Detection of Salivary IgA Antibodies Against the HlyE Antigen as a Diagnosis of Typhoid Fever

Chin, Kai Ling; Redhuan, Nur Eliyana Mohd; Balaram, Prabha; Phua, Kia Kien; Ong, Eugene Boon Beng

doi:10.7860/jcdr/2016/17801.7909

Cited by 6 publications

(5 citation statements)

References 19 publications

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“…In the previous study, the antigenic protein with the molecular weight of 34 kDa has been identifed, purifed, and characterized as cytolysin, a cytotoxic protein from the outer membrane of S. typhi. Te utility of 34 kDa cytotoxin protein against the IgA antibody has been well demonstrated as a diagnostic biomarker for typhoid fever [31,32]. On the other hand, the WB profle of PHPS recognized the IgA antibody isotype antigenic band at the region of 32 kDa which was not seen in other antibody isotypes.…”

Section: Discussionmentioning

confidence: 99%

Profiling of Humoral Immune Response in Typhoid Patients against Differentially Extracted Whole Cell Bacterial Protein Derived from S. typhi and S. spp

Khan

Kader

2023

Interdisciplinary Perspectives on Infectious Diseases

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Typhoid fever is a multiorgan infectious disease caused by Salmonella typhi. It is transmitted through fecal oral route and can be fatal without proper treatment. Therefore, early diagnosis of typhoid fever is crucial. In the previous study, we have developed TYPHOIDYNE EIA, which showed excellent synergy between the genus conserved and species-specific antigens in the serodiagnosis of typhoid fever. TYPHOIDYNE EIA can effectively detect and differentiate typhoid patients, typhoid vaccinated subjects, healthy subjects, and subjects with other febrile illnesses. Following the successful development of TYPHOIDYNE EIA, in this report, we further characterize the antigenic components of differentially extracted S. typhi and S. spp recognized by IgM, IgG, and IgA antibody isotypes in typhoid patients and possible typhoid carrier by the western blot (WB) assay. The WB characterization revealed a dynamic pattern of recognition, with significant variations in the number of antigenic bands observed between the differentially extracted arrays of antigens. The reactivity of patient’s sera was divided into 3 regions, with region 1 (≥55 kDa) showing the strongest reactivity followed by region 2 (54 kDa–34 kDa) and region 3 (<34 kDa). Overall, the good synergy expressed in these bands suggests the potential role of these proteins in differentiating typhoid patients with possible typhoid carrier. The antigenic bands highlighted in this study are also identified as prospective biomarkers for diagnostic use and vaccine development.

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Section: Discussionmentioning

confidence: 99%

Profiling of Humoral Immune Response in Typhoid Patients against Differentially Extracted Whole Cell Bacterial Protein Derived from S. typhi and S. spp

Khan

Kader

2023

Interdisciplinary Perspectives on Infectious Diseases

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“…This precluded re-testing or bacterial culturing, which is currently considered as the diagnostic gold standard despite varying sensitivity ranging between 45 and 70% [ 45 ]. In addition, antibiotic pre-treatment as reported by FSs in Diego, Mahajanga and Adama Zuria is known to impact diagnostic sensitivity though data collected may be incorrect due to recall bias [ 48 ]. The bacterial load present in each specimen could have a significant impact on the diagnostic sensitivity of both, antibody detection by ELISA and DNA amplification by RT-PCR [ 6 ].…”

Section: Discussionmentioning

confidence: 99%

Detection of Salmonella Typhi nucleic acid by RT-PCR and anti-HlyE, -CdtB, -PilL, and -Vi IgM by ELISA at sites in Ghana, Madagascar and Ethiopia

et al. 2022

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Background We aimed to assess the prevalence of Salmonella Typhi through DNA and IgM-antibody detection methods as a prelude to extended surveillance activities at sites in Ghana, Madagascar, and Ethiopia. Methods We performed species-specific real-time polymerase reaction (RT-PCR) to identify bacterial nucleic acid, and enzyme-linked immunosorbent assay (ELISA) for detecting HlyE/STY1498-, CdtB/STY1886-, pilL/STY4539- and Vi-antigens in blood and biopsy specimens of febrile and non-febrile subjects. We generated antigen-specific ELISA proxy cut-offs by change-point analyses, and utilized cumulative sum as detection method coupled with 1000 repetitive bootstrap analyses. We computed prevalence rates in addition to odds ratios to assess correlations between ELISA outcomes and participant characteristics. Results Definitive positive RT-PCR results were obtained from samples of febrile subjects originating from Adama Zuria/Ethiopia (1.9%, 2/104), Wolayita Sodo/Ethiopia (1.0%, 1/100), Diego/Madagascar (1.0%, 1/100), and Kintampo/Ghana (1.0%, 1/100), and from samples of non-febrile subjects from Wolayita Sodo/Ethiopia (1%, 2/201). While IgM antibodies against all antigens were identified across all sites, prevalence rates were highest at all Ethiopian sites, albeit in non-febrile populations. Significant correlations in febrile subjects aged < 15 years versus ≥ 15 years were detected for Vi (Odds Ratio (OR): 8.00, p = 0.034) in Adama Zuria/Ethiopia, STY1498 (OR: 3.21, p = 0.008), STY1886 (OR: 2.31, p = 0.054) and STY4539 (OR: 2.82, p = 0.022) in Diego/Madagascar, and STY1498 (OR: 2.45, p = 0.034) in Kintampo/Ghana. We found statistical significance in non-febrile male versus female subjects for STY1498 (OR: 1.96, p = 0.020) in Adama Zuria/Ethiopia, Vi (OR: 2.84, p = 0.048) in Diego/Madagascar, and STY4539 (OR: 0.46, p = 0.009) in Kintampo/Ghana. Conclusions Findings indicate non-discriminatory stages of acute infections, though with site-specific differences. Immune responses among non-febrile, presumably healthy participants may mask recall and/or reporting bias leading to misclassification, or asymptomatic, subclinical infection signs induced by suppression of inflammatory responses. As most Ethiopian participants were ≥ 15 years of age and not at high-risk, the true S. Typhi burden was likely missed. Change-point analyses for generating ELISA proxy cut-offs appeared robust, though misclassification is possible. Our findings provided important information that may be useful to assess sites prior to implementing surveillance for febrile illness including Salmonella disease.

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“…Another antigen that is frequently studied is HlyE, with all isotypes of antibodies having been evaluated. Since the first report of the presence of HlyE-reactive antibodies in typhoid patients in 2006 [ 36 ], several studies have shown that antibodies against the S. Typhi HlyE antigen are a promising biomarker for the detection of individuals with acute typhoid infections due to their ability to discriminate between typhoid cases and healthy individuals [ 37 , 38 ]. HlyE is a pore-forming cytotoxin of a 34 kDa protein that assembles into a ring-shaped dodeca-oligomer that forms stable pores in host membranes [ 39 ].…”

Section: Discussionmentioning

confidence: 99%

Performance of Immunodiagnostic Tests for Typhoid Fever: A Systematic Review and Meta-Analysis

et al. 2021

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Typhoid fever, also known as typhoid, is a life-threatening bacterial infection that remains a global health concern. The infection is associated with a significant morbidity and mortality rate, resulting in an urgent need for specific and rapid detection tests to aid prevention and management of the disease. The present review aims to assess the specificity and sensitivity of the available literature on the immunodiagnostics of typhoid fever. A literature search was conducted using three databases (PubMed, ProQuest and Scopus) and manual searches through the references of identified full texts to retrieve relevant literature published between 1 January 2011 and 31 December 2020. Of the 577 studies identified in our search, 12 were included in further analysis. Lipopolysaccharides (LPS) and hemolysin E (HlyE) were the most frequently studied antigens. The specimens examined in these studies included serum and saliva. Using blood culture as the gold standard, anti-LPS IgA gave the highest sensitivity of 96% (95% CI: 93–99) and specificity of 96% (95% CI: 93–99) for distinguishing between typhoid cases and healthy controls, whereas the combination of anti-LPS and anti-flagellin total IgGAM gave the highest sensitivity of 93% (95% CI: 86–99) and specificity of 95% (95% CI: 89–100) for distinguishing typhoid cases and other febrile infections. A comparably high sensitivity of 92% (95% CI: 86–98) and specificity of 89% (95% CI: 78–100) were shown in testing based on detection of the combination of anti-LPS (IgA and IgM) and anti-HlyE IgG as well as a slightly lower sensitivity of 91% (95% CI: 74–100) in the case of anti-50kDa IgA. Anti-50kDa IgM had the lowest sensitivity of 36% (95% CI: 6–65) against both healthy and febrile controls. The development of a rapid diagnostic test targeting antibodies against lipopolysaccharides combined with flagellin appeared to be a suitable approach for the rapid detection test of typhoid fever. Saliva is added benefit for rapid typhoid diagnosis since it is less invasive. As a result, further studies could be done to develop additional approaches for adopting such samples.

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Detection of Salivary IgA Antibodies Against the HlyE Antigen as a Diagnosis of Typhoid Fever

Cited by 6 publications

References 19 publications

Profiling of Humoral Immune Response in Typhoid Patients against Differentially Extracted Whole Cell Bacterial Protein Derived from S. typhi and S. spp

Profiling of Humoral Immune Response in Typhoid Patients against Differentially Extracted Whole Cell Bacterial Protein Derived from S. typhi and S. spp

Detection of Salmonella Typhi nucleic acid by RT-PCR and anti-HlyE, -CdtB, -PilL, and -Vi IgM by ELISA at sites in Ghana, Madagascar and Ethiopia

Performance of Immunodiagnostic Tests for Typhoid Fever: A Systematic Review and Meta-Analysis

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