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Comparative study of

Typhidot-M with Widal and


blood culture in diagnosis of
enteric fever
Group 7

Guston, Gutierrez, Hizon, Lansang, Limos


WIDAL TEST
The Widal test is a blood test, widely used for serological diagnosis of enteric
fever. It measures the specific antibody titre of the patient's serum against
salmonella antigens by hemagglutination.

Increased O antigen signifies acute infection

Increased H antigen may indicate the serotype of the infecting organism or


an early infection.
Typhidot M test
Typhidot is a dot blot enzyme-linked immunosorbent assay (ELISA) which
detects IgM and IgG antibodies.

Detection of IgM reveals the early phase of the disease

Detection of IgM and IgG suggests a middle phase of the disease

Typhidot M test in which inactivation of IgG, allows access to the IgM and
hence it is more specific.
Methodology
Inclusion and Exclusion
INCLUSION CRITERIA EXCLUSION CRITERIA

Children in the age group of 1-18 years Children with identified cause of fever:
admitted to ESIC MC and PGIMSR, respiratory illness,
Department of Pediatrics malaria,
With fever of 5 days with signs and symptoms diarrhea, and
suggestive of typhoid fever: urinary tract infection and
anorexia, children with
vomiting, documented typhoid fever within the
diarrhea, past 8 weeks
toxicity,
abdominal pain,
constipation,
headache,
jaundice,
obtundation, and
hepatosplenomegaly

Comparative study of Typhidot-M with Widal and blood culture in diagnosis of enteric fever, Udayakumar et al., pg 65
Results and
Discussion
Results (Incidence)

AGE GROUP INCIDENCE (%)

1-5 y/o 31 (11.85%)


6-10 y/o 98 (46%)
11-18 y/o 141 (52.2%)

Male to Female Ratio: 1.3:1 (152:118)

Comparative study of Typhidot-M with Widal and blood culture in diagnosis of enteric fever, Udayakumar et al., pg 65
Discussion
In the present study, most of the children were in the age group of 5-18 years.
The lower incidence in pre-school children is in concordance with studies from
South America and other parts of the world which suggest that typhoid may
manifest as a mild illness in young children. However, there is emerging
evidence from high incidence study sites such as South Asia that the incidence
of EF in pre-school children aged 2-5 years is in the same order of magnitude
as that of schoolaged children (5-15 years) with higher rates of complications
and hospitalization .

Comparative study of Typhidot-M with Widal and blood culture in diagnosis of enteric fever, Udayakumar et al., pg 65-66
Results

Comparative study of Typhidot-M with Widal and blood culture in diagnosis of enteric fever, Udayakumar et al., pg 66
Results

Comparative study of Typhidot-M with Widal and blood culture in diagnosis of enteric fever, Udayakumar et al., pg 66
Results (Diagnostic Tools)

Diagnostic Tool Positive Results

Widal Test 107 (39.6%)


Typhidot-M 136 (50.4%)
Blood Culture 82 (30.4%)

Comparative study of Typhidot-M with Widal and blood culture in diagnosis of enteric fever, Udayakumar et al., pg 66
Discussion
In the study, culture positivity among clinically suspected case was 30.4%.

In other studies, the culture positivity varied from 6% to 68% , and in


majority of the studies, the culture yield was around 40% .

The major reason for this lower yield is widespread use of antibiotics in the endemic
areas and the small quantities of salmonella typhi (i.e., <15 organisms/ml) typically
present in blood

Although blood culture is the gold standard test for diagnosis of EF,
its utility in early diagnosis is limited due to lower yield, requirement of
trained personnel, and the time period (2-3 days) required for reporting.
Discussion
Sensitivity Speciificity PPV

Present Study 78% 79.3% 59.8%


Sherwal et al. 74% 83% 87.5%
Rahman et al. 81.8% 69.2% 45.6%

Sharing of O & H antigen by other Salmonella serotypes and other members of


Enterobacteriaceae makes the role of Widal test less specific, and hence, its use is
controversial in diagnosis of EF. I

It is possible that the Widal test would have performed better if paired sera were tested
to demonstrate the rising titers. Patients rarely return for outpatient follow-up once
treated so that obtaining paired sera in a routine clinical setting is unlikely, and hence
clinicians widely rely on positive Widal test done on a single serum sample.
Both Widal and Typhidot-M appear to correlate less satisfactorily with blood culture as
among children with positive blood cultures, Typhidot-M was negative in 15 (28%) and
Widal was negative in 18 (22%) children. Although both these tests, at best, can be used
to suspect EF more strongly than on clinical grounds alone, it is prudent to follow them
up with blood culture confirmation. With this caveat, Typhidot-M appears to have
slight advantage over Widal test in that

(i) results are rapidly available,

(ii) there is possibility of using it earlier (1st week) in the course of the illness, and

(iii) it is technically easy to perform even at the peripheral health-care facilities.


Discussion
Limitations of the study was that it was a single-center study with relatively
lower rate of culture positivity in the study group.
Conclusion
Critical
Appraisal
Critical Appraisal
1. Was there an independent blind comparison with the reference?

No, the study did not mention any method of blinding within the study,
which is then assumed to be an open-label type of study. However, the
researchers used a reference or gold standard to determine accurately the
presence or absence of the disease
Critical Appraisal
1. Was there an independent blind comparison with the reference?

Comparative study of Typhidot-M with Widal and blood culture in diagnosis of enteric fever, Udayakumar et al., pg 65
Critical Appraisal
2. Did the patient sample include an appropriate sample to include a
spectrum of patients to whom the diagnostic test will be applied in clinical
practice?

Comparative study of Typhidot-M with Widal and blood culture in diagnosis of enteric fever, Udayakumar et al., pg 65
Critical Appraisal
2. Did the patient sample include an appropriate sample to include a
spectrum of patients to whom the diagnostic test will be applied in clinical
practice?

Comparative study of Typhidot-M with Widal and blood culture in diagnosis of enteric fever, Udayakumar et al., pg 65
Critical Appraisal
2. Did the patient sample include an appropriate sample to include a
spectrum of patients to whom the diagnostic test will be applied in clinical
practice?

Partial Yes and Partial No. Based on the inclusion and exclusion criteria
they were able to screen the patients in clinical practice based on the
presenting signs and symptoms. However, they were not able to differentiate
within the spectrum of disease with regards to low, moderate and high clinical
suspicion. Additionally, the researchers were not able to further discuss or
analyze their patients characteristics. The only available data present is the
incidence of the presence of Salmonella Typhi by age group

Comparative study of Typhidot-M with Widal and blood culture in diagnosis of enteric fever, Udayakumar et al., pg 65
Critical Appraisal
3. Did the result of the test being evaluated influence the decision to perform
the reference standard?

Comparative study of Typhidot-M with Widal and blood culture in diagnosis of enteric fever, Udayakumar et al., pg 65
Appraisal
3. Did the result of the test being evaluated influence the decision to perform
the reference standard?
Critical Appraisal
3. Did the result of the test being evaluated influence the decision to perform
the reference standard?

No. The researchers designed their methodology to perform the


reference standard of blood culture with Typhidot-M and Widal Test
simultaneously.
Critical Appraisal
4. Where the methods for performing the test described in sufficient detail to
permit replication?

No. The researchers opted to only include the methodology of the


Typhidot-M test. They did elaborate on the methodology of the reference
standard and Widal Test.
Critical Appraisal
5. Are the likelihood ratio for the test results presented or data for their
calculation provided?
Critical Appraisal
6. Will the reproducibility of the test result and its interpretation be stisfactory
in my setting?
Critical Appraisal
7. Are the results applicable to my patients?
Critical Appraisal
8. Will the result change my management?

Yes, because based from the results of the study was found to be useful
alternative to Widal Test as it is more specific and useful in early diagnosis of
enteric fever (EF). It is rapid and easy to perform, requiring less than 30 mins.

It is still avisable to to confirm the diagnosis with blood culture, especially


with well documented presence of multidrug resistant strains of Salmonella
typhi worldwide.

Comparative study of Typhidot-M with Widal and blood culture in diagnosis of enteric fever, Udayakumar et al., pg 66.
Discussion, 5th Paragraph ; pg 67, Conclusion
Critical Appraisal
9. Will the patients be better of with the results of the test?

Yes, a fast, reliable and easy to perform serodiagnostic test with a higher
sensitivity and specificity than Widal test is required for rapid diagnosis and
management of typhoid cases, thereby enabling clinicians to initiate an early
therapy, reducing morbidity and its complications.
Computations
Typhoid Fever

Disease Disease
Present Absent

Test Positive 64 39

WIDAL TEST
Test Negative 18 149
Disease Disease Total
Present Absent
Test Positive 64 39 103
WIDAL Test Negative 18 149 167
TEST
Total 82 188 270

Sensitivity Positive Predictive Value


= 64/82 = 64/103
=0.78 =0.621
=78% =62.1%

Specificity Negative Predictive Value


= 149/188 = 149/167
=0.793 =0.892
=79.3% =89.2
Likelihood Ratio +
= 0.78/(1- 0.793)
=3.76

Likelihood Ratio
= (1- 0.78/0.793)
=0.28

Pretest Probability = 82/270


=0.30
=30%
Typhoid Fever

Disease Present Disease Absent

Test Positive 64 39
TYPHYDOT -M
TEST
Test Negative 18 149
Disease Disease
Total
Present Absent
Test Positive 67 29 96
TYPHIDOT M
Test Negative 15 159 174
TEST
Total 82 188 270

Sensitivity Positive Predictive Value


= 67/82 = 67/96
=0.817 =0.698
=81.7% =69.8%

Specificity Negative Predictive Value


= 159/188 = 159/174
=0.846 =0.914
=84.6% =91.4%
Likelihood Ratio +
= 0.817/(1- 0.846)
=5.30

Likelihood Ratio
= (1- 0.817)/0.846
=0.22

Pretest Probability
= 82/270
= 0.30
= 30%
SUMMARY OF THE RESULTS
Widal Test Typhidot-M

Sensitivity 78% 81.7%

Specificity 79.3% 84.6%

Positive Predictive Value 62.1% 69.8%

Negative Predictive Value 89.2% 91.4%


Likelihood Ratio + 3.76 5.30

Likelihood Ratio - 0.28 0.22

Pretest Probability 30% 30%


THANK YOU

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