Journal
AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
Volume 95, Issue 2, Pages 431-439Publisher
AMER SOC TROP MED & HYGIENE
DOI: 10.4269/ajtmh.15-0869
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Funding
- NIAID [DHHS/NIH/NIAID 5R01AI097493]
- Bill & Melinda Gates Foundation [OPP1034619, OPP1092383]
- Bill and Melinda Gates Foundation [OPP1092383, OPP1034619] Funding Source: Bill and Melinda Gates Foundation
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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 (similar to 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.
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