Abstract
SummaryObjectivesThe diagnosis of typhoid fever is a challenge. Aiming to develop a typhoid diagnostic we measured antibody responses against Salmonella Typhi (S. Typhi) protein antigens and the Vi polysaccharide in a cohort of Bangladeshi febrile patients.MethodsIgM against 12 purified antigens and the Vi polysaccharide was measured by ELISA in plasma from patients with confirmed typhoid fever (n = 32), other confirmed infections (n = 17), and healthy controls (n = 40). ELISAs with the most specific antigens were performed on plasma from 243 patients with undiagnosed febrile disease.ResultsIgM against the S. Typhi protein antigens correlated with each other (rho > 0.8), but not against Vi (rho < 0.6). Typhoid patients exhibited higher IgM against 11/12 protein antigens and Vi than healthy controls and those with other infections. Vi, PilL, and CdtB exhibited the greatest sensitivity and specificity. Specificity and sensitivity was improved when Vi was combined with a protein antigen, generating sensitivities and specificities of 0.80 and >0.85, respectively. Applying a dynamic cut-off to patients with undiagnosed febrile disease suggested that 34–58% had an IgM response indicative of typhoid.ConclusionsWe evaluated the diagnostic potential of several S. Typhi antigens; our assays give good sensitivity and specificity, but require further assessment in differing patient populations.
Highlights
Enteric fever is a systemic infection caused by Salmonella enterica serovars Typhi
IgM against 12 purified antigens and the Vi polysaccharide was measured by ELISA in plasma from patients with confirmed typhoid fever (n Z 32), other confirmed infections (n Z 17), and healthy controls (n Z 40)
ELISAs with the most specific antigens were performed on plasma from 243 patients with undiagnosed febrile disease
Summary
Enteric (typhoid) fever is a systemic infection caused by Salmonella enterica serovars Typhi Paratyphi A).[1,2] There are an estimated 12 million cases of typhoid Typhi only) worldwide annually leading to approximately 120,000 deaths.[3,4] The organisms are transmitted via the fecal-oral route and the disease remains common in low/middle income countries in South/ Southeast Asia and sub-Saharan Africa.[5] Despite S. Paratyphi A being an emergent cause of enteric fever in parts of South and Southeast Asia,[6] S. Typhi remains the most commonly reported etiological agent of enteric fever in Asia and Africa
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