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Aims and Objectives: In the study we compare the sensitivity and specificity of two commonly used rapid serological test, Widal test and Typhidot, in the diagnosing of Typhoid fever. Material and Methods: Serum samples coming to the microbiology laboratory for routine testing over the period from September 2019 to November 2020 were analysed for the comparison for the presence of the Salmonella antibodies by carrying out the Typhidot and Widal tube agglutination test in tertiary care centre. Results: Out of 580 blood specimen, 49.3% cases were positive by Typhidot and 38.6% cases were positive by Widal method. Conclusion: Typhidot is a rapid and more sensitive test for early diagnosis of typhoid fever. It is now commercially available for the diagnosis of typhoid fever in areas with limited resources.Widal test showed the sensitivity and specificity of 37% & 62.4% respectively. Typhi dot test showed sensitivity of 41.4% and specificity of 56.5%. Keywords: Rapid test, Widal test, Typhidot test, serological test.

Introduction: Typhoid is a bacterial infection that can lead to a high fever, diarrhoea, and vomiting. It can be fatal. It is caused by the bacteria Salmonella typhi. Globally, around 21.5 million people a year contract typhoid. If typhoid is caught early, it can be successfully treated with antibiotics; if it is not treated, typhoid can be fatal. Materials and Methods: This is a retrospective and observational study conducted in Department of Pediatrics from the 1 January 2016 to 30 December 2019. Epidemiological data, clinical features, blood culture, Typhidot IgM test and other laboratory parameters from all the patients were collected and it was analyzed by using the Statistical package for social sciences (SPSS) version 21 Fisher’s exact test. Results: During the study period total 290 febrile patients with symptoms suggestive of Enteric fever were included. Incidence of enteric fever among these 290 patients was 32.41% (n=94), of which laboratory confirmed culture positive incidence was 17.09% (n=55) and probable cases of enteric fever based on positive serodiagnosis where culture showed no growth was 17.09% (n=39). Out of 290 patients, 170 (58.62%) were male and rest 120 (41.37%) were female. The serological positivity by Widal test in this study was 32.06% (n=93/290). Serodiagnosis by Typhidot IgM was 27.24% (n=79/290). Conclusions: High rate of MDR S. Typhi is alarming and suggests need for better living standards, health education, correct diagnosis and proper treatment as control strategies. Keywords: Salmonella Typhi, Enteric Fever, Widal Test, Typhidot.

Background: The term enteric fever includes typhoid fever caused by Salmonella typhi and paratyphoid fever caused by Salmonella paratyphi A, B, and C. Typhoid fever has been virtually eliminated in the developed countries during the past several decades, mainly as a result of improvement in water supply and sanitation, but it continues to be endemic in the resource-limited nations of the world. The control of paratyphoid fever has not been so successful. Bacteriological diagnosis of enteric fever consists of isolation of the bacilli from the patients and the demonstration of antibodies in their sera. Widal testing is cost-effective and gives reports quickly. The Typhidot test is based on the method of immunochromatography test. It is easy to perform, and the results can be preserved for a long time. This study aims to compare the sensitivity and specificity of the Widal test and Typhidot test for the diagnosis of enteric fever. Materials and Methods: This prospective study was carried out at the Department of Microbiology, N.C. Medical College and Hospital, Panipat, Haryana, India, over 6 months from September 2020 to February 2021. In our study, a total of 150 clinically suspected patients were included. First of all, the area for blood collection was cleaned with spirit-soaked cotton and 10 mL of blood was collected with a sterile disposable needle and syringe from a median cubital vein (antecubital vein) of each patient after obtaining informed consent from the patient (from parents in case of age below 18 years). Seven milliliters of blood was immediately transferred to a blood culture bottle by cleaning the cap of the bottle for isolation and identification of causative organisms and 3 mL was transferred to a sterile plain vial for serum separation. Then the qualitative Widal slide agglutination test and Typhidot test were performed on each sample. Results: In the present study, out of the 150 clinically suspected enteric fever cases, maximum positivity 53 (35.33%) was given by the Typhidot test, followed by 36 (24%) given by the qualitative Widal slide agglutination test and 44 (29.33%) given by blood culture for S. typhi and S. paratyphi. Conclusion: Our study highlights the use of Typhidot for early diagnosis of enteric fever and also cross-checks with Widal test and blood culture for the diagnosis of enteric fever. Typhidot tests are easy to perform and less-trained personnel can also perform the test; they have been designed to detect IgM and IgG antibodies to lipopolysaccharide or outer membrane protein antigens of S. typhi and S. paratyphi. It can be useful in the early diagnosis of infection in the initial weeks of primary infection when a single serum sample is available, with a sensitivity and specificity of 90% and 80%, respectively, considering blood culture as a gold standard.

Typhoid is an endemic in Fiji with increases observed since the early 2000s and frequent outbreaks reported. We assessed the diagnostic accuracy of currently available typhoid rapid diagnostic tests (RDTs) (TUBEX, Typhidot Rapid, and Test-It assay) to establish their performance against blood culture in Fiji and to examine their suitability for rapid typhoid outbreak identification. The performance of RDTs was assessed in the public health reference laboratory in Suva, Fiji, according to the manufacturers’ instructions. A simulation was used to examine the potential use of RDTs for attribution of a febrile illness outbreak to typhoid. For the diagnostic evaluation, 179 patients were included; 49 had blood culture–confirmed typhoid, 76 had fever as a result of non-typhoid etiologies, and 54 were age-matched community controls. The median (interquartile range) age was 29 (20–46) years. Of the participants, 92 (51.4%) were male and 131 (73.2%) were indigenous Fijians. The sensitivities of the tests were 77.6% for TUBEX, 75.5% for Typhidot Rapid, and 57.1% for Test-It assay. The Test-It assay had the highest specificity of 93.4%, followed by Typhidot Rapid 85.5% and TUBEX 60.5%. Typhidot Rapid had the best performance in the simulation for attribution of a febrile illness outbreak to typhoid. Typhoid RDTs performed suboptimally for individual patient diagnosis due to low sensitivity and variable specificity. We demonstrate that RDTs could be useful in the field for rapid attribution of febrile illness outbreaks to typhoid. Typhidot Rapid had the best combination of sensitivity, specificity, positive and negative predictive values, cost, and ease of use for this purpose.

This review discusses currently available serological diagnostic methods for typhoid fever with a focus on the clinical utility of TUBEX® TF as an alternative to the Widal or Typhidot test. A literature search was conducted in PubMed for related publications written in English. A qualitative analysis was done to determine various serological tests used for typhoid fever diagnosis with emphasis on TUBEX® TF in comparison to the Widal of Typhidot test. Further, a meta-analysis was performed to obtain a pooled estimate of diagnostic accuracy (sensitivity and specificity) using different analysis models. A total of sixteen studies was included in the qualitative analysis. Further screening of these studies yielded ten studies that were used for the meta-analysis. The sensitivity/specificity range of different commonly used serological tests in typhoid patients is between 55-100%/58-100% for TUBEX® TF, 54-67%/54-95% for Typhidot, and 32-95%/4-98% for the Widal test. As for the pooled meta-analysis estimates, the TUBEX® TF showed superior results when differentiating individuals with febrile illness of unknown origin from those with typhoid fever. Overall, the results of this review and meta-analysis suggest that the TUBEX® TF is more advantageous to use as a serological test for typhoid fever diagnosis due its accuracy and simplicity. However, further studies are still needed to validate our results.

Background and Study Aim: Typhoid (Enteric) fever is a systemic infection caused by Salmonella Typhi and Salmonella Paratyphi. It is endemic in the developing countries including Egypt. Different diagnostic tools can achieve diagnosis and include cultures from the blood, stool, bone marrow, rarely urine for isolation of the organism. Antibody detection by Widal test and relatively recent typhoid are also used. The current study aimed at comparing the most commonly used antibody detection Widal test with the rapid antibody detection typhidot for diagnosis of typhoid fever among Egyptian adults. Patients and Methods: The study included 140 patients who are presented with picture suggestive of typhoid fever. Confirmed cases after the blood culture were included in the final analysis. Widal and typhidot tests were performed in all patients and were compared for sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy. Results: 45 patients out of 140 were diagnosed as typhoid fever by blood culture. Out of them, Widal test was positive in 39 patients with sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy of 86.7%, 89.5%, 79.5%, 93.4% and 88.5% respectively. Typhidot test was positive in 42 patients with sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy of 93.3%, 90.6%, 82.3%, 96.6%, and 91.4% respectively (P = 0.00). Conclusions: Typhidot test is reliable, simple highly sensitive and specific test in diagnosing typhoid fever when compared with Widal test.

CONTEXT: To the best of our knowledge, there are no reports of serological evidence of human leptospirosis from Uttarakhand state in India. AIMS: The aim of this study was to screen for serological evidence of leptospirosis in patients with acute undifferentiated febrile illness at a tertiary care teaching hospital in Uttarakhand. SETTINGS AND DESIGN: A pilot study was conducted from March to November 2017. SUBJECTS AND METHODS: Fifty-three adult patients who presented in Medicine outpatient Department with a history of fever of ≥7 up to 14 days duration with or without other associated symptoms such as a headache, rashes, myalgia, arthralgia, and conjunctival suffusion were enrolled in the study using convenience sampling technique. Blood samples of these patients were collected and subjected to peripheral smear examination for malaria parasites, dengue immunoglobulin M (IgM) immunochromatographic card test, IgM Typhidot, Leptospira and Scrub typhus IgM ELISA, respectively. Aerobic blood culture was performed in 24 cases. Relevant clinico-epidemiological details were obtained as per the pro forma formulated in accordance with the modified Faine’s criteria. STATISTICAL ANALYSIS USED: Descriptive statistics. RESULTS: The study population consisted of 50.94% of males and 49.06% of females with a mean age ± standard deviation of 34.2 ± 15.2 years. Fifty febrile patients had additional symptoms of which myalgia was the most common (81.1%) followed by arthralgia (22.6%). Peripheral smears of all patients were negative for malaria parasites. Dengue and Typhidot IgM positivity was observed in two and eight patients, respectively. Six and five patients were tested positive by leptospira and scrub typhus IgM ELISA, respectively. Salmonella Typhi was isolated from blood sample of only one patient. Serum samples of two patients showed dual positivity. All six leptospira seropositive patients satisfied modified Faine’s criteria. CONCLUSIONS: Leptospirosis is a seemingly unexplored infection in Uttarakhand and should be considered as a differential diagnosis in patients with acute undifferentiated febrile illness.

A 6 year old girl presented with a history of fever for 3 weeks, headache and multifocal seizures for 4 days with altered sensorium. Clinical assessment was consistent with hypotensive shock and encephalopathy. Her IgM and IgG Typhidot test was positive. Laboratory evaluation revealed deranged renal and liver functions with coagulopathy, anemia and thrombocytopenia. She did not respond to broad spectrum intravenous antibiotics, vaso-active infusions, corticosteroids and had refractory status epilepticus. She progressed rapidly to refractory septic shock and multiple organ dysfunction with AKI and ARDS. She succumbed to her illness despite antibiotics and other adjunctive therapies. This case highlights a rare and catastrophic presentation of typhoid fever.

Objective: To determine and compare the performance of TUBEX® TF, widal test & blood culture in the diagnosis of enteric fever. Methods: After approving with the ethical committee, we retrospectively identified patients presented with fever at Northwest General Hospital and Research Centre. Typhidot, Widal test and blood culture was performed as part of their evaluation from January 2018 to December 2018. SPSS 16 was used for data analysis. Results: Of the 241 patients, blood culture was positive for salmonella in 68(28.21%) and negative in 173(71.79%). In the culture positive group, TUBEX® TF was positive in 29(42.64%) and negative in 39(57.36%). Of these culture positive patients, Widal was positive in 25(36.76%) and negative in 43(63.24%). In patients with negative culture, TUBEX® TF was positive in 58(37.66%) and negative in 96(62.34%), Widal was positive in 77(44.5%) and negative in 96(55.5%). The positive predictive value of TUBEX® TF was 33.33% and the negative predictive value was 71.77%. The sensitivity of TUBEX® TF was 42.65% while specificity was 62.34%. The positive predictive value of Widal was 24.51% and the negative predictive value was 69.06%. The sensitivity of Widal was 36.76% while specificity was 55.49%. Conclusion: Sensitivity, specificity, positive predictive value and negative predictive value of TUBEX® TF and Widal test is very low as compared to blood culture. Keywords: Enteric Fever, TUBEX® TF, Widal, Continuous...

Background Differentiating both typhoid (Salmonella Typhi) and paratyphoid (Salmonella Paratyphi A) infection from other causes of fever in endemic areas is a diagnostic challenge. Although commercial point-of-care rapid diagnostic tests (RDTs) for enteric fever are available as alternatives to the current reference standard test of blood or bone marrow culture, or to the widely used Widal Test, their diagnostic accuracy is unclear. If accurate, they could potentially replace blood culture as the World Health Organization (WHO)-recommended main diagnostic test for enteric fever. Objectives To assess the diagnostic accuracy of commercially available rapid diagnostic tests (RDTs) and prototypes for detecting Salmonella Typhi or Paratyphi A infection in symptomatic persons living in endemic areas. Search methods We searched the Cochrane Infectious Diseases Group Specialized Register, MEDLINE, Embase, Science Citation Index, IndMED, African Index Medicus, LILACS, ClinicalTrials.gov, and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) up to 4 March 2016. We manually searched WHO reports, and papers from international conferences on Salmonella infections. We also contacted test manufacturers to identify studies. Selection criteria We included diagnostic accuracy studies of enteric fever RDTs in patients with fever or with symptoms suggestive of enteric fever living in endemic areas. We classified the reference standard used as either Grade 1 (result from a blood culture and a bone marrow culture) or Grade 2 (result from blood culture and blood polymerase chain reaction, or from blood culture alone). Data collection and analysis Two review authors independently extracted the test result data. We used a modified QUADAS-2 extraction form to assess methodological quality. We performed a meta-analysis when there were sufficient studies for the test and heterogeneity was reasonable. Main results Thirty-seven studies met the inclusion criteria and included a total of 5080 participants (range 50 to 1732). Enteric fever prevalence rates in the study populations ranged from 1% to 75% (median prevalence 24%, interquartile range (IQR) 11% to 46%). The included studies evaluated 16 different RDTs, and 16 studies compared two or more different RDTs. Only three studies used the Grade 1 reference standard, and only 11 studies recruited unselected febrile patients. Most included studies were from Asia, with five studies from sub-Saharan Africa. All of the RDTs were designed to detect S.Typhi infection only. Most studies evaluated three RDTs and their variants: TUBEX in 14 studies; Typhidot (Typhidot, Typhidot-M, and TyphiRapid-Tr02) in 22 studies; and the Test-It Typhoid immunochromatographic lateral flow assay, and its earlier prototypes (dipstick, latex agglutination) developed by the Royal Tropical Institute, Amsterdam (KIT) in nine studies. Meta-analyses showed an average sensitivity of 78% (95% confidence interval (CI) 71% to 85%) and specificity of 87% (95% CI 82% to 91%) for TUBEX; and an average sensitivity of 69% (95% CI 59% to 78%) and specificity of 90% (95% CI 78% to 93%) for all Test-It Typhoid and prototype tests (KIT). Across all forms of the Typhidot test, the average sensitivity was 84% (95% CI 73% to 91%) and specificity was 79% (95% CI 70% to 87%). When we based the analysis on the 13 studies of the Typhidot test that either reported indeterminate test results or where the test format means there are no indeterminate results, the average sensitivity was 78% (95% CI 65% to 87%) and specificity was 77% (95% CI 66% to 86%). We did not identify any difference in either sensitivity or specificity between TUBEX, Typhidot, and Test-it Typhoid tests when based on comparison to the 13 Typhidot studies where indeterminate results are either reported or not applicable. If TUBEX and Test-it Typhoid are compared to all Typhidot studies, the sensitivity of Typhidot was higher than Test-it Typhoid (15% (95% CI 2% to 28%), but other comparisons did not show a difference at the 95% level of CIs. In a hypothetical cohort of 1000 patients presenting with fever where 30% (300 patients) have enteric fever, on average Typhidot tests reporting indeterminate results or where tests do not produce indeterminate results will miss the diagnosis in 66 patients with enteric fever, TUBEX will miss 66, and Test-It Typhoid and prototype (KIT) tests will miss 93. In the 700 people without enteric fever, the number of people incorrectly diagnosed with enteric fever would be 161 with Typhidot tests, 91 with TUBEX, and 70 with Test-It Typhoid and prototype (KIT) tests. The CIs around these estimates were wide, with no difference in false positive results shown between tests. The quality of the data for each study was evaluated using a standardized checklist called QUADAS-2. Overall, the certainty of the evidence in the studies that evaluated enteric fever RDTs was low. Authors' conclusions In 37 studies that evaluated the diagnostic accuracy of RDTs for enteric fever, few studies were at a low risk of bias. The three main RDT tests and variants had moderate diagnostic accuracy. There was no evidence of a difference between the average sensitivity and specificity of the three main RDT tests. More robust evaluations of alternative RDTs for enteric fever are needed. The accuracy of rapid diagnostic tests for detecting typhoid and paratyphoid (enteric) fever Cochrane researchers assessed the accuracy of commercially-available rapid diagnostic tests and their prototypes (including TUBEX, Typhidot, Typhidot-M, Test-it Typhoid, and other tests) for detecting typhoid and paratyphoid (enteric) fever in people living in countries where the estimated number of individuals with the disease at any one time is greater than 10 per 100,000 population. If accurate, they could replace the current World Health Organization (WHO)-recommended diagnostic test: culture (growing the bacteria that causes the infection from a patient’s blood or bone marrow). Background Typhoid fever and paratyphoid fever are infections caused by the bacteria Salmonella Typhi and Salmonella Paratyphi A respectively. The term ‘enteric fever’ is used to describe both infections. Enteric fever can be difficult to diagnose as the signs and symptoms are similar to those of other infectious diseases that cause fever such as malaria. The recommended test to confirm if a person has enteric fever is to grow the Salmonella from their blood. It takes at least 48 hours to give a result, so cannot help healthcare workers make a diagnosis the same day the blood culture is taken. Blood cultures may give a negative result even though a person has enteric fever. The test also requires a laboratory and trained staff, which are often unavailable in communities where enteric fever is common. Rapid diagnostic tests (RDTs) are designed to be easy to use, and to deliver a quick result without the need for a blood culture laboratory. The cost of an enteric fever RDT would be significantly less than a blood culture, and requires less training to perform. Study characteristics Cochrane researchers searched the available literature up to 4 March 2016 and included 37 studies. Most studies recruited participants from South Asia. Most participants were adults, with 22 studies including children. All of the RDTs evaluated detected Salmonella Typhi (typhoid fever) only. Quality of the evidence The Cochrane researchers evaluated the quality of the data for each study using a standardized checklist called QUADAS-2. High quality studies that compared different types of RDT in the same patients were few in number. Two-thirds of the included studies did not evaluate the RDTs in the context of patients who are typically tested for the disease. Many studies utilized a particular study design (a case control study) which risks overestimating RDT accuracy. In the studies evaluating the Typhidot RDT, it was often unclear how many test results were indeterminate, when the test cannot distinguish a current episode of infection from a previous disease episode. Overall, the certainty of the evidence in the studies that evaluated enteric fever RDTs was low. Key results Sensitivity indicates the percentage of patients with a positive test result who are correctly diagnosed with disease. Specificity indicates the percentage of patients who are correctly identified as not having disease. TUBEX showed an average sensitivity of 78% and specificity of 87%. Typhidot studies, grouped together to include Typhidot, Typhidot-M, and TyphiRapid-Tr02, showed an average sensitivity of 84% and specificity of 79%. When Typhidot studies with clear reporting of indeterminate results are considered, the average sensitivity and specificity of Typhidot was 78% and 77% respectively. Test-It Typhoid and prototypes (KIT) showed an average sensitivity of 69% and specificity of 90%. Based on these results, in 1000 patients with fever where 30% (300 patients) have enteric fever, we would expect Typhidot tests reporting indeterminate results or where tests do not produce indeterminate results to, on average, miss the diagnosis (give a false negative result) in 66 patients with enteric fever, TUBEX to miss 66, and Test-It Typhoid and prototypes (KIT) to miss 93. In the 700 people without enteric fever, the number of people incorrectly given a diagnosis of enteric fever (a false positive result) would be on average 161 with these Typhidot tests, 91 with TUBEX, and 70 with the Test-It Typhoid and prototypes (KIT). These differences in the number of false negative and false positive results in patients from the different tests are not statistically important. The RDTs evaluated are not sufficiently accurate to replace blood culture as a diagnostic test for enteric fever.

Background. The diagnosis of typhoid fever based on the Widal slide agglutination test remains a major hurdle in developing countries due to varied perceptions of the value of the Widal test in determining clinical decision-making. We undertook a study to evaluate the diagnostic performance of the Widal test and the Typhidot immunoassay in patients suspected of having typhoid fever in the Menoua division, West Region of Cameroon. Methods. Blood and stool samples were collected from 558 consenting febrile patients on the basis of suspicion of typhoid fever. These patients attended three district health services of the Menoua division between April 2018 and September 2019. These patients had clinical symptoms suggestive of typhoid fever as determined by their consultant. Serum was used for the Widal slide agglutination test and for the Typhidot rapid immunoassay test based on manufacturer’s guidelines. A composite reference of fever plus positive coproculture for Salmonella typhi and Salmonella paratyphi was used as the reference. The sensitivity, specificity, and predictive values of the positive and negative tests were calculated as well as Cohen’s kappa for agreement between the two tests. Results. Of 558 patients, 12.90% tested positive for the reference method, 57.17% tested positive for the Widal slide agglutination test, while 15.59% were positive for Typhidot-IgM. The overall sensitivity, specificity, and predictive values of the positive and negative tests were 80.56%, 94.03%, 66.6%, and 97.03% for Typhidot-IgM and 94.44%, 48.35%, 21.32%, and 98.33% for the Widal slide agglutination test, respectively. Cohen’s kappa estimates were 0.1660 (0.121–0.211) and 0.386 (0.312–0.460) for the Widal test and Typhidot immunoassay for 53.6% and 76.16% agreements of all observations, respectively. Conclusion. The Widal test was found to have a lower predictive value for the diagnosis of typhoid fever in our setting. However, the Typhidot test, although better, was not ideal. Diagnosis of typhoid fever should therefore rely on adequate clinical suspicion and a positive Typhidot test to improve the clinical management of typhoid fever in our setting.

Background: The diagnosis of Typhoid fever, based on the Widal slide agglutination test, remains a major hurdle in developing countries like Cameroon due to varied perceptions of the value of the Widal test in determining clinical decision making. We undertook a study to evaluate the diagnostic performance of the Widal test and the typhidot immunoassay in patients suspected of having typhoid fever in the Menoua division, West Region of Cameroon. Methods: Blood and stool samples were collected from 558 consenting febrile patients on the basis of suspicion of typhoid fever. These patients attended three district health services of the Menoua division between April 2018 and September 2019. These patients had clinical symptoms suggestive of typhoid fever as determined by their consultant. Serum from whole blood was used for the Widal slide agglutination test and for the Typhidot rapid immunoassay test based on manufacturer’s guidelines. A composite reference of fever plus positive coproculture for Salmonella enteric serovars typhi and paratyphi was used as reference. The sensitivity, specificity, predictive values of the positive and negative tests were calculated as well as the Cohen’s Kappa for agreement between the two tests. Results: Of 558 patients, 12.90% tested positive for the reference method, 57.17% tested positive for the Widal slide agglutination test while 15.59% were positive for typhidot-IgM. The overall sensitivity, specificity, predictive values of the positive and negative tests were 80.56%, 94.03%, 66.6% and 97.03% respectively for typhidot-IgM; 94.44%, 48.35%, 21.32% and 98.33% for Widal slide agglutination test. The Cohen’s kappa estimates were 0.1660 (0.121-0.211), 0.386 (0.312-0.460) for Widal test and typhidot immunoassay respectively, with agreements of 53.76% and 76.16% respectively. Conclusion: The Widal test was found to have a lower predictive value for the diagnosis of typhoid fever in our setting. However, the Typhidot test, although better, was not ideal. Diagnosis of typhoid fever should therefore rely on adequate clinical suspicion and a positive Typhidot test to improve the clinical management of Typhoid fever in our setting.

Objective: Laboratory study to assess the correlation of existing Salmonella blood culture isolates with Widal agglutinin titers and EIA-based Typhidot immunoassay antibodies as the gold standard. Materials and Methods: This study was conducted at the department of community medicine KEMU Lahore for six months from June 2017 to November 2018. 2704 blood samples were taken for cultural studies and Widal test in a clinical laboratory among people with symptoms of clinical intestinal fever. Of these, 1497 were isolated from Salmonella; The sera of these patients who did not accompany Typhidot requests were also subjected to spot immunoassay with the informed consent required for bleeding. All sera were stored at 40 ° C until selection. Results: Blood of 802 men (53.6%) and 695 women (46.4%) gave 61.85% S. typhi (n = 926), 31.26% S. Para typhi-A (n = 468) and 6, 88% S. Para typhi. n = 103) insulation. Broad agglutinins were detected in 473 (31.5%) of these people. Without detectable "O" antibodies, 1:80 "H" titers (n = 264: 17.6%) were most commonly observed in children's sera (n = 112; 7.4%). Widal H with agglutinin "O" was recorded in 209 (13.9%) corresponding positive blood cultures, and 104 (6.9%) gave a titre of 1: 320 or more. A total of 1,024 sera (58.4%) did not have detectable Widal antibody. Typhidot immunoglobulin spots (57.1%), negative in 856 sera, were detected in 641 samples (42.8%). IgG-free IgM stains without detectable IgM, IgG stains without IgG were also observed in 22 sera (1.47%) and samples producing S. Para typhi-A isolate (n = 8) and S. Para typhi-B. Conclusion: S. Para typhi-A has often grown in the last decade, suggesting incomplete protective coverage, probably with a monovalent vaccine. Antibodies against Widal and Typhidot agglutinins were detected in the serum of patients with Salmonella growing in blood in 31.5% and 42.8%, respectively. Widal may be misinterpreted because of possible "lower" agglutinins that have not been inoculated, and the EIA immunoassay is particularly limited only to S. typhi. An ICT based Salmonella serotype three indicator is desirable.

Background: Typhoid is mainly a disease of developing country, and inappropriately treated most of time due to lack of highly skilled diagnostic tools specially at primary level. So to validate most easy and rapid investigation Typhidot EIA with nested PCR may prove quite necessary due to low yield of culture reports. Aims: The objective was to evaluate the clinical profile and immediate diagnostic tool typhidot considering nested PCR as gold standard due to it’s high sensitivity and specificity rates. Material and Methods: Clinical profile of 100 case of provisional enteric fever recorded along with amplification of The DNA fragment of flagellin (H1-d) and stkG gene for salmonella typhi and salmonella paratyphi A respectively by nested PCR done in blood clot,unine and stool sample, along with blood clot culture,urine and stool culture done. Further validation of ELISA card test i.e. typhidot EIA done considering nested PCR as gold standard, for validation of test control group consisted of 40 health subjects. Results: Nested PCR which showed overall 84% positivity. Total Culture positivity was 60 among all samples and among that Clot culture 35(35%),urine culture 3(3%)and stool culture yield was 22(22%) respectively .Validation of Typhipoint EIA IgM showed 92.8% sensitivity and 68.7% specificity. Conclusion: It may be advised that 2-3 specific antigens of S. Typhi are spotted on the membrane and ELISA based detection should be carried out to reach the satisfactory level of diagnosis of enteric fever in field condition for more accuracy in rapid test to avoid inappropriate antimicrobial therapy and costly investigations. Funding Statement: None. Declaration of Interests: None. Ethics Approval Statement: The study was conducted as a part of dissertation in collaboration with department of general medicine and department of microbiology at I.M.S , B.H.U Varanasi. The well informed consent was taken from each of the participants and the study plan was approved by the Institute Ethics Committee.

Introduction: Enteric fever is a global health problem and is also endemic in India. The laboratory diagnosis of enteric fever is very important mainly because in post-antibiotic era most cases are treated empirically and investigated for various causes of PUO including enteric fever. A fast, reliable, and easy to perform serodiagnostic test with a higher sensitivity and specificity is required for rapid diagnosis and management of typhoid cases, thereby enabling clinicians to initiate an early therapy, reducing morbidity and its complications. Aim : The study was performed to evaluate the performance of Widal test and Typhidot, a lateral flow immunoassay test. Materials and Methods: This study was carried out in the Department of Microbiology in a tertiary care center for 1 year (August 2016– July2017). A total of 110 blood samples were collected from patients (cases) clinically suspected of enteric fever. Culture and Serological tests were done in all the 110 cases. Salmonella isolation was done by conventional methods of culture. Demonstration of presence of anitibodies were done by Widal tests using commercially available kits. Typhidot, a lateral flow immunoassay, was used to test and detect IgM and IgG antibodies against the outer membrane protein (OMP) of the Salmonella Typhi. The performances of the tests were compared, and diagnostic accuracy determined. Results : Out of 110 cases, highest percentage of positive cases were found by Typhidot test (29.09%) followed by Widal test (23.63%) . 18.18% cases were confirmed by blood culture. Taking blood culture as gold standard , it was found that Widal test had a sensitivity of 30% and specificity of 78% and Typhidot had a sensitivity of 75% and specificity of 81%. Conclusion : Though definitive diagnosis of enteric fever is isolation of the causative organism from the patient, Widal test and Typhidot test are important diagnostic tools in the medical set up. Typhidot is fast becoming a practical alternative to Widal test. Typhidot test had a fairly good sensitivity and specificity, whereas Widal test had good specificity but a lower sensitivity.

Introduction: Widal test has been used extensively for the sero-diagnosis of Enteric fever in India, however, its accuracy and reliability are debatable. We studied widal testing and widal positivity rates in the entire city of Ahmedabad for the diagnosis of Enteric Fever. Methods We screened all 1700 possible diagnostic laboratory facilities, in Ahmedabad, in the public and private sector. We performed telephonic surveys for the initial filtering of facilities that could be conducting widal testing. It was followed by physical visits to probable facilities to confirm testing methods and preservation of reports of widal testing. We followed a systematic process for screening and selection of 23 laboratories, which conducted widal tests and had reliable data. While 14 laboratories refused to share data, data provided by three of them were inappropriate and couldn’t be used. We finally analyzed data from four large public hospitals, one private trust hospital and one corporate laboratory for variable periods in a span of 15 years (2000 – 2015). Result: The Widal testing rate was found to be 8.7% and widal positivity as 12.5% in a sample of 1.2 million clinically suspected in-patients. In 15 years, the private hospital had admitted 1/10th as many cases as all the public hospitals together. However, the widal testing and positivity rates were similar in both. We observed a lower proportion of widal positivity among children below 12 years and a disproportionate, but insignificant, gender distribution of widal positivity. Conclusion: This study indicates that the widal test, which is meant to be an initial screening test, is widely used in the city. We propose linkage of testing and reporting of widal with other more reliable and accurate tests such as Typhidot and blood culture in order to strengthen our knowledge of enteric fever epidemiology in India.

Objective: To evaluate the diagnostic utility of Typhidot-M and Widal test in the early diagnosis of enteric fever (EF) in terms of sensitivity and specificity. Methods: The study included 270 children in the age group of 1-18 years admitted to the Department of Pediatrics from November 2012 to February 2014, with fever of 5 days or more and with clinical symptoms and signs suggestive of typhoid fever. Detailed history and clinical examination findings were recorded on a standard pro forma. Complete hemogram (hemoglobin, platelet count, and total and differential leukocyte count), Typhidot-M test, Widal tube test, and blood culture weredone on day 1 of admission. For Widal test, a titer of 1 in 160 or more for “O” agglutinins and a titer of 1 in 320 or more for “H” agglutinins were considered as positive results. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated. Results: Of 270 children included in the study, Salmonella typhi was isolated from 82 samples (30.4%) and the remaining 188 (69.6%) were blood culture negative. Widal test was positive in 107 children (39.6%) and Typhidot-M was positive in 136 (50.4%). The sensitivity was 78%, specificity was 79.3%, PPV was 59.8%, and NPV was 91.4% for Widal test. Typhidot-M test had a sensitivity of 81.7%, specificity of 84.6%, PPV of 69.8%, and NPV of 91.4%. Conclusion: Prompt diagnosisof EF is essential for appropriate management and it is, therefore, important to have a satisfactory test to replace conventional tests used for diagnosis. The present study compares newer test (Typhidot-M) against conventional tests such as Widal test and blood culture, and it appears to be a practical alternative to Widal test in the early detection of EF even in the resource-poor laboratories as it neither requires much laboratory equipment nor laboratory expertise to conduct the test. This test can be done within 7 days of illness, but whenever feasible confirmation with blood culture is strongly recommended, especially with the well-documented presence of multidrug-resistant strains of salmonella typhi worldwide. However, both Widal and Typhidot-M appear to correlate less satisfactorily with blood culture, and thus, there is a need for developing a test which allows accurate and early diagnosis of EF to manage a child effectively and limit its morbidity and mortality.

Introduction : Typhoid fever is a life threatening systemic infection that is usually presented with non- specific symptoms and signs . Its diagnosis is usually confirmed by blood culture and Widal test. The delayed results of microbiologic examination and the unreliable results of Widal test makes the search for a rapid and reliable method for diagnosis of typhoid fever. An early and accurate diagnosis is necessary for a prompt and effective treatment. The objectives were to compare the sensitivity and specificity of Widal test and typhidot with the blood culture in the diagnosis of typhoid fever in children. Material and Methods: A total of 200 hundred clinically suspected typhoid fever cases of 2-12 year age groups from both sexes attending Basaveshwara Medical College Hospital Chitradurga were studied. The blood collected aseptically was used for blood culture and clotted blood was used for Widal test and typhidot test. Results : Of 200 blood samples studied, 28 cases were positive by blood culture. Widal test showed sensitivity and specificity of 53% and 83% on blood culture proven cases. Typhidot test showed sensitivity and specificity of 93% and 83%, respectively on blood culture proven cases. Conclusion : Using blood culture as the gold standard, typhidot showed a higher sensitivity compared to Widal test. The specificity of both Widal and typhidot remained the same. Typhidot could be a practical alternative to Widal test in the diagnosis of typhoid fever even in the resource poor laboratories. J Nepal Paediatr Soc 2016;36(2):131-135.

Enteric fever is a common infectious disease, especially in countries with poor sanitation and in the tropics. It is caused mainly by Salmonella typhi and accounts for nearly 27 million cases worldwide and 200,000 deaths annually. Enteric fever involves the reticuloendothelial system such as bone marrow, spleen, and liver. As it mostly involves the Peyer’s patches of the terminal ileum, enteric perforation occurs commonly. However, gallbladder perforation can also occur, though not very often. Ultrasound as well as computerized tomography (CT) abdomen and pelvis lack specificity for detecting gallbladder perforations in enteric fever. Diagnosis is usually confirmed intraoperatively when the gallbladder is visualized and perforation is seen. Gallbladder perforation is usually seen in acute cholecystitis when the gallbladder becomes necrotic and gangrenous. In acalculous cholecystitis, perforation is rare. Enteric fever is one of the rarest causes of acalculous cholecystitis, leading to perforation. Here, we present the case of a 20-year-old man who presented with fever for 10 days along with loose stools, vomiting, and acute abdomen. Labs showed leukopenia, positive Typhidot test but X-ray erect abdomen and ultrasound abdomen and pelvis were nonspecific. Only after resuscitation and exploration of the abdomen was it found that the gallbladder had multiple perforations. The patient was improved after eight days of postoperative intravenous antibiotics. This is a unique and rare presentation of such a common infectious disease.

Background: Typhoid fever still continues to be a major public health problem in Nepal. A clinical spectrum of typhoid varies widely. It causes significant complication as well as mortality. A simple, reliable, affordable and rapid diagnostic test has been a long felt need of the clinicians to prescribe specific medication, adopt prevention of the emergence of antibiotics resistance and overall reduce the disease burden in the community.Methods: The prospective descriptive study was performed in 125 children between 2 years to 15 years of age admitted to the Pediatrics Department from September 2017 to September 2018. Blood culture, Typhidot rapid IgM were performed. MEDCALC software was used to calculate 95% confidence interval for sensitivity, specificity, predictive value positive, predictive value negative and accuracy. Kappa test was used to determine the agreement between Typhidot IgM and blood culture methods.Results: The study consisted of 125 children with acute febrile illness for more than 3 days with clinical symptomatology, consistent with typhoid fever. The reliability of Typhidot IgM in relation with blood culture and the study lighten that sensitivity 92.3% (95% CI: 63.9, 99.8), specificity 49.1% (95% CI: 39.5, 58.7), PPV 17.4% (95% CI: 14.2, 21.1), NPV 98.2% (95% CI: 89.2, 99.7) and accuracy 53.6% (95% CI: 44.5, 62.6). The two methods i.e. Typhoid IgM and blood culture shows significant agreement with p value 0.004.Conclusions: The present study demonstrates that Typhidot IgM has all the attributes of an ideal screening test.

Objective To find out frequency of various complications in children admitted with Enteric Fever at a tertiary care hospital. Methods This was prospective cross sectional study, carried out in the Pediatric Medicine department of The Children's Hospital Lahore from Dec 2014 to March 2017. Children of both genders with age range of 6 months to 16 years diagnosed as enteric fever on the basis of clinical features and positive Typhidot, or blood culture were included in the study. All 180 patients were scrutinized for all possible complications. Where ever required and feasible appropriate and relevant investigations were done to document complications. Data was analyzed by SPSS version 20. Results Mean age of children was 7.2±3.38, majority 94 (52.2%) were 5-10 years old. Out of 180 patients, complications were noted in 58 (32.2%). Neurological complications 30.7% encompassed maximum complications followed by hepatobiliary 24.61%, abdominal 16.92% hematological 9.23%, bone and joints 7.69%, respiratory system 6.1% and cardiovascular system 4.41%. Mortality rate was 1.6%. Thrombocytopenia and leucopenia were significantly associated with complications with p value of 0.002 and 0.003 respectively. Conclusion Enteric fever is causing our children to suffer by its numerous perplexing and fatal complications. The most vulnerable age for enteric fever and its complication is 5-10 years. To combat these issues large scale vaccination remains promising option at least in most susceptible age group.

Background There is a need for a reliable, simple diagnostic assay for typhoid fever. Available commercial serologic assays for typhoid fever have limited sensitivity and specificity. Using high-throughput immunoscreening technologies, we previously identified several immunoreactive Salmonella Typhi antigens that seem promising for possible inclusion in a new diagnostic assay: hemolysin E (HlyE), cytolethal distending toxin, S. Typhi lipopolysaccharide (LPS), and S. Typhi membrane preparation. Methods We assessed plasma antibody responses (immunoglobulin [Ig] M, IgA, and IgG) to these antigens by means of enzyme-linked immunosorbent assay in patients with suspected enteric fever, controls with other febrile illnesses, and healthy controls in Dhaka, Bangladesh and performed Tubex and Typhidot tests, the Widal assay, and the typhoid/paratyphoid test (TPTest) in each patient. Using machine learning methods, we identified a parsimonious serology signature to distinguish acute typhoid cases from controls and then validated our findings in an independent test cohort from Nepal of patients with culture-confirmed S. Typhi and controls with other bacteremic illnesses. Results We demonstrated that the use of 2 antigens (HlyE and LPS) with 1 antibody isotype (IgA) could distinguish typhoid from other invasive bacterial infections (area under the receiver operating characteristic curve [AUC], 0.95; sensitivity, 90%, specificity, 92%). Use of a single antigen (HlyE) and isotype (IgA) had an AUC of 0.93. Conclusion Our results suggest that development of a diagnostic assay for acute typhoid fever focused on detecting IgA responses against HlyE, with or without LPS, is warranted., Using machine learning methods, we identified and validated anti–hemolysin E immunoglobulin A and antilipopolysaccharide immunoglobulin A plasma responses as predictors of acute typhoid fever in 2 independent cohorts of patients in Bangladesh and Nepal (sensitivity, 90%; specificity, 92%).

Objective To analyse seropositivity rates of salmonella with seasonal variations in the population of Taxila and the surrounding rural areas. Methods The study was conducted among 760 suspected patients with symptoms of fever, headache, nausea and decreased white blood cells count screened for the typhoid fever. Blood samples collected from the suspected patients were tested for seropositivity by slide agglutination (Widal test) and Immunochromatographic test, i.e . Typhidot. Results From overall 760 suspected patients of typhoid fever only 192 (25.26%) samples were positive for Widal and Typhidot test. The peak seropositivity rates were identified during the months of April–June, while decreased cases were observed from January to March. Age wise distribution of typhoid fever reflected that age groups of 10–15 years and 25–35 years were at higher risks of developing enteric fever with respect to age groups of 5–10 years and 61–70 years, respectively. On gender basis evaluation, females (24.49%) were slightly at low risks of developing typhoid fever than males (25.9%). Conclusions The present study highlights a higher burden of typhoid fever in Taxila and the surrounding areas population that directly reflects the poor hygienic condition and contamination of drinking water. The frequency of typhoid fever fluctuates with seasonal variations as higher rates found during the summer as compared to winter season.

Typhoid and Dengue both are so different diseases but they have some similar routine manifestations like fever. Our 6 months performed study was to determined contemporaneous infection of both diseases having same routine manifestations in patients at the same period of time. We were collected the blood samples from suspected patients. The serum were separated out through centrifugation from the desired blood samples and tested for typhoid by Rapid Immuno-chromatographic (typhidot) technique and for the dengue we performed NS1 Rapid technique. The performed results showed that 64.4% typhoid positive from dengue negative patients and 4% dengue positive from typhoid negative patients but we were not found any suspected patient who infected with both diseases at the same time. From our performed results we can conclude that the contemporaneous infections should be confirmed by diagnostic laboratory properly because it may leads to misdiagnosis and creates difficulties to the physician for their respective treatments. To restraint the contagious infections we should prevent the route of infections because prevention is better than cure.

Aims: The aim of the study was to evaluate the effect of the standardized ethanolic extract of Andrographis serpyllifolia leaves on experimentally induced typhoid. Study Design: Single dose of 1 ml Salmonella Typhi (10 CFU/mL) was administered orally to rats to induce typhoid in rats. Blood culture test confirmed typhoid infectioned rats received orally the ethanolic extract of Andrographis serpyllifolia at dose levels of 200 and 400 mg/kg twice daily for 10 days, respectively and control animals received physiological saline. Place and Duration of Study: CSIR-National Botanical Research Institute (NBRI), Lucknow, between December 2011 and June 2013. Methodology: Leaves of Andrographis serpyllifolia was extracted with ethanol and concentrated on rotavapour. Single dose of 1 ml S. Typhi (10 CFU/mL) was administered orally to rats with the help of orogastric tube to induce typhoid in rats. After seven days, Original Research Article British Journal of Pharmaceutical Research, 4(2): 230-239, 2014 231 typhoid confirmed rats received the standardized extract subsequently subjected to in vitro antimicrobial susceptibility test. Results: The treatment with ethanolic extract of Andrographis serpyllifolia at dose level of 200 mg/kg showed 75.0% to 87.5% protection and 100% protection observed at higher dose of 400 mg/kg on widal, blood culture and typhidot test respectively. Biochemical test carried out on blood culture isolates confirmed the presence or absence of S. Typhi. A. serpyllifolia extract at a concentration of 1.50 mg/disc showed antimicrobial activity susceptibility against S. Typhi. Conclusion: Andrographis serpyllifolia leaves extract showed antimicrobial activity against S. Typhi and accomplished the extract of A. serpyllifolia is recommended for clinical applications in the treatment of typhoid.

Background Typhoid fevers are infections caused by the bacteria Salmonella enterica serovar Typhi (Salmonella Typhi) and Paratyphi A, B and C (Salmonella Paratyphi). Approximately 17.8 million incident cases of typhoid fever occur annually, and incidence is highest in children. The accuracy of current diagnostic tests of typhoid fever is poorly understood. We aimed to determine the comparative accuracy of available tests for the pediatric population. Methods We first conducted a systematic literature review to identify studies that compared diagnostic tests for typhoid fever in children (aged ≤15 years) to blood culture results. We applied a Bayesian latent-class extension to a network meta-analysis model. We modelled known diagnostic properties of bone marrow culture and the relationship between bone marrow and blood culture as informative priors in a Bayesian framework. We tested sensitivities for the proportion of negative blood samples that were false as well as bone marrow sensitivity and specificity. Results We found 510 comparisons from 196 studies and 57 specific to the pediatric population. IgM-based tests outperformed their IgG-based counterparts for ELISA and Typhidot tests. The lateral flow IgG test performed comparatively well with 92% sensitivity (72% to 98% across scenario analyses) and 94% specificity. The most sensitive test of those investigated for the South Asian pediatric population was the Reverse Passive Hemagglutination Assay with 99% sensitivity (98% - 100% across scenario analyses). Adding a Widal slide test to other typhoid diagnostics did not substantially improve diagnostic performance beyond the single test alone, however, a lateral flow-based IgG rapid test combined with the typhoid/paratyphoid (TPT) assay yielded improvements in sensitivity without substantial declines in specificity and was the best performing combination test in this setting. Conclusion In the pediatric population, lateral-flow IgG, TPT and Reverse Passive Hemagglutination tests had high diagnostic accuracy compared to other diagnostics. Combinations of tests may provide a feasible option to increase diagnostic sensitivity. South Asia has the most informed set of data on typhoid diagnostic testing accuracy, and the evidence base in other important regions needs to be expanded., Author summary Typhoid fever is an infection caused by the bacterium Salmonella Typhi. Typhoid fever is rare in developed countries but remains high in the developing world. Effective treatment is available but accurate diagnosis of typhoid fever is challenging as typhoid fever can be difficult to distinguish from other infections. Bone marrow culture is the most accurate diagnostic test for typhoid fever however is invasive and not feasible in many settings. New vaccines for typhoid and the need for improved estimates of burden increases the demand for improved understanding of diagnostic accuracy. Comparing the diagnostic accuracy of tests for typhoid fever is challenging as head-to-head studies are few. We applied newly developed methods for comparative evaluation of diagnostic tests for typhoid fever in children using statistical approaches that allowed for the proper incorporation of uncertainty and comparison of tests that had not been compared directly. The lateral-flow IgG, TPT and Reverse Passive Hemagglutination tests all had good diagnostic accuracy compared to other diagnostics. Combinations of tests may provide a feasible option to increase diagnostic sensitivity. Finally, while South Asia has the most informed set of data on typhoid diagnostic testing accuracy, the evidence base in other important regions needs to be expanded.

AIM AND OBJECTIVES: Purpose of the study is to compare the sensitivity and specificity of Widal test and Typhi dot with the blood culture, in the diagnosis of Typhoid fever. Material and methods:- Blood samples from 200 clinically diagnosed typhoid cases, were subjected to blood culture and the isolates were identified by biochemical reactions and samples were subjected to serological tests, Widal test and Typhi dot test. RESULTS: Out of 200 clinically diagnosed typhoid cases, 28 (14%) were blood culture positive for Salmonella typhi, 43 (21.5%) were Widal positive and 55 (27.5%) were Typhi dot positive. CONCLUSION : Blood culture and Widal test are used as conventional methods in the diagnosis of the typhoid fever. Typhi dot test is a new rapid serological test introduced commercially for the diagnosis typhoid fever. Typhi dot test has been designed to detect the IgM and IgG antibodies against the outer membrane protein (OMP) of Salmonella typhi. It offers the advantage of rapid & early diagnosis, with a sensitivity & specificity of 92% & 83% respectively in culture proven cases.

Objectives: To determine the seropositivity of typhoid fever in febrile pediatric patients presenting to tertiary care center. Methods: This observational study was conducted at Children Hospital Quetta (CHQ) from July 2011 to March 2012. The children with three or more days fever, no obvious focus of infection and clinically suspected of typhoid fever were screened. Sterile Blood samples were obtained from febrile patients and Widal and Typhidot® tests were performed for the diagnosis of Typhoid fever in the suspected populations. Results: Total of 2964 clinically suspected patients were screened for typhoid fever. Of these, 550 (18.6%) patients were positive serologically. The higher prevalence of the disease in hot summer season and increasing pattern of the disease was observed in summer days. The disease was higher in school age children under 5-10 years. Although non-significant association was observed on sex basis. Conclusion: The findings highlight the considerable burden of typhoid fever in pre-school and school-aged children. The variation in the disease pattern has also been observed under seasonal variation and different age groups, all of which need to be considered in deliberations to control the typhoid fever.

Enteric fever is still regarded as a major public health problem globally. Worldwide there were an estimated 22 million cases of enteric fever, with 2,00,000 deaths in 2002. The incidence is highest (>100 cases per 1,00,000 population per year) in South Central and South East Asia. It is estimated that there is one case of paratyphoid fever for every four cases of typhoid fever, but the incidence of infection associated with S paratyphi A appears to be increasing, especially in India. In this issue Gupta et al [1], from Bangalore report that 20% of their 81 cases of culture positive Enteric fever were due to S paratyphi. Another study of 119 culture positive cases from Mumbai shows that 39% of their cases were of S paratyphi infection [2]. Traditionally, it has been believed that enteric fever has a lower incidence and a benign course in preschool children. However, recent population based studies in South Asia show that the incidence is highest in children less than five years of age with higher rates of complications and hospitalization [3]. Enteric fever is a potentially lethal disease but its course can be altered favourably if appropriate antibiotics are exhibited early in the illness. However, given the non specific nature of presentation there are no discerning clinical clues which aid the physician. One can only resort to a high index of suspicion. In the tropics, the presentation is indistinguishable from malaria, viral hepatitis, bacterial enteritis, dengue, rickettsial fever, leptospirosis and amoebic liver abscess. Given the name Enteric Fever, one would expect an illness dominated by gastro intestinal manifestations. However, abdominal pain (30-40%), vomiting (18%), diarrhea (22-28%) and constipation (13-16%) do not constitute the hall mark features of the disease [4]. Constipation was not encountered at all in the Mumbai series of 119 cases [2]. The oft quoted relative bradycardia is an inconsistent finding [2, 3]. However, two thirds of the 81 cases reported in this issue by Gupta et al [1], had relative bradycardia. The classic mode of presentation with a slow and “step ladder” rise in fever is seldom seen and “Rose Red” spots are elusive in Asians. The incidence of splenomegaly is variably quoted. The Kathmandu group found splenomegaly in 5-6% of their 669 cases while the Mumbai study encountered splenomegaly alone or as part of hepatosplenomegaly in 20% of the cases [2, 4]. Gupta et al [1], however report a much higher occurrence of splenomegaly to the tune of almost 60%. It can well be concluded that there is nothing typical about the presentation of enteric fever and the threshold for considering the diagnosis has to be low. To make matters worse, a “hepatitic” presentation may be encountered in 4.8 to 8.6% of the cases [5]. How far does the laboratory come to the rescue? Leucopenia or a normal leucocyte count is the norm in enteric fever but leucocytosis is common in children and in those with complications. However, the presence of leucocytosis casts a doubt on the diagnosis of typhoid fever. Leucocytosis was seen only in 4 out of 119 culture positive cases of the Mumbai study [2]. The same study found absolute eosinopenia (AEC=0) in 77% of the cases and the authors propose this to be a useful marker of enteric fever. The Widal test lacks sensitivity and specificity and at best is a rough screening tool. The “Gold Standard” for diagnosis is culture positivity. The Mumbai study [2], found cultures positive in 52.6% of their cases in whom “Enteric Fever” was the diagnosis at discharge. It was heartening to observe that a substantial (46.2%) number of cases which were culture positive had received prior antibiotics. Therefore, antecedent antibiotic therapy should not dissuade a physician from sending cultures. Bone marrow cultures are said to retain a high sensitivity (90%) despite antibiotic therapy but the obvious constraints are that the test is invasive and more applicable to the hospital setting. Culture of intestinal secretions (best obtained by a non invasive duodenal string test) can be positive despite a negative bone marrow culture [6]. It would be interesting to extrapolate this to endoscopically obtained duodenal secretions at least in the centers where endoscopy is available and see if a relatively non invasive method for culture becomes available. Newer serological diagnostic techniques such as Typhidot, Typhidot M and Tubex detect the IgM response and are stated to have good sensitivity and specificity but have not proved to be robust enough in the community setting [3]. A high incidence of nalidixic acid resistant Salmonella typhi (NARST) isolates is reported in the study by Gupta et al [1] and the study by Jog et al [2], viz 86% and 79% respectively. In therapeutic terms, this portends fluoroquinolone resistance. Fortunately, resistance to third generation cephalosporins is not an issue at present, though a substantial relapse rate with ceftriaxone is an area of concern. Oral azithromycin is an exciting prospect that gives cure rates which are better than quinolones and comparable to ceftriaxone, with the added advantage of lower relapse rates [7]. Salmonella infection has challenged physicians since the times of Aristotle and still continues to do so today. Diagnosis can be elusive since the disease can be protean in its manifestations. The third world physician would do well to consider enteric fever in all the short term febrile illnesses that he encounters. Multidrug resistance is an area of concern but thankfully the pharmacological armamentarium has kept pace. Above all, it is the early exhibition of an appropriate antibiotic which will salvage many a patient.

Background There is an urgent need for an improved diagnostic assay for typhoid fever. In this current study, we compared the recently developed TPTest (Typhoid and Paratyphoid Test) with the Widal test, blood culture, and two commonly used commercially available kits, Tubex and Typhidot. Methodology For analysis, we categorized 92 Bangladeshi patients with suspected enteric fever into four groups: S. Typhi bacteremic patients (n = 28); patients with a fourfold change in Widal test from day 0 to convalescent period (n = 7); patients with Widal titer ≥1:320 (n = 13) at either acute or convalescent stage of disease; and patients suspected with enteric fever, but with a negative blood culture and Widal titer (n = 44). We also tested healthy endemic zone controls (n = 20) and Bangladeshi patients with other febrile illnesses (n = 15). Sample size was based on convenience to facilitate preliminary analysis. Principle findings Of 28 S. Typhi bacteremic patients, 28 (100%), 21 (75%) and 18 (64%) patients were positive by TPTest, Tubex and Typhidot, respectively. In healthy endemic zone controls, the TPTest method was negative in all, whereas Tubex and Typhidot were positive in 3 (15%) and 5 (25%), respectively. We then estimated sensitivity and specificity of all diagnostic tests using Bayesian latent class modeling. The sensitivity of TPTest, Tubex and Typhidot were estimated at 96.0% (95% CI: 87.1%-99.8%), 60.2% (95% CI: 49.3%-71.2%), and 59.6% (95% CI: 50.1%-69.3%), respectively. Specificity was estimated at 96.6% (90.7%-99.2%) for TPTest, 89.9% (79.6%-96.8%) for Tubex, and 80.0% (67.7%-89.7%) for Typhidot. Conclusion These results suggest that the TPTest is highly sensitive and specific in diagnosing individuals with typhoid fever in a typhoid endemic setting, outperforming currently available and commonly used alternatives., Author Summary We compared the performance of the recently developed TPTest (Typhoid and Paratyphoid Test) with the Widal test, blood culture, and commercially available kits, Tubex and Typhidot in diagnosing the patients with typhoid fever. There is no acceptable gold standard; therefore, we estimated the sensitivity and specificity of these diagnostic methods with Bayesian latent class modeling. We found that the sensitivity and specificity of the TPTest is higher than other commonly used methods for diagnosis of typhoid fever.

Typhoid fever remains a major global health problem. A major impediment to improving outcomes is the lack of appropriate diagnostic tools, which have not significantly improved in low-income settings for 100 years. We evaluated two commercially available rapid diagnostic tests (Tubex and TyphiDot), a prototype (TyphiRapid TR-02), and the commonly used single-serum Widal test in a previously reported high-burden area of Papua New Guinea. Samples were collected from 530 outpatients with axillary temperatures of ≥37.5°C, and analysis was conducted on all malaria-negative samples (n= 500). A composite reference standard of blood culture and PCR was used, by which 47 participants (9.4%) were considered typhoid fever positive. The sensitivity and specificity of the Tubex (51.1% and 88.3%, respectively) and TyphiDot (70.0% and 80.1%, respectively) tests were not high enough to warrant their ongoing use in this setting; however, the sensitivity and specificity for the TR-02 prototype were promising (89.4% and 85.0%, respectively). An axillary temperature of ≥38.5°C correlated with typhoid fever (P= 0.014). With an appropriate diagnostic test, conducting typhoid fever diagnosis only on patients with high-grade fever could dramatically decrease the costs associated with diagnosis while having no detrimental impact on the ability to accurately diagnose the illness.

Background: Typhoid fever is widely recognized as a major public health problem in developing countries. A simple, reliable and rapid diagnostic test is needed for clinicians especially in areas where laboratory services are limited. Objective: To evaluate sensitivity and specificity of typhidot (IgM), a serological test to identify IgM antibodies against salmonella typhi. Study Design: This was a prospective study. Setting: Northern Institute of Medical Sciences (NIMS) and Ayub Teaching Hospital Abbottabad. Period: 1st November 2009 to 31st August 2010. Methods: A total of 100 patients with clinically suspected typhoid fever were studied and divided into three main groups as A, B and C, with definite typhoid fever, typhoid suspects plus non-typhoidal illnesses and healthy controls respectively. Blood culture and typhidot (IgM) tests were conducted for all subjects included in the study. The validity of typhidot (IgM) test has been evaluated by determining the sensitivity, specificity, positive and negative predictive values. Results: In our study, majority (75%) were males and (25%) females with M to F ratio of 3:1. The mean age of study group was 26.31±11.8 (SD) years. Among 100 clinically diagnosed typhoid fever patients, 19 had positive blood culture for S.typhi and 71 were typhidot (IgM) positive. Out of 19 culture positive patients, 18 (94.73%) were true typhidot (IgM) positive, which was also falsely positive in 05 (20.83%) among 24 non- typhoidal febrile controls. None of the healthy controls was positive for typhoid (IgM) test. The sensitivity, specificity, negative and positive predictive values of typhidot (IgM) test using blood culture as gold standard were 94.73%, 90%, 97.72% and 78.26% respectively for patients having typhoid fever. Conclusions: Typhidot (IgM) test is a simple, reliable, rapid and valid diagnostic tool for typhoid fever especially in areas where laboratory services are limited.

Background: The often-non-specific presentation of typhoid fever makes clinical diagnosis difficult. The blood culture is time consuming, affected by often given prior antibiotics and has low sensitivity (60%). Typhidot IgM gives quick results in early stage of disease. Pediatric data are scarce. So, we studied and compare Typhidot IgM test and blood culture in children with clinically compatible enteric fever.Methods: This was retrospective observational study done in Department of Pediatrics from the 1st October, 2017 to 30 September, 2018. 42 children with clinically compatible enteric fever (aged 6 months to 18 years); with either typhidot IgM or blood culture positive for Salmonella species were sampled and analyzed.Results: Typhidot IgM test had sensitivity of 92.7% (N = 39/42) compared to blood culture with sensitivity of 79.4% (N = 27/34). 2 out of 3 typhidot negative cases were S. Paratyphi positive in blood culture. Typhidot IgM had positive predictive value = 97.4% due to 1 false positive case. 19 (79.2%) out of 24 blood culture positive patients had not received any antibiotic prior test, 3 (60 %) out of 5 blood culture negative patients had received antibiotics.Conclusions: Typhidot IgM is a highly sensitive quick diagnostic tool for diagnosing enteric fever in children with sensitivity of 92.3% and PPV of 97.4% compared to blood culture (sensitivity= 79.4%). It is more sensitive to diagnose S. typhi enteric fever (sensitivity= 97.3%) then S. paratyphi (sensitivity= 50%). Antibiotic administration prior to blood culture testing reduces its positivity rate but not significantly statistically. Larger studies are needed to change the current recommendations on typhidot IgM.

Typhoid fever still continues to be a major public health problem, particularly in many 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. The study was carried out in the department of Microbiology, Mymensingh Medical College, Mymensingh between June, 2006 and July, 2007, on a total of 100 samples from clinically suspected patients to have typhoid fever. Blood culture as well as Typhidot test were performed for each of the cases. Out of 100 clinically diagnosed typhoid fever, 14 were blood culture positive for S. typhi and 73 were Typhidot (IgM) positive. Among 14 culture positive cases, 13 (92.85%) were Typhidot (IgM) positive. The test was also positive in 04 (20%) out of 20 febrile controls. None of the healthy controls was positive by Typhidot (IgM). The sensitivity, specificity, positive predictive value and negative predictive value of the test using blood culture as gold standard were 92.85%, 90.00%, 76.47% and 97.29% respectively for typhoid fever. Typhidot (IgM) test is rapid, easy to perform and reliable test for diagnosing typhoid fever, and useful for small, less equipped laboratories as well as for the laboratories with better facilities. Key words: Typhoid fever, Salmonella typhi, Typhidot (IgM) test doi: 10.3329/bjmm.v3i1.2964 Bangladesh J Med Microbiol 2009; 03 (01): 10-13

Tubex and Typhidot, rapid tests for typhoid fever, performed well in evaluations conducted in hospital settings among patients with culture-confirmed typhoid fever. We evaluated these tests in a community clinic in Bangladesh. Blood samples were obtained from 867 febrile patients for culture, Typhidot and Tubex tests. Considering the 43 blood culture-confirmed cases of typhoid fever as typhoid positive and the 24 other confirmed bacteremia cases as typhoid negative, Tubex was 60% sensitive and 58% specific, with 90% positive and 58% negative predictive values (NPVs); Typhidot was 67% sensitive and 54% specific, with 85% positive and 81% NPVs. When blood culture-negative patients and other bacteremia cases together were considered typhoid negative, positive predictive values were only 14% for Tubex and 13% for Typhidot, increasing to only 38% and 20% when restricted to patients with > or = 7 days of fever. We conclude that the value of Tubex and Typhidot tests for typhoid fever diagnosis in a community clinic in urban Bangladesh is low.