The Identification of Enteric Fever-Specific Antigens for Population-Based Serosurveillance

J Infect Dis. 2024 Mar 14;229(3):833-844. doi: 10.1093/infdis/jiad242.

Abstract

Background: Enteric fever, caused by Salmonella enterica serovars Typhi and Paratyphi A, is a major public health problem in low- and middle-income countries. Moderate sensitivity and scalability of current methods likely underestimate enteric fever burden. Determining the serological responses to organism-specific antigens may improve incidence measures.

Methods: Plasma samples were collected from blood culture-confirmed enteric fever patients, blood culture-negative febrile patients over the course of 3 months, and afebrile community controls. A panel of 17 Salmonella Typhi and Paratyphi A antigens was purified and used to determine antigen-specific antibody responses by indirect ELISAs.

Results: The antigen-specific longitudinal antibody responses were comparable between enteric fever patients, patients with blood culture-negative febrile controls, and afebrile community controls for most antigens. However, we found that IgG responses against STY1479 (YncE), STY1886 (CdtB), STY1498 (HlyE), and the serovar-specific O2 and O9 antigens were greatly elevated over a 3-month follow up period in S. Typhi/S. Paratyphi A patients compared to controls, suggesting seroconversion.

Conclusions: We identified a set of antigens as good candidates to demonstrate enteric fever exposure. These targets can be used in combination to develop more sensitive and scalable approaches to enteric fever surveillance and generate invaluable epidemiological data for informing vaccine policies.

Clinical trial registration: ISRCTN63006567.

Keywords: IgG antibodies; enteric fever; longitudinal responses; serosurveillance.

MeSH terms

  • Humans
  • Lipopolysaccharides
  • Salmonella enterica*
  • Salmonella paratyphi A
  • Salmonella typhi
  • Typhoid Fever* / epidemiology
  • Typhoid Fever* / prevention & control

Substances

  • Lipopolysaccharides