| Abstract|| |
Introduction: Typhoid fever still continues to be a major public health problem, particularly in developing countries. A simple, reliable, affordable, and rapid diagnostic test has been a long-felt need of the clinicians. We, therefore, prospectively evaluated the sensitivity and specificity of Typhidot (IgM), a serological test to identify IgM antibodies against Salmonella typhi. Materials and Methods: The study was carried out in the Department of Microbiology, Apollo Hospital, Bangalore between January 2009 and March 2009 on a total of 186 samples from clinically suspected febrile patients. Blood culture as well as Typhidot test was performed for each of the cases. Results: Out of 61 clinically diagnosed typhoid fever, 50 were blood culture positive for S. typhi all 50 were Typhidot (IgM) positive and 11 were missed out on both. The sensitivity, specificity, positive and negative predictive values of the test using blood culture as gold standard were 100%, 95.5%, 89.2%, and 100%, respectively for typhoid fever. Conclusion: Typhidot (IgM) test is rapid, easy to perform, and reliable for diagnosing typhoid fever, and useful for small, less equipped laboratories as well as for the laboratories with better facilities in typhoid endemic countries.
Keywords: Developing countries, Salmonella typhi, Typhoid fever, Typhidot (IgM) test
|How to cite this article:|
Krishna S, Desai S, Anjana V K, Paranthaaman R G. Typhidot (IgM) as a reliable and rapid diagnostic test for typhoid fever. Ann Trop Med Public Health 2011;4:42-4
|How to cite this URL:|
Krishna S, Desai S, Anjana V K, Paranthaaman R G. Typhidot (IgM) as a reliable and rapid diagnostic test for typhoid fever. Ann Trop Med Public Health [serial online] 2011 [cited 2014 Sep 20];4:42-4. Available from: http://www.atmph.org/text.asp?2011/4/1/42/80535
| Introduction|| |
Typhoid fever caused by Salmonella More Details typhi continues to be a major public health problem in developing countries and the incidence has been estimated at 540 cases per 100,000 of the population per year. The emergence of multidrug-resistant strains of S. typhi is known to be associated with significant morbidity and mortality. Equally recognized is the fact that a delay in diagnosis and institution of appropriate therapy may significantly increase the risk of adverse outcome and mortality. , Since the clinical presentation may not be specific; much onus falls on the laboratory for the rapid, reliable, and accurate early diagnosis of typhoid fever. The laboratory diagnosis directly depends on the day of illness and the investigation sought. Blood cultures carry 70-75% of diagnostic yield in the first week of illness and are still regarded as the gold standard for diagnosis  However, the delay in results stands inevitable. Rapid dot enzyme immunoassays have been tested and being used widely world over from a few years with varied results. ,,, Test is based on the presence of specific IgM antibodies to a specific 50 kDa outer membrane protein (OMP) antigen on S. typhi and becomes positive as early as in the first week of the fever, the results can be interpreted visually and available within one hour. To widen the clinical awareness, the study was undertaken with the objective to evaluate the sensitivity and specificity of the typhidot assays with blood cultures in the diagnosis of typhoid fever in our set-up.
| Materials and Methods|| |
The study was carried out at Apollo Hospital, Bangalore during the period Jan 2009 to March 2009. A total of 186 samples from febrile patients (irrespective of age groups) were serologically tested with typhidot assay as per the kit instructions (Biodiagnostic Research Sdn. Bhd, Selangor Darul Ehsan, Malaysia). An equal number of blood cultures (around 10 ml blood) were collected from the same patients and processed with Bact/Alert 240 (Biomerieux, France). Growth was further processed and identified as per the protocol recommended and followed in the laboratory.  The patients were categorized into four groups: Group I included patients with typhoid fever confirmed by isolation of S. typhi from blood culture; Group II included febrile patients with positive blood cultures other than S. typhi isolates. Group III consisted of patients whose clinical course was compatible with typhoid fever but whose blood culture was negative for S. typhi with at least six of the following criteria: a history of documented fever of five days or more, headache, constipation, diarrhea, rash, spleenomegaly, hepatomegaly, abdominal pain, nausea, signs of toxemia, leukopenia and/or leukocytosis, or response to antibiotic therapy for treatment of typhoid fever. 
| Results|| |
Out of 186 patients, 50 (64%) were culture positive for S. typhi (Group I) with 50 of the 50 tested positive for typhidot. Blood cultures also grew other organisms (Group II) - 22 isolates were identified as S. paratyphi, 4 were identified as S. typhimurium, and 2 were identified as E. coli and all of these 28 patients were typhidot positive. Blood cultures remained sterile and typhidot stood negative in rest of the other samples from patients with febrile illness (108). With the 2 × 2 table, the sensitivity of typhidot in relation to blood cultures was 100%, specificity was 95.5%, positive predictive value 89.2%, and negative predictive value 100% (22 patients with S. paratyphi A in blood culture were excluded in this analysis). Eleven patients (Group III) neither grew S. typhi nor were typhidot positive, but were treated on clinical evidence and recovered. [Table 1] depicts the results of the study.
| Discussion|| |
Based on the results, typhidot was found to be having maximum sensitivity (100%) and good specificity (95.5%). However, cross-reactions with S. paratyphi A (28.2%) were documented and regarded as inevitable. Bearing this on mind, our results show that there is 89.2% probability that the patient gets diagnosed as typhoid fever when tested by typhidot. Predictive value for a negative test was computed at 100%, which means given a negative typhidot, there is a 100% probability that the patient has no typhoid fever. Blood culture was found out to be positive in 75.7% of cases based on our criteria of clinical typhoid and none of the 11 cases were positive by typhidot. Results stand in liason with most of the published data over a decade worldwide as quoted in [Table 2]. Turn around time is less than one hour when compared to 1?2 days for blood cultures. Despite the time, blood cultures accompany sensitivity testing too, and thus enjoy the status of preferred choice in this decade of changing susceptibility pattern of Salmonella isolates. Our results support that laboratories could easily employ this rapid, economical test with no expert technical skill, apt for developing countries, or at field. In the multi-step approach to decrease the incidence of typhoid in tropical countries such as proper sanitation, safe drinking water, newer vaccines, and so on, early diagnosis and treatment also figures out prominently and typhidot could come in handy at the diagnostic laboratories.
|Table 2: Comparative evaluation of the typhidot tests in various studies|
Click here to view
| Conclusions|| |
Typhidot (Ig M) at our set-up showed high sensitivity and specificity and can be considered as the test of choice for the diagnosis of typhoid in today's rapid diagnostic era. Though blood culture continues to enjoy the status of a time-tested reliable gold standard, typhidot nonetheless can be used for the rapid and accurate diagnosis of typhoid fever in the typhoid endemic tropical countries.
| Acknowledgement|| |
The authors thank the patients, clinicians and administration, Apollo Hospitals, Bangalore. 
| References|| |
|1.||Jelinek T, Nothdurft HD, Sonnenburg FV, Loscher T. Risk factors for Typhoid fever in travelers. Journal of Travel Medicine 2006; 3:200-3. |
|2.||Rajeev Kumar, Nomeetha Gupta and Shalini. Multidrug Resistant Typhoid fever. Indian J Pediatr 2007; 74(1): 39-42 |
|3.||Hoffman SL, Punjabi Narain, Rockhill RC, Sutomo A, Rivai AR, Pulungsih SP. Duodenal string capsule compared with bone marrow blood and rectal swab cultures for diagnosing typhoid and paratyphoid fever. J Infect Dis 1984; 149:157-61. |
|4.||Ismail A, Kader SA, Ong KH. Dot enzyme immunosorbent assay for the serodiagnosis of typhoid fever. Southeast Asian J Trop Med Pub Health 1991; 22:563-6. |
|5.||Lu-Fong M, Ludan AC, Martinez MM, Raymundo JG. Dot EIA (Typhidot): An aid to the diagnosis of typhoid fever among Filipino children. Malaysian J Child Health 1999;8:163. |
|6.||Olsen SJ, Pruckler J, Bibb W, Thanh NTM, Trinh TM, Minh NT, et al. Evaluation of rapid diagnostic tests for typhoid fever. J Clin Microbiol 2004; 42:1885-9. |
|7.||Collantes E, Velmonte AM. The validity of the typhidot test in diagnosing typhoid fever among Filipinos. Phil J Microbiol Infect Dis 1997; 26:61-3. |
|8.||Koneman EW, Allen SD, Janda WM, Schreckenberger PC, Winn WC. Color Atlas and Textbook of Diagnostic Microbiology. 5 th ed. NY: Lippincott; 1997. |
|9.||Harrison's principle of Internal Medicine: Salmonellosis. In: Fauci AS, Brawnwald E, Kasper DL, Stephan L Hauser, Longo DL, Jameson JL, et al. 17 th edition. Part 7. US: Infectious Diseases Mc Graw Hill companies; 2008. |
|10.||Membrebe FA, Chua JA. The clinical utility of typhidot in the diagnosis of typhoid fever. Phil J Microbiol Infect Dis 1999; 28:1-4. |
|11.||Jesudason MV, Sivakumar S. Prospective evaluation of a rapid diagnostic test Typhidot for typhoid fever. Indian J Med Res 2006; 123:513-6. |
|12.||Begum Z, Hossain MA, Shamsuzzaman AK, Ahsan MM, Musa AK, Mahmud MC, et al. Evaluation of Typhidot (IgM) for early diagnosis of typhoid fever. Bangladesh J Med Microbiol 2009; 3:10-3. |
|13.||Choo KE, Oppenheimer SJ, Ismail AB, Ong KH. Rapid serodiagnosis of typhoid fever by dot enzyme immunoassay in an endemic area. Clin Infect Dis 1994; 19:172-6. |
|14.||Choo KE, Davis TM, Ismail A, Ibrahim TA, Ghazali WN. Rapid and reliable serological diagnosis of enteric fever: Comparative sensitivity and specificity of Typhidot and Typhidot-M tests in febrile Malaysian children. Acta Tropica 1999; 72:175-83. |
|15.||Narayanappa D, Sripathi R, Jagdishkumar K, Rajani HS. Comparative study of Dot Enzyme Immunoassay (Typhidot-M) and Widal test in the diagnosis of typhoid fever. Indian Pediatr 2010; 47:331-3. |
Assistant Professor, Department of Microbiology, Amrita Institute of Medical Sciences, Cochin-682041 Kerala
[Table 1], [Table 2]