Diagnostic host gene signature for distinguishing enteric fever from other febrile diseases

Blohmke, Christoph J.; Müller, Julius; Gibani, Malick M.; Dobinson, Hazel; Shrestha, Sonu; Perinparajah, Soumya; Jin, Chunlin; Hughes, Henry J.; Blackwell, Luke; Dongol, Sabina; Karkey, Abhilasha; Schreiber, Fernanda; Pickard, Derek; Basnyat, Buddha; Dougan, Gordon; Baker, Stephen; Pollard, Andrew J.; Darton, Thomas C.

doi:10.15252/emmm.201910431

Cited by 18 publications

(10 citation statements)

References 64 publications

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“…Kanniappan et al first used small RNAs (sRNAs) to detect Mycobacterium tuberculosis , demonstrating sensitivity and specificity of over 95% [ 70 ]. In addition, other infectious diseases such as enteric fever and Kawasaki Disease can also be distinguished via specific gene expression signatures [ 71 , 72 ]. The use of these genetic biomarkers will change the current clinical diagnostic criteria for many infectious diseases.…”

Section: Gene Expression Signaturesmentioning

confidence: 99%

Differential Markers of Bacterial and Viral Infections in Children for Point-of-Care Testing

Tsao

Tsai

Liao

et al. 2020

Trends in Molecular Medicine

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Children suffering from infectious diseases, both bacterial and viral, are often treated with empirical antibiotics. Keeping in mind both the menace of microorganisms and antibiotic toxicity, it is imperative to develop point-of-care testing (POCT) to discriminate bacterial from viral infections, and to define indications for antibiotic treatment. This article reviews potential protein biomarkers and host-derived gene expression signatures for differentiating between bacterial and viral infections in children, and focuses on emerging multiplex POCT devices for the simultaneous detection of sets of protein biomarkers or streamlined gene expression signatures that may provide rapid and cost-effective pathogen-discriminating tools.

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Section: Gene Expression Signaturesmentioning

confidence: 99%

Differential Markers of Bacterial and Viral Infections in Children for Point-of-Care Testing

Tsao

Tsai

Liao

et al. 2020

Trends in Molecular Medicine

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“…A more recent study investigated five host genes as a signature (STAT1, SLAMF8, PSME2, WARS, and ALDH1A1) that was able to identify enteric fever with 88% specificity and 97% sensitivity [ 156 ]. If these signatures are also observed in different endemic areas, amplification of such genes by qPCR-based diagnostic assay can be developed as a promising diagnostic method.…”

Section: Future Directions For New Diagnostic Developmentmentioning

confidence: 99%

Enteric Fever Diagnosis: Current Challenges and Future Directions

2021

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Enteric fever is a life-threatening systemic febrile disease caused by Salmonella enterica serovars Typhi and Paratyphi (S. Typhi and S. Paratyphi). Unfortunately, the burden of the disease remains high primarily due to the global spread of various drug-resistant Salmonella strains despite continuous advancement in the field. An accurate diagnosis is critical for effective control of the disease. However, enteric fever diagnosis based on clinical presentations is challenging due to overlapping symptoms with other febrile illnesses that are also prevalent in endemic areas. Current laboratory tests display suboptimal sensitivity and specificity, and no diagnostic methods are available for identifying asymptomatic carriers. Several research programs have employed systemic approaches to identify more specific biomarkers for early detection and asymptomatic carrier detection. This review discusses the pros and cons of currently available diagnostic tests for enteric fever, the advancement of research toward improved diagnostic tests, and the challenges of discovering new ideal biomarkers and tests.

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“…Therefore, transcriptomic has been used to generate detailed insights into the human transcriptional response to several diseases [55][56][57][58][59][60] and other alternative immune perturbations [54,[60][61][62]. The human challenge model has been the source of various gene expression datasets, which were generated in a highly controlled setting, allowing the interrogation of the human transcriptional responses to S. Typhi and S. Paratyphi A [59,63,64]. This technique use the response of the host as a possible biomarkers that are specific to identify typhoid fever patients.…”

Section: Transcriptomicsmentioning

confidence: 99%

Diversity in Typhoid Diagnostic Protocols And Recommendation for Composite Reference Standard

Igiri¹,

Okoduwa²,

Munirat³

et al. 2021

Preprint

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Typhoid fever is a major public health burden which causes substantial global morbidity and mortality due to lack of decisive diagnostic protocols. The capacity of commonly use diagnostic test to validate the absence of typhoid fever is controversial. This study explores to evaluate new techniques for typhoid diagnosis and proposed a harmonised suitable standardized composite reference to be adopted. Published peer-reviewed articles indexed in PubMed, MEDLINE and Google scholar were reviewed for hospital-based studies. This study reveals new typhoid diagnostic techniques such as proteomics, serology, Rapid Diagnostic tests (RDTs), transcriptomics, genomics, and metabolomics. 34.4% of the studies use prospective study design. The study result establishes that, Widal test has a moderate diagnostic accuracy with average percentage sensitivity (52.9%), specificity (54%), positive predictive value (PPV) (56.8%) as well as negative predictive value (NPV) (55.6%) when compared with 29.4%, 28%, 29.5%, and 27.8% of Typhidot respectively. The findings showed a statistically significant difference on the sensitivity between Widal and Typhidot t (40) = 2.639, p = 0.012 at p<0.05 using independent sample t-test. When there is no perfect reference standard that has an optimal diagnostic accuracy, the need for a harmonised suitable standardized composite reference is essential. Hence, this study recommends that, peripheral blood culture with established sensitivity of 60% and Widal test with average sensitivity of 52.9% be adopted as a consensus composite reference standard for typhoid fever diagnosis in other to improve confidence in prevalence estimates.

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Diagnostic host gene signature for distinguishing enteric fever from other febrile diseases

Cited by 18 publications

References 64 publications

Differential Markers of Bacterial and Viral Infections in Children for Point-of-Care Testing

Differential Markers of Bacterial and Viral Infections in Children for Point-of-Care Testing

Enteric Fever Diagnosis: Current Challenges and Future Directions

Diversity in Typhoid Diagnostic Protocols And Recommendation for Composite Reference Standard

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