title: Development of a Simple, Peripheral-Blood-Based Lateral-Flow Dipstick Assay for Accurate Detection of Patients with Enteric Fever.
abstract: Enteric fever is a systemic infection caused by typhoidal strains of Salmonella enterica and is a significant cause of mortality and morbidity in many parts of the world, especially in resource-limited areas. Unfortunately, currently available diagnostic tests for enteric fever lack sensitivity and/or specificity. No true clinically practical gold standard for diagnosing patients with enteric fever exists. Unfortunately, microbiologic culturing of blood is only 30 to 70% sensitive although 100% specific. Here, we report the development of a lateral-flow immunochromatographic dipstick assay based on the detection of Salmonella enterica serovar Typhi (S Typhi) lipopolysaccharide (LPS)-specific IgG in lymphocyte culture secretion. We tested the assay using samples from 142 clinically suspected enteric fever patients, 28 healthy individuals residing in a zone where enteric fever is endemic, and 35 patients with other febrile illnesses. In our analysis, the dipstick detected all blood culture-confirmed S Typhi cases (48/48) and 5 of 6 Salmonella enterica serovar Paratyphi A blood cultured-confirmed cases. The test was negative in all 35 individuals febrile with other illnesses and all 28 healthy controls from the zone of endemicity. The test was positive in 19 of 88 individuals with suspected enteric fever but with negative blood cultures. Thus, the dipstick had a sensitivity of 98% compared to blood culture results and a specificity that ranged from 78 to 100% (95% confidence interval [CI], 70 to 100%), depending on the definition of a true negative. These results suggest that this dipstick assay can be very useful for the detection of enteric fever patients especially in regions of endemicity.
authors.affiliation: Incepta Pharmaceuticals Ltd., Savar, Dhaka, Bangladesh.
authors.forename: Iqbal Hassan
authors.initials: IH
authors.lastname: Khan
authors.affiliation: International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka, Bangladesh.
authors.forename: M Abu
authors.initials: MA
authors.lastname: Sayeed
authors.affiliation: Incepta Pharmaceuticals Ltd., Savar, Dhaka, Bangladesh.
authors.forename: Nishat
authors.initials: N
authors.lastname: Sultana
authors.affiliation: International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka, Bangladesh.
authors.forename: Kamrul
authors.initials: K
authors.lastname: Islam
authors.affiliation: Incepta Pharmaceuticals Ltd., Savar, Dhaka, Bangladesh.
authors.forename: Jakia
authors.initials: J
authors.lastname: Amin
authors.affiliation: International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka, Bangladesh.
authors.forename: M Omar
authors.initials: MO
authors.lastname: Faruk
authors.affiliation: Incepta Pharmaceuticals Ltd., Savar, Dhaka, Bangladesh.
authors.forename: Umama
authors.initials: U
authors.lastname: Khan
authors.affiliation: International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka, Bangladesh.
authors.forename: Farhana
authors.initials: F
authors.lastname: Khanam
authors.affiliation: Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, USA.|Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA.|Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts, USA.
authors.forename: Edward T
authors.initials: ET
authors.lastname: Ryan
authors.affiliation: International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka, Bangladesh fqadri@icddrb.org.
authors.forename: Firdausi
authors.initials: F
authors.lastname: Qadri
mesh_terms: D000293:Adolescent; D000328:Adult; D000907:Antibodies, Bacterial / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D002846:Chromatography, Affinity / Q000295:instrumentation / Q000379:methods* / Q000592:standards; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood*; D007223:Infant; D008070:Lipopolysaccharides / Q000276:immunology; D008297:Male; D008875:Middle Aged; D012482:Salmonella paratyphi A / Q000276:immunology*; D012485:Salmonella typhi / Q000276:immunology*; D012680:Sensitivity and Specificity; D014435:Typhoid Fever / Q000175:diagnosis* / Q000276:immunology / Q000382:microbiology; D055815:Young Adult
chemical_list: D000907:Antibodies, Bacterial; D007074:Immunoglobulin G; D008070:Lipopolysaccharides