title: Serodiagnosis of Acute Typhoid Fever in Nigerian Pediatric Cases by Detection of Serum IgA and IgG Against Hemolysin E and Lipopolysaccharide.
abstract: Inexpensive, easy-to-use, and highly sensitive diagnostic tests are currently unavailable for typhoid fever. To identify candidate serodiagnostic markers, we have probed microarrays displaying the full Salmonella enterica serovar Typhi (S. Typhi) proteome of 4,352 different proteins + lipopolysaccharides (LPSs), with sera from Nigerian pediatric typhoid and other febrile cases, Nigerian healthy controls, and healthy U.S. adults. Nigerian antibody profiles were broad (∼500 seropositive antigens) and mainly low level, with a small number of stronger "hits," whereas the profile in U.S. adults was < 1/5 as broad, consistent with endemic exposure in Nigeria. Nigerian profiles were largely unaffected by clinical diagnosis, although the response against t1477 (hemolysin E) consistently emerged as stronger in typhoid cases. The response to LPS was also a strong discriminator of healthy controls and typhoid, although LPS did not discriminate between typhoid and nontyphoidal Salmonella (NTS) disease. As a first step toward the development of a point-of-care diagnostic, t1477 and LPS were evaluated on immunostrips. Both provided good discrimination between healthy controls and typhoid/NTS disease. Such a test could provide a useful screen for salmonellosis (typhoid and NTS disease) in suspected pediatric cases that present with undefined febrile disease.
authors.affiliation: Division of Infectious Diseases, School of Medicine, University of California Irvine, California. ddavies@uci.edu.
authors.forename: D Huw
authors.initials: DH
authors.lastname: Davies
authors.affiliation: Division of Infectious Diseases, School of Medicine, University of California Irvine, California.
authors.forename: Aarti
authors.initials: A
authors.lastname: Jain
authors.affiliation: Division of Infectious Diseases, School of Medicine, University of California Irvine, California.
authors.forename: Rie
authors.initials: R
authors.lastname: Nakajima
authors.affiliation: Division of Infectious Diseases, School of Medicine, University of California Irvine, California.
authors.forename: Li
authors.initials: L
authors.lastname: Liang
authors.affiliation: Division of Infectious Diseases, School of Medicine, University of California Irvine, California.
authors.forename: Algis
authors.initials: A
authors.lastname: Jasinskis
authors.affiliation: Division of Infectious Diseases, School of Medicine, University of California Irvine, California.
authors.forename: Medalyn
authors.initials: M
authors.lastname: Supnet
authors.affiliation: Division of Infectious Diseases, School of Medicine, University of California Irvine, California.
authors.forename: Philip L
authors.initials: PL
authors.lastname: Felgner
authors.affiliation: Antigen Discovery, Inc., Irvine, California.
authors.forename: Andy
authors.initials: A
authors.lastname: Teng
authors.affiliation: Antigen Discovery, Inc., Irvine, California.
authors.forename: Jozelyn
authors.initials: J
authors.lastname: Pablo
authors.affiliation: Antigen Discovery, Inc., Irvine, California.
authors.forename: Douglas M
authors.initials: DM
authors.lastname: Molina
authors.affiliation: Department of Pediatrics, University of Nebraska Medical Center, Omaha, Nebraska. International Foundation Against Infectious Diseases in Nigeria, Abuja, Nigeria. Aminu Kano Teaching Hospital, Kano, Nigeria. University of Abuja Teaching Hospital, Gwagwalada, Nigeria.
authors.forename: Stephen K
authors.initials: SK
authors.lastname: Obaro
mesh_terms: D000328:Adult; D000907:Antibodies, Bacterial / Q000032:analysis* / Q000096:biosynthesis; D000942:Antigens, Bacterial / Q000276:immunology*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D006460:Hemolysin Proteins / Q000276:immunology*; D006801:Humans; D007118:Immunoassay; D007070:Immunoglobulin A / Q000032:analysis* / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000032:analysis* / Q000096:biosynthesis; D007223:Infant; D008070:Lipopolysaccharides / Q000276:immunology; D008297:Male; D009549:Nigeria; D040901:Proteomics / Q000379:methods; D011934:Reagent Strips; D012485:Salmonella typhi / Q000276:immunology / Q000302:isolation & purification*; D014435:Typhoid Fever / Q000175:diagnosis* / Q000276:immunology / Q000382:microbiology; D014481:United States
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D006460:Hemolysin Proteins; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D008070:Lipopolysaccharides; D011934:Reagent Strips