by detection of infection-specific
S. typhi anti-O9 IgM antibodies in patient serum. TUBEX® TF is based on a new technology;
IMBI™ - Inhibition Magnetic Binding Immunoassay - a semi-quantitative colorimetric assay,
completed within 10 minutes. A positive TUBEX® TF result, together with typical clinical
symptoms, is a strong indication of acute typhoid fever.

IMBI™ assay for infection-specific antibody detection.

IMBI™ is a semi-quantitative assay technology, utilizing the
antigen-coated
magnetic detector advantages from the traditional Widal technique, being simple
particle and based on visual interpretation of fluid; combined with
specificity normally accorded to ELISAs, using purified antigens
for detection.
antibody-coated
colored indicator
particle The IMBI™ technology allows for detection of infection-specific
antibodies in patient serum by assessing their ability to inhibit
the reaction between the detector antigen, coated on magnetic
particles, and the indicator antibody, coated on colored latex
particles.
The efficiency of the IMBI™ reaction is further made possible
by specifically designed reaction wells. The reaction is sepa-
rated using magnetic force. The color of the supernatant is
patient´s infection-
specific antibody
proportional to the concentration of infection-specific antibo-
dies found in patient serum. Scoring of results are performed
by visual interpretation.

TUBEX® TF test principle. Example of negative test TUBEX® TF combines the antigen S. typhi LPS as detector with
result (upper) and positive test result (lower). a specific monoclonal antibody directed against the S. typhi O9
Modified after Lim et al J Clin Microbiol 1998. antigen as indicator.

Assay procedure. TUBEX® TF is completed in a few steps as illustrated below.

1 TUBEX® TF 2 Sample or 3 Incubate 2 min. 1. Add 45µl TUBEX® TF Brown Reagent (detector) to the
Brown Reagent TUBEX® TF TUBEX® Reaction Well Strip.
(45µl). Control (45µl).
Mix 10x. 2. Add 45µl patient sample, TUBEX® TF Positive Control or
TUBEX® TF Negative Control. Mix 10 times by pipetting.

3. Incubate on the bench for 2 minutes.

4. Add 90µl TUBEX® TF Blue Reagent (indicator).

5. Cover the TUBEX® Reaction Well Strip using the TUBEX®

4 TUBEX® TF 5 Cover strip 6 Separate 5 min on Sealing Tape. Tilt and shake the TUBEX® Reaction Well Strip
Blue Reagent Shake 2 min. TUBEX® Color Scale for 2 minutes.
(90µl). Read results.
6. Place the TUBEX® Reaction Well Strip on the TUBEX® Color
Scale. Allow separation for 5 minutes. Read and score the
results by comparing the color of each supernatant to the
TUBEX® Color Scale. The color scale range from 0 (negative
Color Scale
test; clear pink) to 10 (positive test; intense blue)

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TUBEX® TF Rapid typhoid detection

Typhoid fever diagnosis. A clinical symptom of typhoid fever is high body temperature, a symptom applicable
to a number of infectious diseases. For use in endemic areas, a test needs to be specific, easily accessible and
having a short turnaround time. TUBEX® TF fulfills these criteria, being a rapid, stand-alone test for detection of
current typhoid fever by its specific IgM detection.

The awareness of the clinical benefits of TUBEX® TF in endemic settings is increasing. A few examples on clinical
trials forming the basis for this are presented below.
In a comparative trial in the Philippines, Kawano and co-workers found TUBEX® TF to be 95% sensitive at 80%
specificity (75 culture-proven S. typhi infected patients, and 102 culture-negative non-typhoidal patients; see below).
Being an IgM test, earlier detection of current disease
compared to culture positivity is commonly seen. Thus,
Sensitivity Specificity PPV NPV
(%) (%) (%) (%) considering 14 TUBEX® TF positive, culture-negative
TUBEX TF
®
95 80 78 95 cases as true positives, the TUBEX® TF specificity is
increased to 93%. The positive predictive value was
SD Bioline lgM 69 79 68 80
78%, and the negative predictive value was 95%. In
SD Bioline lgG 71 76 65 80 this comparative trial, TUBEX® TF was stated to score
Typhidot lgM 55 65 53 66
best among the assays analyzed. It fulfilled the required
criteria for a serological test to be useful in a routine
Typhidot lgG 73 46 50 70 setting and to be a solid alternative to blood culture.
Mega lgM 91 49 57 88
In a Vietnamese prospective trial, another 59 culture-
Mega lgG 96 39 54 93
proven S. typhi infected patients and 20 controls were
Modified after Kawano et al J Clin Microbiol 2007. included by Olsen and co-workers. A vast majority
had taken antibiotics prior to visit, a factor known to
negatively affect outcome of culture. Here, Widal sho-
8
wed 64% sensitivity at 76% specificity, as compared to
6
TUBEX® TF showing 78% sensitivity at 94% specificity.
4
Frequency distribution of According to the authors, TUBEX® TF demonstrated
N:o of samples

2 serum samples obtained promising results and was further the easiest test to
0 from typhoid fever-proven
60 and typhoid-suspected use among the various assays analyzed.
patients (upper), and
40 control subjects (lower) In a prospective trial in Bangladesh by Rahman and
20
according to their TUBEX® co-workers, a total of 243 febrile outpatients (mainly
TF scores.
0
children and adolescents) and 57 healthy controls were
0 1 2 3 4 5 6 7 8 9 10 enrolled. Based on culture results, TUBEX® TF was
TUBEX® TF score 91% sensitive and 82% specific in febrile subjects.
Specificity increased to 90% in nonfebrile, healthy sub-
Modified after Lim et al J Clin Microbiol 1998.
jects, suggesting that some culture-negative patients
were truly typhoidal. For Widal, the corresponding
Assay IMBI™ (Inhibition Magnetic Binding Immunoassay)
figures were 82% sensitivity at 58% specificity.
Antigen S. typhi LPS O9 (α-D-tyvelose)
References
Detection S. typhi IgM O9-antibodies
Kawano RL et al. Comparison of serological test kits for diagnosis of typhoid fever in
Samples serum
the Philippines. J Clin Microbiol 2007; 45: 246-247.
Analytical sensitivity 15 – 20 µg/ml
Lim PL et al. One-step 2-minute test to detect typhoid-specific antibodies based on
Procedure < 10 minutes particle separation in tubes. J Clin Microbiol 1998; 36: 2271-2278.
Results visual semi-quantitative scoring (0 – 10) Olsen SJ et al. Evaluation of rapid diagnostic tests for typhoid fever. J Clin Microbiol
scores ≥ 4 positive 2004; 42: 1885-1889.
Reproducibility > 90% Rahman M et al. Rapid detection of early typhoid fever in endemic community child-
Sensitivity 80 – 95% ren by the TUBEX O9-antibody test. Diagn Microbiol Infect Dis 2007; 58: 275-281.
Specificity 80 – 95% Tam FCH et al. The TUBEX typhoid test based on particle-inhibition immunoassay
detects IgM but not IgG anti-O9 antibodies. J Imm Meth 2003; 282: 83-91.
TUBEX® is a registered trademark of IDL Biotech AB. WHO. Background document: The diagnosis, treatment and prevention of typhoid
IMBI™ is a trademark of IDL Biotech AB. fever. 2003; 11-16. WHO/V&B/03.07 (www.who.int/vaccines-documents/)
May 2008/91-602-01/ © IDL Biotech AB

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