# Detection of asymptomatic Salmonella enterica serotype Typhi and Paratyphi A carriage by serum antibodies targeting YncE

> **NIH NIH R01** · MASSACHUSETTS GENERAL HOSPITAL · 2020 · $621,384

## Abstract

PROJECT SUMMARY
Salmonella enterica serovars Typhi and Paratyphi A (S. Typhi and S. Paratyphi A) are the predominant causes
of enteric (typhoid/paratyphoid) fever globally, affecting over 11 million people and resulting in over 130,000
deaths each year. A small percentage of acutely infected individuals develop a chronic, but clinically
asymptomatic infection in the biliary tract that can persist for decades. Since S. Typhi and Paratyphi A are
human-restricted pathogens, chronic carriers may act as reservoirs of infection within a community, contribute
to transmission through intermittent shedding of bacteria in feces and urine, and act as vehicles for introducing
these organisms into previously uninfected communities. Therefore, correctly identifying and treating
asymptomatic chronic carriers is critical for the long-term control of enteric fever. Currently, there are no
optimal assays for identifying asymptomatic carriers. Here, we propose to address this deficiency and evaluate
a novel biomarker of S. Typhi and Paratyphi A carriage. We have recently identified that antibodies targeting
YncE (a putative ATP-binding protein) could accurately identify chronic carriers in a pilot study. Our proposal
will include 3 complementary, but independent aims that will further characterize the diagnostic potential of this
antigen and its value as an antigenic target for (1) community-based screening of carriage, (2) as a predictor of
risk of developing carriage following acute disease, and (3) its use as a test of cure following elimination of
carriage. In Aim 1, we will use a cross-sectional analysis to assess the prevalence of anti-YncE responses and
carriage within a typhoid/paratyphoid endemic community. We will then apply a Bayesian latent class model to
examine the utility of using serum anti-YncE responses as an effective screening tool to detect asymptomatic
S. Typhi and S. Paratyphi A carriers at the community level. In Aim 2, we will perform a prospective cohort
analysis to characterize the presence, persistence, and kinetics of antibody responses to YncE following acute
infection and correlate responses with persistent shedding of S. Typhi or S. Paratyphi A. In Aim 3, we will
characterize the presence, persistence, and kinetics of serum anti-YncE responses following elective
cholecystectomy to determine if a fall in anti-YncE antibodies can be used as a test of cure. The results of this
analysis could significantly inform typhoid control programs.

## Key facts

- **NIH application ID:** 9973057
- **Project number:** 5R01AI134814-03
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Richelle C Charles
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $621,384
- **Award type:** 5
- **Project period:** 2018-08-15 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9973057

## Citation

> US National Institutes of Health, RePORTER application 9973057, Detection of asymptomatic Salmonella enterica serotype Typhi and Paratyphi A carriage by serum antibodies targeting YncE (5R01AI134814-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9973057. Licensed CC0.

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