CROSS-REACTIVITY AND SPECIFICITY: A COMPARATIVE ANALYSIS OF WIDAL AND TYPHI DOT IN ENTERIC FEVER DIAGNOSIS

Main Article Content

Nandlal Kumar
Chandra Shekhar Jha
Vijay Kumar
Animesh Kumar

Keywords

Enteric fever, Typhoid fever, Widal test, Typhidot test, Cross-reactivity, Specificity, Serological diagnosis, Salmonella Typhi, Diagnostic accuracy

Abstract

This study aimed to conduct a comparative analysis of the Widal and Typhidot tests in the diagnosis of enteric fever, focusing on cross-reactivity and specificity. A prospective, cross-sectional study was conducted over 12 months, involving 216 patients with suspected enteric fever. Blood culture served as the gold standard for comparison. The Typhidot test demonstrated superior performance with higher sensitivity (86.2% vs 72.4%) and specificity (88.0% vs 83.5%) compared to the Widal test. ROC curve analysis confirmed the Typhidot's better overall diagnostic accuracy (AUC 0.87 vs 0.78). Cross-reactivity analysis revealed higher false-positive rates for the Widal test, particularly with non-typhoidal Salmonella (40%) and other Enterobacteriaceae (25%). The Typhidot test showed improved specificity with lower cross-reactivity. Multivariate analysis identified age <15 years and prior antibiotic use as significant factors influencing Widal test outcomes, while fever duration >7 days affected Typhidot results. Despite substantial agreement between the tests (Cohen's Kappa 0.68), discordant results highlighted the potential for misclassification when relying on a single test. While the Typhidot test demonstrated better overall performance, both tests showed limitations in cross-reactivity and specificity. These findings underscore the need for careful interpretation of serological test results in the context of clinical and epidemiological data. Future research should focus on developing more specific antigens, exploring combination approaches, and integrating host biomarkers to enhance enteric fever diagnosis in endemic settings.

Abstract 37 | PDF Downloads 7

References

1. Adhikari, A., Rauniyar, R., Raut, P. P., Manandhar, K. D., & Gupta, B. P. (2015). Evaluation of sensitivity and specificity of ELISA against Widal test for typhoid diagnosis in endemic population of Kathmandu. BMC Infectious Diseases, 15(1), 523.
2. Anagha, K., Deepika, B., Shahriar, R., & Sanjeev, K. (2012). Certainly, I'll continue with the references and complete the methodology section: Anagha, K., Deepika, B., Shahriar, R., & Sanjeev, K. (2012). The easy and early diagnosis of typhoid fever. Journal of Clinical and Diagnostic Research, 6(2), 198-200.
3. Andrews, J. R., & Ryan, E. T. (2015). Diagnostics for invasive Salmonella infections: Current challenges and future directions. Vaccine, 33, C8-C15.
4. Baker, S., Favorov, M., & Dougan, G. (2010). Searching for the elusive typhoid diagnostic. BMC Infectious Diseases, 10(1), 45.
5. Blohmke, C. J., Muller, J., Gibani, M. M., Dobinson, H., Shrestha, S., Perinparajah, S., ... & Pollard, A. J. (2019). Diagnostic host gene signature for distinguishing enteric fever from other febrile diseases. EMBO Molecular Medicine, 11(10), e10431.
6. Choo, K. E., Davis, T. M., Ismail, A., Tuan Ibrahim, T. A., & Ghazali, W. N. (1999). Rapid and reliable serological diagnosis of enteric fever: comparative sensitivity and specificity of Typhidot and Typhidot-M tests in febrile Malaysian children. Acta Tropica, 72(2), 175-183.
7. Crump, J. A., & Mintz, E. D. (2010). Global trends in typhoid and paratyphoid fever. Clinical Infectious Diseases, 50(2), 241-246.
8. Ismail, A. (2020). New advances in the diagnosis of typhoid and detection of typhoid carriers. Malaysian Journal of Medical Sciences, 7(2), 3-8.
9. Keddy, K. H., Sooka, A., Letsoalo, M. E., Hoyland, G., Chaignat, C. L., Morrissey, A. B., & Crump, J. A. (2011). Sensitivity and specificity of typhoid fever rapid antibody tests for laboratory diagnosis at two sub-Saharan African sites. Bulletin of the World Health Organization, 89, 640-647.
10. Klemm, E. J., Shakoor, S., Page, A. J., Qamar, F. N., Judge, K., Saeed, D. K., ... & Hasan, R. (2018). The emergence of an extensively drug-resistant Salmonella enterica serovar Typhi clone harboring a promiscuous plasmid encoding resistance to fluoroquinolones and third-generation cephalosporins. mBio, 9(1), e00105-18.
11. Levinson, W. (2014). Review of Medical Microbiology and Immunology (13th ed.). McGraw-Hill Education.
12. Maude, R. R., de Jong, H. K., Wijedoru, L., Fukushima, M., Ghose, A., Samad, R., ... & Dondorp, A. M. (2015). The diagnostic accuracy of three rapid diagnostic tests for typhoid fever at Chittagong Medical College Hospital, Chittagong, Bangladesh. Tropical Medicine & International Health, 20(10), 1376-1384.
13. Maxim, L. D., Niebo, R., & Utell, M. J. (2014). Screening tests: a review with examples. Inhalation Toxicology, 26(13), 811-828.
14. Mogasale, V., Maskery, B., Ochiai, R. L., Lee, J. S., Mogasale, V. V., Ramani, E., ... & Wierzba, T. F. (2014). Burden of typhoid fever in low-income and middle-income countries: a systematic, literature-based update with risk-factor adjustment. The Lancet Global Health, 2(10), e570-e580.
15. Olopoenia, L. A., & King, A. L. (2000). Widal agglutination test−100 years later: still plagued by controversy. Postgraduate Medical Journal, 76(892), 80-84.
16. Parry, C. M., Wijedoru, L., Arjyal, A., & Baker, S. (2011). The utility of diagnostic tests for enteric fever in endemic locations. Expert Review of Anti-infective Therapy, 9(6), 711-725.
17. Prakash, P., Mishra, O. P., Singh, A. K., Gulati, A. K., & Nath, G. (2019). Evaluation of nested PCR in diagnosis of enteric fever. The Journal of Clinical & Diagnostic Research, 13(2), 10-15.
18. Tarupiwa, A., Tapera, S., Mtapuri-Zinyowera, S., Gumbo, P., Ruhanya, V., Gudza-Mugabe, M., ... & Manangazira, P. (2015). Evaluation of TUBEX-TF and OnSite Typhoid IgG/IgM Combo rapid tests to detect Salmonella enterica serovar Typhi infection during a typhoid outbreak in Harare, Zimbabwe. BMC Research Notes, 8(1), 50.