validity of the widal test in the diagnosis of typhoid...
TRANSCRIPT
Validity of the Widal Test in theDiagnosis of Typhoid Fever among
Patients in Two General Hospitals inKaduna State, March – July, 2014
NIGERIA FIELD EPIDEMIOLOGY AND LABORATORY TRAINING PROGRAMME
Celestine A. Ameh1, S. Ahmed 2, M. Chori3 C.Benjamin4, S. Shehu2, A. Olayinka2
1. Nigeria Field Epidemiology and Laboratory Training Program
2. Ahmadu Bello University, Zaria, Nigeria
3. Barau Dikko Specialist Hospital, Kaduna , Nigeria
4. Yusuf Dantsoho Memorial Hospital, Kaduna, Nigeria
Introduction
• In 2010, there was an estimated 13.1million incident cases of Typhoid fever(TF) globally
• Africa accounted for 46% of this incidence• In Nigeria, prevalence of TF ranges from
39%-73.9%• Children between the ages of 1-10years
most affected
NIGERIA FIELD EPIDEMIOLOGY AND LABORATORY TRAINING PROGRAMME
• In 2010, there was an estimated 13.1million incident cases of Typhoid fever(TF) globally
• Africa accounted for 46% of this incidence• In Nigeria, prevalence of TF ranges from
39%-73.9%• Children between the ages of 1-10years
most affected2
Introduction...2
• Gold standard for diagnosis is bloodculture technique– Time consuming, expensive and technical
• The most common diagnostic approach isthe use of the Widal Test (WT)
• Inconsistency in Widal result from differenthealth facilities (Igharo et al,2012)
NIGERIA FIELD EPIDEMIOLOGY AND LABORATORY TRAINING PROGRAMME
• Gold standard for diagnosis is bloodculture technique– Time consuming, expensive and technical
• The most common diagnostic approach isthe use of the Widal Test (WT)
• Inconsistency in Widal result from differenthealth facilities (Igharo et al,2012)
3
Introduction...3
• Few studies have assessed validity inquantifying the diagnostic value of theWidal test
• We set out to determine the sensitivityand specificity of the Biosystems andSpectrum test kits and the level ofagreement in the results of these two kits
NIGERIA FIELD EPIDEMIOLOGY AND LABORATORY TRAINING PROGRAMME
• Few studies have assessed validity inquantifying the diagnostic value of theWidal test
• We set out to determine the sensitivityand specificity of the Biosystems andSpectrum test kits and the level ofagreement in the results of these two kits
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Methods
• Study area: Yusuf Danstoho and BarauDikko Specialist Hospital in Kadunametropolis
• Study design: A cross-sectional study• Study population: Febrile patients of all
age group
NIGERIA FIELD EPIDEMIOLOGY AND LABORATORY TRAINING PROGRAMME
• Study area: Yusuf Danstoho and BarauDikko Specialist Hospital in Kadunametropolis
• Study design: A cross-sectional study• Study population: Febrile patients of all
age group
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Methods...2
• Eligibility criteria: Febrile patients (axilliarytemp > 38º C) with either all or any of thefollowing symptoms: headache, vomitingand abdominal pain;
• Eligible patients who consented toparticipate in the study were systematicallyrecruited
NIGERIA FIELD EPIDEMIOLOGY AND LABORATORY TRAINING PROGRAMME
• Eligibility criteria: Febrile patients (axilliarytemp > 38º C) with either all or any of thefollowing symptoms: headache, vomitingand abdominal pain;
• Eligible patients who consented toparticipate in the study were systematicallyrecruited
6
Methods...3
Sample size determinationSensitivity of Widal test (P) = 50%
Prevalence of typhoid in Borno: 41.2% (Isa et al 2013)
Z score for 95% confidence level: 1.96
Level of precision(d): 5%
n = 384 = No. of infected patients detected
Therefore, Total No. of patients to be recruited = 384/0.42 = 915
(Banoo et al, 2006)
NIGERIA FIELD EPIDEMIOLOGY AND LABORATORY TRAINING PROGRAMME
Sample size determinationSensitivity of Widal test (P) = 50%
Prevalence of typhoid in Borno: 41.2% (Isa et al 2013)
Z score for 95% confidence level: 1.96
Level of precision(d): 5%
n = 384 = No. of infected patients detected
Therefore, Total No. of patients to be recruited = 384/0.42 = 915
(Banoo et al, 2006)
2
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Methods...4
• Sampling technique:– Using a daily sampling frame of 200, and a sampling
interval of 5, the first patient was randomly selected.Subsequently, every fifth patient was sampled untilthe sample size was attained
• Study instruments– Patients case files
– Laboratory request forms and worksheets
– A semi-structured questionnaire to assess patientsdemographic profile, antibiotic usage & clinical history
NIGERIA FIELD EPIDEMIOLOGY AND LABORATORY TRAINING PROGRAMME
• Sampling technique:– Using a daily sampling frame of 200, and a sampling
interval of 5, the first patient was randomly selected.Subsequently, every fifth patient was sampled untilthe sample size was attained
• Study instruments– Patients case files
– Laboratory request forms and worksheets
– A semi-structured questionnaire to assess patientsdemographic profile, antibiotic usage & clinical history
8
Methods...5
Laboratory methods:• Blood culture
– All non lactose fermenting (NLF) colonies measuringbetween 2-3mm in size on solid media were identifiedas Salmonella typhi if they fulfilled the followingidentification criteria as outlined:
– Hanging loop test-Motile, Triple Sugar Iron (TSIA)-Alkaline/Acid + Gas (H2S), Urease-Negative, Indole-Negative, Oxidase-Negative, Citrate-Positive
NIGERIA FIELD EPIDEMIOLOGY AND LABORATORY TRAINING PROGRAMME
Laboratory methods:• Blood culture
– All non lactose fermenting (NLF) colonies measuringbetween 2-3mm in size on solid media were identifiedas Salmonella typhi if they fulfilled the followingidentification criteria as outlined:
– Hanging loop test-Motile, Triple Sugar Iron (TSIA)-Alkaline/Acid + Gas (H2S), Urease-Negative, Indole-Negative, Oxidase-Negative, Citrate-Positive
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A7 See how the laboratory section can be reducedAJII, 3/11/2016
Methods...6
• Widal test– Slide and tube agglutination techniques was carried
out using standard procedure
– Widal test was considered positive if patient Widalagglutinin titre was ≥160 and if a 2 fold raise in titrewas observed in paired sera tested at two weeksinterval from the same patient, otherwise, it isnegative
– Widal test was considered negative if there was noagglutination in the Slide test or if paired sera showedno increase in tube agglutinin titre after 2 weeks
NIGERIA FIELD EPIDEMIOLOGY AND LABORATORY TRAINING PROGRAMME
• Widal test– Slide and tube agglutination techniques was carried
out using standard procedure
– Widal test was considered positive if patient Widalagglutinin titre was ≥160 and if a 2 fold raise in titrewas observed in paired sera tested at two weeksinterval from the same patient, otherwise, it isnegative
– Widal test was considered negative if there was noagglutination in the Slide test or if paired sera showedno increase in tube agglutinin titre after 2 weeks
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Methods...7
• The result of the tube Widal test wascompared to the blood culture result todetermine the Sensitivity and Specificity ofthe Biosystems and Spectrum Widal testkits
NIGERIA FIELD EPIDEMIOLOGY AND LABORATORY TRAINING PROGRAMME
• The result of the tube Widal test wascompared to the blood culture result todetermine the Sensitivity and Specificity ofthe Biosystems and Spectrum Widal testkits
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Statistical analysis
• Univariate analysis: Median andproportions
• Validity was calculated using Wilsonsmethod
• Reproducibility of the Widal result of theBiosystems and Spectrum kits wasassessed using Altman’s Standard kappastatistic
NIGERIA FIELD EPIDEMIOLOGY AND LABORATORY TRAINING PROGRAMME
• Univariate analysis: Median andproportions
• Validity was calculated using Wilsonsmethod
• Reproducibility of the Widal result of theBiosystems and Spectrum kits wasassessed using Altman’s Standard kappastatistic
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RESULTS
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Variable Frequency (%)Sex
Male 401(45.1)Female 489(54.9)
Age Group (yrs)< 10 273(30.70
Sociodemographic characteristics of eligiblepatients in Kaduna (2014)
NIGERIA FIELD EPIDEMIOLOGY AND LABORATORY TRAINING PROGRAMME
< 10 273(30.7010-19 304(34.2)20-29 107(12.0)30-39 79(8.90)40-49 64(7.2)50-59 29(3.2)>=60 34(3.8)
Median age 16 [Range: 1-91]
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Variable Frequency (%)Occupation
Paid employed 249(28.0)
Self employedUnemployed
133(14.9)508(57.1)
Educational status
Sociodemographic characteristics of eligiblepatients in Kaduna (2014)
NIGERIA FIELD EPIDEMIOLOGY AND LABORATORY TRAINING PROGRAMME
Self employedUnemployed
133(14.9)508(57.1)
Educational statusNone 262(29.4)
Primary 264(29.7)Secondary 254(28.5)
Tertiary 110(12.4)LGA
Kaduna North 377(42.3)Kaduna South 513(57.7)
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Validity of the Widal test using Biosystems andSpectrum Kits at a cut-off value of 1/160 in
Kaduna (2014)Kits Sensitivity
(%)CI (95%) Specificity
(%)CI (95%) PPV CI (95%) NPV CI (95%)
Biosystems
TO 56.3 48.3-63.9 85.8 83.1-88.1 44.7 37.8-51.8 90.6 88.2-92.5
TH
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TH 47.0 39.2-54.9 88.3 85.8-90.4 45.2 37.6-53.0 89.0 86.6-91.1Spectrum
TO 53.6 45.7-61.4 85.7 83.0-88.1 43.5 36.6-50.7 90.0 87.6-92.0
TH 41.0 33.5-49.0 87.9 85.4-90.1 41.0 33.5-49.0 87.9 85.4-90.1TO
Reproducibility of the Biosystems and Spectrumwidal kits at a cut-off value of 1/160 in Kaduna
(2014)
Widal Kits
WidalAntibodies
Biosystems Spectrum Kappa 95% CI
Anti TO
NIGERIA FIELD EPIDEMIOLOGY AND LABORATORY TRAINING PROGRAMME
Anti TO
Positive 186 190 0.89 0.85-0.92
Negative 704 700Anti TH
Positive 157 151 0.82 0.76-0.86
Negative 733 73917
DISCUSSION
NIGERIA FIELD EPIDEMIOLOGY AND LABORATORY TRAINING PROGRAMME
DISCUSSION
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Discussion
• Widal test showed a low sensitivity– Ability to detect those who have Typhoid fever
is low– More than half of the patients diagnosed as
having typhoid actually do not have thedisease
– Low diagnostic value
NIGERIA FIELD EPIDEMIOLOGY AND LABORATORY TRAINING PROGRAMME
• Widal test showed a low sensitivity– Ability to detect those who have Typhoid fever
is low– More than half of the patients diagnosed as
having typhoid actually do not have thedisease
– Low diagnostic value
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Discussion...2
• Widal test showed a moderate specificity– Ability to detect those who do not have the
disease is moderate– A waste of time and resources– A negative Widal test has little clinical value
NIGERIA FIELD EPIDEMIOLOGY AND LABORATORY TRAINING PROGRAMME
• Widal test showed a moderate specificity– Ability to detect those who do not have the
disease is moderate– A waste of time and resources– A negative Widal test has little clinical value
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Discussion...3
• Inter kit performance of Widal Kit iscomparable– Observed inconsistency of the Widal test less
likely to be due to kit standardization– Less likely to be due to testing proficiency
NIGERIA FIELD EPIDEMIOLOGY AND LABORATORY TRAINING PROGRAMME
• Inter kit performance of Widal Kit iscomparable– Observed inconsistency of the Widal test less
likely to be due to kit standardization– Less likely to be due to testing proficiency
21
Conclusion
• The Widal test which is an antibody basedtest has a low sensitivity and moderatespecificity
• Low Validity values not due to kitstandardization since kappa statisticshows comparability in test result
NIGERIA FIELD EPIDEMIOLOGY AND LABORATORY TRAINING PROGRAMME
• The Widal test which is an antibody basedtest has a low sensitivity and moderatespecificity
• Low Validity values not due to kitstandardization since kappa statisticshows comparability in test result
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Recommendation
• Health workers should be encouraged touse more valid tests in the diagnosis ofTyphoid fever
• Utility of new antigen based test should beexplored e.g. Typhidot
NIGERIA FIELD EPIDEMIOLOGY AND LABORATORY TRAINING PROGRAMME
• Health workers should be encouraged touse more valid tests in the diagnosis ofTyphoid fever
• Utility of new antigen based test should beexplored e.g. Typhidot
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Public Health Action
• Increased sensitization to Clinicians inthese two Hospitals on the outcome of ourfindings and on the need to discontinuewith the use of the Widal test
NIGERIA FIELD EPIDEMIOLOGY AND LABORATORY TRAINING PROGRAMME
• Increased sensitization to Clinicians inthese two Hospitals on the outcome of ourfindings and on the need to discontinuewith the use of the Widal test
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THANK YOU
NIGERIA FIELD EPIDEMIOLOGY AND LABORATORY TRAINING PROGRAMME
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Ethical considerations
• Written Informed consent was obtainedfrom all recruited participants
• Ethical approval was granted by the Ethicscommittee of the Kaduna State Ministry ofHealth
NIGERIA FIELD EPIDEMIOLOGY AND LABORATORY TRAINING PROGRAMME
• Written Informed consent was obtainedfrom all recruited participants
• Ethical approval was granted by the Ethicscommittee of the Kaduna State Ministry ofHealth
26
A10
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Limitations
• Information bias• Low level of Bacterial isolation
– Bactec would have given us a higher isolation
NIGERIA FIELD EPIDEMIOLOGY AND LABORATORY TRAINING PROGRAMME
• Information bias• Low level of Bacterial isolation
– Bactec would have given us a higher isolation
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A11
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