Practical Session

Evidence Based Medicine

Block B6

Subgroup: Diagnosis

- Abdur Rohman (18811)

- Firda Rezkia Utari (18840)
- Niko Putra Dewata (19107)
- Rajwa Naajiyah (19125)
- Ratna Puspitasari (19126)
 1. Clinical Scenario
TYPHOID FEVER

Scenario 1
A 32 years old male visited your clinic with complaint feeling weak, cold
and tired . He also had headache, backache, diarrhea, constipation, loss of
appetite. The body temperature rises and remains high for about 10-14
days. Body temperature typically rises in the evening and drops in the
morning. You took blood sample and did a laboratory test to detect the
presence of IgM antibodies to the S. Typhi antigen (TYPHDOT) and the
result of the test was positive. What is probability that he really suffer
from the typhoid fever?
 2. Clinical Question

Possible question:

“In patient with fever, does Typhidot diagnostic kits

compared with blood culture, diagnose typhoid fever?”
 3. PICO
Question Part Question Term
Population/patient Patient with fever
Intervention Typhidot
Comparison Blood Culture
Outcome Diagnosis of Typhoid Fever
 4. Searching Methods
 Keywords for searching
• Typhoid Fever OR Enteric Fever
• Typhidot OR IgM/IgG
• Blood Culture OR Blood Smear
• [Typhoid Fever OR Enteric Fever] AND [Typhidot OR IgM/IgG] AND [Blood
Culture OR Blood Smear]
 Searching websites
• https://www.ncbi.nlm.nih.gov/pubmed
 Selection criteria for the evidence/article
• Year Published > 2010
• NOT meta-analysis or systematic review
• English only
• Developing countries
• Free full text article
 4. Searching Methods
 Searching flow

Exclusion based Exclusion based Exclusion based

• Typhidot on free article • Exclude: n=7 on tittle • Exclude: n=2 on abstract
• n = 34 • Exclude: n = 12 • Incude: n =15 • Exclude: n=4 • Include: n=9 • Exclude: n=2
• Include: n = 22 • Incude: n =11 • Include: n=7

Searches in Exclusion based Exclusion based

PubMed on year on type
 5. Results of Critical Appraisal
The Article
No. Title
1 Typhidot M and Diazo test vis-a-vis blood culture and Widal test in the early diagnosis
of thypoid fever in children in a resource poor setting
2 A comparative study of the typhidot (Dot-EIA) and Widal tests in blood culture
positive cases of thypoid fever
3 Comparative Evaluation of Various Tests for Diagnosis of Concurent Malaria and
Typhoid Fever in a Tertiaty Care Hospital of Northern India
4 Comparative Evaluation of Tubex TF (Inhibition Magnetic Binding Immunoassay) for
Thypoid Fever in Endemic Area
5 Typhidot - A blessing or a menace
 5. Results of Critical Appraisal
Step 1 : Are the results of the study valid?
Question 1 2 3 4 5

Was the diagnostic test evaluated in a Representative

spectrum of patients (like those in whom it would be NO YES YES YES YES
used in practice)?
Was the reference standard applied regardless of the
YES YES NO YES YES
index test result?
Was there an independent, blind comparison between
UN- UN- UN- UN- UN-
the index test and an appropriate reference (‘gold’) CLEAR CLEAR CLEAR CLEAR CLEAR
standard of diagnosis?
 5. Results of Critical Appraisal
Step 2 : What were the results?
Are the test characteristics presented? 1 2 3 4 5
Sensitivity (Sn) 90% 97.37% 100% 72% 26.67%

Specificity (Sp) 38.26% 95.83% 95.21% 92.67% 61.54%

Positive Predictive Value ( PPV) 27.55% 97.37% 13.63% 76.59% 7.4%

Negative Predictive Value (NPV) 93.62% 95.83% 100% 90.85% 87.91%
 5. Results of Critical Appraisal
Step 3 : Applicability of the results?

Were the methods for performing the test described

1 2 3 4 5
in sufficient detail to permit replication?

YES √ √ √ √

NO √

UNCLEAR
 6. Table of Evidence/Article
Study Title Typhidot M and Diazo test vis-à-vis blood culture and Widal test in the early diagnosis of typhoid fever
in children in a resource poor setting
Authors Farzana K Beig, Faraz Ahmad, Mohd Ekram, Indu Shukla
Study Objective Evaluate typhidot M and Diazo tests vis-à-vis blood culture and Widal test in children
Study Design Prospective study
Study Participants Patients aged 6 months to 12 years, having fever of more than four days duration with clinical suspicion
of typhoid fever were enrolled. Patients in whom other diagnosis was made served as control.
Number of Subjects 145 clinically suspected enteric fever cases.
Study Settings The study was conducted in the department of pediatrics Jawahar Lal NehruMedical College Hospital, a
tertiary care hospital in the northern part of India.
Intervention Typhidot test, Diazo test, Widal test, Blood culture
Study Results Blood culture was positive in only 27.3% of the cases. Among these culture positive cases, typhidot M
test had the highest sensitivity, specificity, PPV and NPV. Diazo test ranked next. Among clinically
suspected typhoid cases, the overall sensitivity, of blood culture, Widal, typhidot M, Diazo was 27.3%
(95% CI = 19.8- 36.3), 64.6% (95% CI = 55.3-72.9), 89.1% (95% CI = 81.9-93.7), 80.9% (95% CI = 72.6-87.2)
respectively. In the first week of illness, typhidot M showed the best sensitivity [86.2% (95% CI = 69.4-
94.5)] followed by Diazo, Widal, and blood culture.
Study Conclusion Both Typhidot M and Diazo are good screening tests for the diagnosis of typhoid fever. Typhidot M is
superior to Diazo but the latter is more suitable to resource poor settings being economic and easy to
 6. Table of Evidence/Article
Study Title A comparative study of the typhidot (Dot-EIA) and Widal tests in blood culture positive cases of typhoid fever
Authors Haji Khan Khoharo
Study Objective Evaluate the sensitivity and specificity of typhidot in terms of diagnostic yields compared to the Widal test
Study Design Comparative case control
Study Participants The subjects were selected from those who satisfied the following criteria: aged 18–40 years; fever 14 days; clinical
manifestations suggestive of typhoid fever; no history of antibiotic therapy and typhoid immunization in the recent
past.
Number of Subjects Blood culture positive typhoid cases 76 patients and a control sample of 48 patients with non-typhoid febrile illness.
Study Settings Department of Medicine, Muhammad Medical College Hospital, Mirpukhas, Sindh, Pakistan, April 2008 to August 2009.
Intervention Typhidot test, Widal test, Blood culture
Study Results The typhidot test was positive in 74 (97.36%) cases, with a sensitivity, specificity and positive predictive value of 96%,
89.5%, and 95%, respectively, compared to theWidal test which was positive in 56 (73.68%) cases with a sensitivity,
specificity, and positive predictive value of 72%, 87%, and 87%, respectively (P ¼ 0.001). In the control group, seven
(14.5%) cases tested positive for the Widal test and two (4.16%) for the typhidot (P ¼ 0.001), yielding the sensitivity and
specificity for the Widal test and the typhidot test of 63% and 83%, and 85% and 97%, respectively
Study Conclusion the Dot-EIA (enzyme immunoassay; typhidot) is amore sensitive and specific test which is easy to performand more
reliable compared to theWidal test and that it is useful in early therapy.
 6. Table of Evidence/Article
Study Title Comparative Evaluation of Various Tests for Diagnosis of Concurrent Malaria and Typhoid Fever in a Tertiary Care
Hospital of Northern India
Authors Deepika Verma, Sachin Kishore, M.E. Siddique
Study Objective Diagnosis and comparative evaluation of various tests for diagnosis of Typhoid-Malaria co-infection in patients
suffering from febrile illness.
Study Design Prospective study
Study Participants A total of 800 blood samples were collected (5ml of blood drawn by venepuncture) from consecutive febrile patients,
both OPD and IPD,
Number of Subjects 800 Patients
Study Settings Dept of Microbiology, Rohilkhand medical college and Hospital, Bareilly, U.P, India, during July-Sept 2012.
Intervention Typhidot test, Widal test, blood culture, stool culture
Study Results 68 (8.5%) patients were found to be suffering from co- infection by the above tests. Blood culture revealed 15 (22%)
bacterial pathogens in the widal positive patients out of which 6 (8.8%) were Salmonella Typhi and 3 (4.41%) were
Salmonella Paratyphi A. Stool culture revealed 8 (11.7%) S. Typhi and 5 (7.35%) S. Paratyphi A cases.
Study Conclusion History of prior antibiotic intake, previous infection and vaccination are important before interpreting results of
widal test and combining culture with typhidot M will significantly help in diagnosis of typhoid fever especially in
patients who had previously taken antibiotics
 6. Table of Evidence/Article
Study Title Comparative Evaluation of Tubex Tf (Inhibition Magnetic Binding Immunoassay) for Typhoid Fever in
Endemic Area
Authors Ashish Khanna, Menka Khanna, Karamjit Singh Gill
Study Objective Compare the sensitivity and specificity of widal test, typhidot and tubex TF test for the diagnosis of
typhoid fever in an endemic country like India.
Study Design Cross-sectional study
Study Participants 50 patients of typhoid fever, 50 patients of non typhoid fever and 100 normal healthy individuals
Number of Subjects 50 patients of typhoid fever, 50 patients of non typhoid fever and 100 normal healthy individuals
Study Settings Department of Microbiology, Sri Guru Ram Das Institute of Medical Sciences and Research, Amritsar,
during the six month period from March 2014 to August 2014.
Intervention Widal test, Typhidot test, Tubex TF Test, Blood culture
Study Results Typhidot (IgM or IgG) was positive in 72% of typhoid fever patients and 10% and 6% in non typhoid
fever and normal healthy individuals respectively.
Study Conclusion The study showed better results with the Tubex TF test as compared with widal test/typhidot test.
These results should be further confirmed by large cross sectional studies in other endemic areas.
 6. Table of Evidence/Article
Study Title Typhidot - A blessing or a menace
Authors Khalid Mehmood, Ayesha Sundus, Iftikhar Haider Naqvi, Mohammad Faisal Ibrahim, Osama Siddique, Nida Faisal
Ibrahim
Study Objective Evaluate the sensitivity and specificity of Typhidot in patients with fever
Study Design Retrospective analysis
Study Participants Patient presented with a history of fever of at least 3 days, whatever their ultimate diagnosis might have been
Number of Subjects 145 febrile patients
Study Settings Civil Hospital Karachi affiliated with Dow University of Health Science and Anklesaria Nursing Home Karachi, Pakistan
Intervention Typhidot and Blood Culture
Study Results Out of 145 patients, 15(10.3%) had positive blood culture for Salmonella typhi, 7 (4.8%) had positive culture for
salmonella paratyphi and 94(64.8%) had positive culture for other organisms. Twenty nine (20%) patients had
negative culture results. Forty seven (32.4%) patients had only IgM positive on Typhidot, 7(4.8%) had both IgM and
IgG positive and 91(62.8%) had both IgM and IgG negative. Amongst the 130 patients with diseases other than
typhoid, 50(38.5%) showed a positive Typhidot result. Amongst the 15 patients with typhoid, 11(73.3%) showed a
negative Typhidot result.
Study Conclusion Even though Typhidot is rapid, easy and affordable, its use should be discouraged due to low sensitivity and specificity
and insignificant (p=0.067) association to the disease
7. Answer The Clinical Question
 8. Reference List
Farzana K. Beig, Faraz Ahmad, Mohd Ekram, Indu Shukla. Typhidot M and Diazo test vis-à-vis blood
culture and Widal test in the early diagnosis of typhoid fever in children in a resource poor
setting. The Brazilian Journal of Infectious Diseases 2010;14(6):589-593. doi:
https://doi.org/10.1016/S1413-8670(10)70116-1
Khanna A, Khanna M, Gill KS. Comparative Evaluation of Tubex Tf (Inhibition Magnetic Binding
Immunoassay) for Typhoid Fever in Endemic Area. 2015;9(11):DC14-DC17. doi:
https://doi.org/10.7860/JCDR/2015/15459.6810
Khoharo, Haji Khan. A comparative study of the typhidot (Dot-EIA) and Widal tests in blood culture
positive cases of typhoid fever. Tropical Doctor 2011;41(3):136-138. doi:
https://doi.org/10.1258/td.2011.100406
Mehmood K, Sundus A, Naqvi IH, Ibrahim MF, Siddique O, Ibrahim NF. Typhidot - A blessing or a
menace. Pak J Med Sci 2015;31(2):439-443. doi: http://dx.doi.org/10.12669/pjms.312.5934
Verma, Deepika & Kishore, Sachin & Siddique, M.E. Comparative Evaluation of Various Tests for
Diagnosis of Concurrent Malaria and Typhoid Fever in a Tertiary Care Hospital of Northern India.
Journal of clinical and diagnostic research 2014;8(6):DC41-DC44. doi:
https://doi.org/10.7860/JCDR/2014/7745.4403
THANK YOU

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