The accuracy of widal test for typhoid fever diagnosis in Ethiopia: Systematic review and meta-analysis

Introduction: Widal agglutination test is a serologic investigation that is used to diagnose typhoidfever. This is an easy, fairly inexpensive, and readily available test it'ith questionable reliability. The test performance differs from setting to setting depending on the technique used and otherfactors. The accuracy ofthis test in Ethiopia is poorly understood. So, the aim of this scientific work was to analyze the accuracy of Widal agglutination in diagnosing typhoidfever in Ethiopia. Methods: We performed a systematic review and meta-analysis. Two electronic databases (PubMed/Medline and Google scholar) were searched using preset search strategv to find relevant studies. The methodological quality of the studies included was evaluated "'ith a QUADAS-2. We extracted important variables from the eligible articles. Statistical analysis was conducted using STATA version 14. The protocol of our systematic review and metaanalysis is registered in the International Prospective Register of Systematic Reviews (PROSPERO) with the record number CRD42020194252. Results: The electronic quests yielded 42 papers of which 8 "'ere eligible for analysis. The quality of these studies was rated to be moderate based on the QUADAS-2. The pooled sensitivity, specificity, and negative, andpositive predicthe values ofthe Widal test were 80.8%, 53.0%, 98.5%, and 2.1% respecth'ely. Conclusion: The "'idal agglutination test has average specificity, ven good negative predicth'e value, and ven poor positive predictive value for the diagnosis of typhoidfever. Depending on Widal to diagnose typhoid fever may lead to over-diagnosis of typhoid fever and related complications including inappropriate use of antibiotics. There is an urgent needfor quick and dependable tests for diagnosing typhoidfever, particularly in settings like Ethiopia M'here doing timely culture is notfeasible.

Molecular diagnostics and next-generation sequencing reveal real etiological characteristics of invasive Salmonella infection in febrile illness in Freetown, Sierra Leone.

Invasive Salmonella infection, which can cause typhoid/paratyphoid fever and invasive non-typhoidal salmonellosis, is a public health burden in Africa. Accurate diagnosis and etiological characterization are required to conduct prevalence and risk estimations for Salmonella infection; however, the utilization of optimal techniques and surveillance data are still insufficient. In this study, we performed a laboratory-based survey in Freetown, which is the biggest city in Sierra Leone with a high burden of typhoid fever, by using blood culture and molecular methods but not the Widal test, to estimate the prevalence and aetiology of invasive Salmonella infection among fever patients. We found a very low prevalence of typhoid fever in patients with fever during the investigation period, and this prevalence was clearly overestimated by the Widal test. Genome sequencing of the S. Typhi isolate from this work revealed that the strain carried multiple antibiotic resistance genes, and an epidemic clone that has existed in West Africa for years was also detected in Sierra Leone. By using metagenomic sequencing, one patient with invasive non-typhoidal salmonellosis was identified as having bacterial co-infections. Our data highlight that Salmonella surveillance based on accurate laboratory diagnosis and genome sequencing needs to be strengthened to provide a better estimation of the real epidemics and enable potential risk assessment by etiological analysis in Africa. Even in a laboratory with only basic equipment, it is possible to conduct next-generation sequencing for pathogen discovery in bloodstream infections and to determine the etiological characteristics of pathogene without complex combinations of laboratory methods.

Traditional Widal Agglutination Test Versus Rapid Immunochromatographic Test in the Diagnosis of Enteric Fever: A Prospective Study From South India.

Introduction Early diagnosis and treatment are crucial to reducing the morbidity of patients with enteric fever/typhoid fever. Among the available diagnostic tests, the blood culture is considered a gold standard. However, in most of the developing and resource-limited settings, the diagnosis is made utilizing the traditional Widal test and rapid immunochromatographic test (ICT). This study was aimed to compare the diagnostic value and efficacy of ICT and traditional Widal test in the diagnosis of typhoid fever. Methods A prospective study was conducted, and 40 patients were included in the study. The Widal test and Salmonella enterica serovar Typhi IgM/IgG immunochromatographic test were performed for all the patients. The Widal is a tube agglutination test, and the rapid ICT utilizes the principle of enzyme-linked immunosorbent assay (ELISA). All the samples were also tested for the presence of antibodies (IgG and IgM) against the S. enterica serovar Typhi and the titers against 'O' and 'H' antigens of S. enterica serovar Typhi. An antibody titer of 1:80 or more against the 'O' and 'H' antigen was considered positive. Results In the ICT, 24 samples (60%) tested positive for the IgM antibodies, and only 15 samples tested positive and for IgG antibodies. In the Widal test, 27 samples (67.6%) returned positive for antibodies against the S. enterica serovar Typhi 'O' antigen. The sensitivity (90% vs 72.73%), specificity (81.25% vs 64%), and accuracy (82.12% vs 64.87%) for the Widal test were found to be more when compared to the ICT. Conclusion The results indicate that the traditional Widal agglutination test is superior to the rapid ICT in the diagnosis of enteric fever. However, both these tests cannot be considered as gold standards for the diagnosis owing to their low positive predictive values.

Estimation of Baseline Widal Antibody Titers among Apparently Healthy Urban Population of District Jammu.

INTRODUCTION: Definitive diagnosis of Enteric fever is by blood culture for Salmonella enterica serotype Typhi, Paratyphi A, and Paratyphi B which takes long turnaround time and is costly, whereas Widal test is simple, rapid, and cost-effective test whose interpretation depends on the baseline Widal titers among healthy individuals in a defined population. OBJECTIVES: To determine the baseline Widal titers among apparently healthy urban population of district Jammu (J&K). MATERIALS AND METHODS: 302 individuals in the age group of 18-50 years were recruited. A pretested questionnaire was used to collect demographic and clinical details. The Widal testing was done using commercial Salmonella antigen kit. RESULTS: A total of 302 samples were screened by Widal test. 138 samples (45.69%) were reactive for TO antigen and 64 (21.19%) tested reactive for TH antigen, 3 (0.01%) samples showed agglutination for AH antigen and 3 (0.01%) were positive for BH antigen. Majority of seropositive samples were in dilutions of 1:40 for both TO and TH antigens. CONCLUSIONS: Hence, next higher dilutions showing positivity for both TO and TH antigens, i.e., ≥1:80 may be considered diagnostic for enteric fever in the urban population of Jammu district.

Roles of Salmonella typhi and Salmonella paratyphi in Gallbladder Cancer Development.

BACKGROUND: Typhoid (Salmonella typhi and paratyphi) carriers and gall bladder cancer (GBC) are endemic in northern India. Results of previous studies about association of typhoid carriers with GBC are inconsistent. We studied antibodies against Salmonella typhi and paratyphi in serum samples of patients with GBC. METHODS: We performed modified Widal test for antibodies against Salmonella typhi (Vi and O) and Salmonella paratyphi (AO and BO) antigens in patients with GBC (n=100), xanthogranulomatous cholecystitis (XGC, n=24), chronic cholecystitis (CC, n=200) and healthy controls (HC, n=200). RESULTS: Serum antibodies against Salmonella were more frequently positive in GBC (22%) and XGC (29%), particularly in males in age ≥50 years (GBC: 47% and XGC: 50%) vs. HC (0) (p <0.01). Vi antibody was more common in GBC (13%, OR:9.8) and XGC (8%, OR:5.9) than HC (2%). O antibody was more common in GBC (8%, OR: 8.6) and XGC (8%, OR: 9.0) than HC (1%). O antibody was also more common in males with GBC (12%) than CC (1%) and HC (1%) (P=0.02 and p <0.001, respectively). AO (6%) and BO (4%) antibodies were detected in GBC, particularly in males, than HC (0), (p <0.01). Salmonella antibodies were more frequent in GBC with GS than those without GS (50% vs. 20%, OR=3.94, P=0.01). CONCLUSIONS: Salmonella carrier state was more common in GBC and XGC, particularly in elderly males than HC. The Vi antibody was more common in GBC and XGC than HC. Salmonella infection was more common in GBC with GS than those without GS.

Clinical Profile and the Role of Rapid Serological Tests: Typhifast IgM and Enterocheck WB in the Diagnosis of Typhoid Fever.

INTRODUCTION: During identification and diagnosis, typhoid fever (TF) causes various issues such as nonspecific symptoms and nontyphoidal Salmonella-associated febrile diseases. Accurate identification and diagnosis are still a substantial concern. The current study was undertaken to study the clinical profile of TF and the role of Typhifast IgM and Enterocheck WB in early diagnosis. MATERIALS AND METHODS: Clinically suspected TF patients (121) were included in the study. Patients with antibiotic history during the period of febrile illness were excluded. The diagnosis was confirmed with blood culture test. Widal test and two new rapid serological tests: Typhifast IgM and Enterocheck WB were performed. The outcomes were compared with blood culture-confirmed cases to derive the sensitivity and specificity of the diagnostic tests. The clinical characteristics were compared with diagnostic tests using Chi-square test. RESULTS: The most common presentations of TF were fever, chills, vomiting, abdominal pain, anorexia, constipation, and diarrhea. Among the 121 clinically suspected TF patients, 67 had positive blood culture tests for Salmonella typhi. The Typhifast IgM and Enterocheck WB showed sensitivity of 97.01% and 68.52%, respectively. Specificity was also more with Typhifast IgM (85.07%) than with Enterocheck WB (62.96%). When tests were used in parallel combination, 97.01% sensitivity was attained, while the specificity dropped to 46.30%. When used in serial combination, sensitivity of 85.07% and specificity of 85.19% were observed. CONCLUSION: Stepladder fever, abnormal serum glutamic oxaloacetic transaminase (SGOT), and abnormal albumin are associated with blood culture, Typhifast IgM, and Enterocheck WB tests. Rapid serological tests might assist in accurate and early identification of TF. HOW TO CITE THIS ARTICLE: Bhume RJ, Babaliche P. Clinical Profile and the Role of Rapid Serological Tests: Typhifast IgM and Enterocheck WB in the Diagnosis of Typhoid Fever. Indian J Crit Care Med 2020;24(5):307-312.

Typhoid fever among febrile Nigerian patients: Prevalence, diagnostic performance of the Widal test and antibiotic multi-drug resistance.

Background: Over-dependence on clinical presentation and/or the Widal agglutination test for the diagnosis of typhoid fever in developing countries can lead to antibiotic abuse. In Nigeria, the antibiotic resistance of typhoid organisms is poorly characterized. In this study, we determined the prevalence of culture positivity among patients suspected of having typhoid fever, evaluated the diagnostic value of the Widal test and the burden created by the multi-drug resistance of typhoid organisms in South-East Nigeria. Methodology: This was a prospective and case-controlled study carried out between 2013 and 2016. We acquired samples of blood/stool/urine cultures, and data relating to the Widal agglutination test and malaria parasites from 810 febrile patients (suspected of having typhoid) and 288 apparently healthy controls. Individuals with a history of antibiotic use within the previous 14 days were excluded. We then carried out antibiotic susceptibility tests on all isolates. Multi-drug resistance was defined as a resistance to ≥3 of the antibiotics tested. We determined the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of Widal test for typhoid laboratory diagnosis compared to bacterial culture which is the gold standard. A P-value <0.05 was considered to be statistically significant. Results: The mean age of typhoid suspects was 33.1±6.5 years and 50.7% were women. Of the 810 typhoid suspects tested, 114 (14.1%) had positive cultures for the typhoid organisms Salmonella enterica serovar paratyphi (72) and S. enterica serovar Typhi (42). Sample-specific rates of culture positivity were as follows: stool (72; 8.9%), blood (21; 2.6%) and urine (21; 2.6%), P<0.001. None of the controls had typhoid isolates. The sensitivity, specificity, PPV and NPV of the Widal test were 49.1%, 90.7%, 46.2% and 91.6%, respectively. Malaria parasitaemia was detected in 180 (22.2%) febrile patients, out of whom 115 (63.9%) had a positive Widal test for O/H antigens vs. 1% (6/630) in those with negative malaria parasite test results (P<0.001). The rate of false-positive Widal titres was 48%. Antibiotic multi-drug resistance was detected in 52.6% of patients. The antibiotics with the highest susceptibility were ciprofloxacin, levofloxacin and meropenem (all 100% susceptibility) and ceftriaxone (95.6% susceptibility). Conclusion: Our data showed that while typhoid fever is common in Nigeria, malaria is more prevalent. Our analysis showed that the Widal test performed poorly as a diagnostic test and that the burden created by multi-drug resistance was high. Our data indicate that periodic surveillance of antibiotic susceptibility is critical for optimal typhoid therapy.

Achieving accurate laboratory diagnosis of typhoid fever: a review and meta-analysis of TUBEX® TF clinical performance.

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.

Performance of Widal test and stool culture in the diagnosis of typhoid fever among suspected patients in Dar es Salaam, Tanzania.

OBJECTIVE: We set an experiment to determine the diagnostic performance of the Widal test and stool culture in typhoid-suspected cases attending tertiary hospitals in Dar es Salaam, Tanzania using blood culture as a golden standard. We also evaluated the agreement between Widal, stool and blood culture. RESULTS: This was a cross-sectional study conducted between June and September 2018, in three Regional Referral Hospitals in Dar es Salaam, Tanzania. A total of 158 typhoid-suspected cases were enrolled, after obtaining an informed consent. Of the 158 patients participated in the study, 128 (81%) tested positive for the Widal test and 17 (11%) patients were stool culture positive. Widal test recorded 81.5% sensitivity, 18.3% specificity, 10.1% positive predictive value and 89.7% negative predictive value. Stool culture showed 31.3% sensitivity, 91.5% specificity, 29% positive predictive value and 91.5% negative predictive value. In conclusion, Widal test is not reliable for diagnosis of typhoid fever since false positive and negative results are common. In addition, Widal test recorded poor agreement with the blood culture (kappa = 0.014, p < 0.05) while stool culture had strong agreement with the blood culture (kappa = 0.22, p < 0.05).

Hemophagocytic lymphohistiocytosis as a diagnostic consideration of fever of unknown origin with pancytopenia and chronic liver disease.

Hemophagocytic lymphohistiocytosis (HLH) is a severe disorder of systemic immune dysregulation which can be primary or secondary to autoimmune disorders, malignancy, or infections. We hereby describe a case of a 23-year-old male with severe hepatitis along with pancytopenia and prolonged fever of unknown origin that developed HLH triggered by staphylococcal urinary tract infection. This is a discussion of this unusual disease and its presentation and the diagnostic difficulties which may be encountered in general clinical practice.

A cross-sectional study of enteric fever among febrile patients at Ambo hospital: prevalence, risk factors, comparison of Widal test and stool culture and antimicrobials susceptibility pattern of isolates.

BACKGROUND: Enteric fever is one of the common infectious diseases of humans. The objectives of this study were to:1) estimate the prevalence of enteric fever among febrile patients visiting Ambo hospital; 2) comparison of Widal test and stool culture;3) evaluation of the antimicrobial susceptibility of isolates; and 4) assess potential risk factors to acquire enteric fever infection. METHODS: Blood and stool samples were collected from 372 febrile patients with symptoms clinically similar to enteric fever. Widal test was used for testing sera while stool culturing and bacterial identification was done using WHO standard methods. Susceptibility testing was done using Kirby-Bauer disc diffusion method. Chi-Square test and Logistic Regression analysis were used to analyze the data. RESULTS: The apparent and true prevalence of enteric fever were 56.2% (95% confidence interval [CI]: 50.97-61.29%) and 57.52% (95% CI: 52.3-62.6%) respectively, while, the culture prevalence was 2.7% (95% CI: 1.30-4.89%). Isolation rates of S. Typhi and S. Paratyphi were 0.8% (95% CI: 0.17-2.34%) and 1.9% (95% CI: 0.76-3.84%) respectively. The isolates showed 100% resistance to amoxicillin, bacitracin, erythromycin, 80%resistance to cefotaxime and streptomycin and 20% for chloramphenicol. The sensitivity, specificity, positive and negative predictive values of Widal test was 80.0, 44.5, 3.8 and 98.8% respectively. Multivariable logistic regression analysis revealed that age (adjusted odds ratio [aOR] = 2.45; 95% CI: 1.38-4.37; P = 0.002), religion (aOR = 15.57, 95% CI: 3.01-80.64; P = 0.001), level of education (aOR = 2.60, 95% CI: 1.27-5.28; P = 0.009), source of water (aOR = 2.20, 95% CI: 1.21-3.98; P = 0.009), raw milk (aOR =2.19, 95% CI:1.16-4.16; P = 0.016) and raw meat consumption (aOR = 1.80, 95% CI: 1.07-3.01; P = 0.026) are the predictors of enteric fever seropositivity. CONCLUSIONS: Patients were wrongly diagnosed and treated for enteric fever by Widal test. Therefore, rapid tests with better sensitivity and specificity are needed for the diagnosis of enteric fever. Provision of safe water and health education are vital to bring behavioral change towards raw food consumption.

Baseline Widal Titer Among Healthy Adult Males from the Greater Mymensingh Division of Bangladesh.

BACKGROUND: Widal test is the most widely used laboratory investigation for diagnosis of typhoid. However, the test interpretation remains controversial in the context of endemic regions such as Bangladesh, as agglutination occurs at varied titrations among a large percentage of healthy population. Paired Widal tests are often not feasible; hence single unpaired test has to be used for screening, diagnosis and treatment. OBJECTIVE: We aimed to assess the normal range of baseline titre for Anti TO, TH, AO, AH, BO agglutinins among healthy population in an endemic country with a view to guide the researchers and the clinicians, facilitating further investigation on updating cut off points of single Widal test for screening and diagnosis of typhoid fever in the context of Bangladesh. METHODS: A cross-sectional study was carried out in Mymensingh Medical College, Bangladesh on 2925 male immigration applicants. A single blood sample was collected for Widal test and interpreted using standard guidelines. RESULTS: The highest baseline titer for Anti TO, TH, AO, AH, BO agglutinins among 95% of the healthy participants was found to be 1:80 for each respectively. A titre of 1: 40 was observed for BH antigen. CONCLUSION: In case of singular Widal test, baseline values for the normal range was found to be 1:20 - 1:80 for all the antigens (TO, TH, AO, AH, BO, BH), except BH, for which it was 1:20-1:40. Further studies, inclusive of other sociodemographic groups and positive controls are required to determine the updated cut off values.

Molecular diagnosis of Salmonella typhi and its virulence in suspected typhoid blood samples through nested multiplex PCR.

A nested multiplex polymerase chain reaction (PCR) based diagnosis was developed for the detection of virulent Salmonella typhi in the blood specimens from patients suspected for typhoid fever. After the Widal test, two pairs of primers were used for the detection of flagellin gene (fliC) of S. typhi. Among them, those positive for fliC alone were subjected to identification of genes in Via B operon of Salmonella Pathogenesity Island (SPI-7) where four primer pairs were used to detect tviA and tviB genes. Among 250 blood samples tested, 115 were positive by fliC PCR; 22 of these were negative for tviA and tviB. Hence, the method described here can be used to diagnose the incidence of Vi-negative serovar typhi especially in endemic regions where the Vi vaccine is administered.

A Comparative Evaluation of Different Diagnostic Modalities in the Diagnosis of Typhoid Fever Using a Composite Reference Standard: A Tertiary Hospital Based Study in Central India.

INTRODUCTION: Enteric fever, caused by Salmonella spp. is a major cause of morbidity and mortality worldwide and endemic in many developing countries including India and other South-East Asian countries. Blood culture is regarded as the gold standard for diagnosis. Currently, the standard serological method is tube agglutination with moderate sensitivity and specificity. Dot blot assay detecting IgM and IgG antibodies to a specific 50kD Outer Membrane Protein (OMP) antigen of Salmonella spp. is a simple, reliable, affordable and rapid test which can help in the early diagnosis of typhoid fever. AIM: To systematically evaluate the different diagnostic modalities against a composite reference standard for the better diagnosis of typhoid fever in clinically suspected cases of typhoid fever. MATERIALS AND METHODS: This cross-sectional, prospective analytical study was carried out at a tertiary care hospital attached to Medical College in central India from November 2011 to June 2013. A total of 163 blood samples, collected aseptically from patients clinically diagnosed of enteric fever, were tested using various component tests like blood culture, Tube Widal and Dot Enzyme Immuno Assay (Dot EIA) for IgG and/or IgM. Composite Reference Standard (CRS) was created for defining the confirmed cases of typhoid fever using the component tests, wherein culture positive and in absence of culture positivity any two component test positive patients were taken as confirmed cases. All the component tests were evaluated against the CRS for sensitivity, specificity, PPV and NPV and their significance in relation to the duration of illness using statistical tests of significance. RESULTS: Blood culture was positive in 16 (9.81%) whereas, Tube Widal, IgM, IgG and IgM+IgG in combination were positive in 88(54%), 58(35.58%), 30 (18.40%) and 75 (46.01%) respectively. Using a two test criteria of CRS framed, a total of 104 patients were considered as confirmed cases. Though specificity of blood culture was 100%, the sensitivity was low with significant detection rate in 1st week of illness. Tube Widal showed a sensitivity of 65.38% and specificity of 89.83% with significant detection rate in 2nd week. Dot blot assay for IgM, IgG and Combined IgM and IgG showed a sensitivity of 71.15%, 65.28% and 51.72% respectively whereas, the specificity was 10.16%, 47.45% and 74.57% respectively with significant detection rate in 2nd and 3rd week of illness. CONCLUSION: It can be concluded that though blood culture is still the gold standard, Dot blot assay found to have high sensitivity and good specificity might be a practical alternative test for the rapid diagnosis of typhoid fever if interpreted with care particularly using a composite reference standard. Further, it is reliable, simple to perform and rapid; results being available in 1 hour when compared to 48 hours for blood culture and 18 hours for Tube Widal test.

Comparative Evaluation of Tubex TF (Inhibition Magnetic Binding Immunoassay) for Typhoid Fever in Endemic Area.

BACKGROUND: Typhoid fever remains a significant health problem in endemic countries like India. Various serological tests for the diagnosis of typhoid fever are available commercially. We assessed the usefulness of rapid test based on magnetic particle separation to detect Immunoglobulin against Salmonella typhi O9 lipopolysaccharide. AIM: Aim of this study was to compare the sensitivity and specificity of widal test, typhidot and tubex TF test for the diagnosis of typhoid fever in an endemic country like India. MATERIALS AND METHODS: Serum samples collected from 50 patients of typhoid fever, 50 patients of non typhoid fever and 100 normal healthy individuals residing in Amritsar were subjected to widal test, typhidot test and tubex TF test as per manufacturer's instructions. Data collected was assessed to find sensitivity and specificity of these tests in an endemic area. RESULTS: Significant widal test results were found positive in 68% of patients of typhoid fever and only 4% of non typhoid fever patients. Typhidot (IgM or IgG) was positive in 72% of typhoid fever patients and 10% and 6% in non typhoid fever and normal healthy individuals respectively. Tubex TF showed higher sensitivity of 76% and specificity of 96-99% which was higher than typhidot and comparable to widal test. CONCLUSION: This was the first evaluation of rapid tubex TF test in northern India. In countries which can afford high cost of test, tubex TF should be recommended for the diagnosis in acute stage of the disease in clinical setting. However, there is urgent need for a highly specific and sensitive test for the diagnosis of typhoid fever in clinical settings in endemic areas.

Diagnosis and Treatment of Typhoid Fever and Associated Prevailing Drug Resistance in Northern Ethiopia.

OBJECTIVE: To determine diagnostic value of the Widal test, treatment pattern of febrile patients and antimicrobial drug susceptibility pattern of blood isolates. METHODS: Using cross sectional methods, blood samples were collected for culture and Widal test from 502 febrile outpatients attending Mekelle hospital and Mekelle health center with similar symptoms to typhoid. Sensitivity, specificity for anti-TH and anti-TO titers using culture confirmed typhoid fever cases, and Kappa agreement between Titer and slide Widal tests were calculated. Treatment pattern of patients and antimicrobial susceptibility pattern of the blood isolates was assessed. RESULTS: From the 502 febrile patients, 8(1.6%) of them had culture-proven typhoid fever. However, patients who have results indicative of recent infection by O and H antigens of the Widal slide agglutination test were 343 (68.5%), with specificity and sensitivity of 33% and 100%, respectively. Over prescription of antibiotics was seen by Widal slide test for Ciprofloxacin 268 (76.1%), Amoxicillin- Clavulanic acid 9(2.6%), Amoxicillin 8(2.4%) and Chloranphenicol 8(2.4%). Tube titer positivity was seen in 23(5.3%) patients with 75% sensitivity and 95.8% specificity. Widal slide and Tube titer tests showed poor agreement for both antigens (kappa=0.02 for O) and (Kappa=0.09 for H). A single anti-TH titer of ≥ 1:160 and anti-TO titer ≥ 1:80 higher in our study showed an indication for typhoid fever infection. Drug resistance pattern of blood isolates ranges from 0-89.7% for gram positive and 0-100% for Gram negative, with an overall multi-drug resistance rate of 61.7%. CONCLUSION: Patients were wrongly diagnosed and treated for typhoid fever by Widal test. The tube titration method was relatively good but still had poor sensitivity. Blood isolates showed multi drug resistance, which may be due to the indiscriminate prescription as seen in this study. Based on our results, the slide Widal test is not helpful in the diagnosis of typhoid, hence other tests with rapid, feasible, better sensitivity and specificity are urgently needed in Ethiopia.

Comparative evaluation of various tests for diagnosis of concurrent malaria and typhoid Fever in a tertiary care hospital of northern India.

BACKGROUND: Malaria and Typhoid are two major infectious diseases, still prevalent in most of the tropical countries including India. Millions of individuals residing in these endemic cases contact these diseases either concurrently or as acute infection superimposed on a chronic one. AIM: Diagnosis and comparative evaluation of various tests for diagnosis of Typhoid- Malaria co-infection in patients suffering from febrile illness. MATERIALS AND METHODS: Around 800 patients of both Out Patient Department (OPD) and In Patient Department (IPD) were referred to microbiology lab for Widal test/ Typhi dot IgG/IgM and Malaria card test between July 2012- September 2012. Patients found to be suffering from co-infection were further confirmed for typhoid by blood culture. Those patients who were found sterile on blood culture were further confirmed by stool culture. Patients positive by Malaria card test (either antibody or antigen or both) were confirmed by peripheral blood smear examination for malaria parasite by both thick and thin smear examination. RESULT: 68 (8.5%) patients were found to be suffering from co- infection by the above tests. Blood culture revealed 15 (22%) bacterial pathogens in the widal positive patients out of which 6(8.8%) were Salmonella Typhi and 3 (4.41%) were Salmonella Paratyphi A. Stool culture revealed 8 (11.7%) S.Typhi and 5 (7.35%) S. Paratyphi A cases. Out of 68 patients positive by Malaria card test, only 36 (52.94%) showed Malaria parasite in peripheral blood smear also. Thus the no. of confirmed cases of co-infection was found to be only 1.6%. CONCLUSION: The interpretation of Widal test and Malaria card test, when diagnosing concurrent malaria and typhoid fever, must therefore be done with a lot of caution. Negative or positive Widal agglutination test is neither definitive nor completely informative. Similarly erroneous interpretation of Malaria card test (especially Antibody detection card test) result may lead to prolonged treatment and economic burden on patient.

Baseline antibody titres against Salmonella typhi in apparently asymptomatic HIV positive individuals in a tertiary care hospital.

BACKGROUND: Enteric fever is common in tropical regions and is caused by Salmonella enterica serotype typhi (S typhi ). For diagnosis of enteric fever, the Widal test is the most widely used test after blood culture. In HIV infected individuals false positive and false negative Widal reactions are common. The result is variable titres and baseline titres that are unusual in this patient population. AIMS: This study was done to determine the baseline antibody titres for S typhi among HIV infected individuals. METHOD: Average baseline antibody titres against O and H antigens of S typhi were measured by standard Widal test in 200 HIV positive asymptomatic individuals, as well as 200 age and sex-matched controls. The results were compiled and statistically analysed. RESULTS: A total of 84 (42%) of the cases had an H antibody titre of >1:20 and 105 (52.5%) had a titre of >1:20 against O antigen. This implies that positive titre of H and O antigen is significantly associated with HIV positive cases with P<0.001. Correlation of CD4 count with antibody titres shows that there is no significant association between CD4 counts and antibody titres against either H (P=0.634) or O antigen (P=0.765). CONCLUSION: This study shows that HIV infected individuals had increased titres of antibodies against S typhi from the baseline. This indicates a need for evaluation of current cut-off values of diagnostic titres for this group. We also suggest that it is best to perform baseline titres against S t yphi for each patient at the time of diagnosis of HIV status, and to use this for future reference.

Typhidot M and Diazo test vis-à-vis blood culture and Widal test in the early diagnosis of typhoid fever in children in a resource poor setting

OBJECTIVE: Typhoid fever is a major public health problem. A test which is simple, reliable and can be carried out in small laboratories is the need of the hour. We prospectively evaluated typhidot M and Diazo tests vis-à-vis blood culture and Widal test in children. METHODS: Patients aged 6 months to 12 years, having fever of more than four days duration with clinical suspicion of typhoid fever were enrolled. Patients in whom other diagnosis was made served as control. The tests under scrutiny were validated against blood culture and then all the four tests were evaluated among patients who presented in the first week of illness. RESULTS: Blood culture was positive in only 27.3 percent of the cases. Among these culture positive cases, typhidot M test had the highest sensitivity, specificity, PPV and NPV of 90 percent (95 percent CI = 74.4-96.5), 100 percent (95 percent CI = 90.1-100), 100 percent (95 percent CI = 87.5-100), and 92.1 percent (95 percent CI = 79.2-97.3) respectively. Diazo test ranked next with sensitivity, specificity, PPV and NPV of 86.7 percent (95 percent CI = 70.3-94.7), 85.7 percent (95 percent CI = 70.6-93.7), 83.9 percent (95 percent CI = 67.4-92.9), 88.2 percent (95 percent CI = 73.4-95.3) respectively. Among clinically suspected typhoid cases, the overall sensitivity, of blood culture, Widal, typhidot M, Diazo was 27.3 percent (95 percent CI = 19.8- 36.3), 64.6 percent (95 percent CI = 55.3-72.9), 89.1 percent (95 percent CI = 81.9-93.7), 80.9 percent (95 percent CI = 72.6-87.2) respectively. In the first week of illness, typhidot M showed the best sensitivity [86.2 percent (95 percent CI = 69.4-94.5)] followed by Diazo [79 percent (95 percent CI = 61.6-90.2)], Widal [41.4 percent (95 percent CI = 25.5-59.3)] and blood culture [31 percent (95 percent CI = 17.3-49.2)]. CONCLUSION: Both Typhidot M and Diazo are good screening tests for the diagnosis of typhoid fever. Typhidot M is superior to Diazo but the latter is more suitable to resource poor settings being economic and easy to perform.

Evaluation of a Rapid Immunochromatographic Assay Kit for the Diagnosis of Salmonella Typhi Infection / 대한임상미생물학회지

BACKGROUND: Widal test, whose sensitivity and specificity are variable from region to region depending on the incidence of typhoid fever, is still in use and shows a relatively low positive predictive value in Korea. We evaluated a rapid immunochromatographic assay (ICA) kit for the rapid diagnosis of Salmonella Typhi infection. METHODS: Twenty five patients with Salmonella Typhi bacteremia were selected for the patient group. For the control group, 21 nontyphoidal salmonellosis patients, 56 non-Salmonella bacteremia patients, and 57 healthy individuals were selected for evaluating the specificity of ICA test. Each serum specimen was tested with the SD Salmonella Typhi IgG/IgM kits (Standard Diagnostics, Inc., Yongin, Korea). RESULTS: The ICA showed a sensitivity of 100% in Salmonella Typhi patients, and specificities of 61.9%, 82.1% and 91.2% in nontyphoidal salmonellosis patients, non-Salmonella bacteremia patients, and healthy individuals, respectively. The ICA test showed a high sensitivity but a low specificity when compared with the Widal test. CONCLUSION: The ICA test by SD Salmonella Typhi IgG/IgM kit is highly sensitive, but its specificity is relatively low. The ICA test is simple, objective, and suitable for screening typhoid fever.