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Analysis of Serum YncE Responses in Patients with S. TYPHI/PARA TYPHI Carriage Following Elective Cholecystectomy

We are at a critical and rapidly evolving juncture for global typhoid control. There is a spreading extensively drug resistant S. Typhi outbreak in Pakistan, and there have been increasing efforts toward typhoid control. A Vi-conjugate vaccine from India was recently WHO-prequalified; WHO recently published a position statement endorsing its use; and Gavi, the Vaccine Alliance, has pledged $85 million to scale up its roll out. However, unless chronic carriers are identified and treated as part of these control programs, any decrease in typhoidal burden based on vaccine use alone may be transient, since carriers are already present in these populations and may re-seed typhoidal outbreaks. NB: While Vi vaccines protect against acute typhoid fever and thus, hopefully will limit the number of future carriers; vaccination does not affect the burden of already established carriers. Prior studies in Kathmandu Nepal have shown that the rate of S. Typhi and S. Para typhi A isolation in bile from patients undergoing elective cholecystectomy (i.e., carriage) is 3.3%.

Study Duration: 04/01/2019 – 03/31/2023

Objectives:

The goal of this study is to address the gap in diagnostics for typhoid/paratyphoid carriers. We plan to establish whether the antigen that we have identified (YncE) has utility as an antigenic target for such diagnostic setup and whether it can be used as a test of cure. In addition, one of the goals of our analysis is to compare anti-YncE to anti-Vi responses for detection of carriage.

Outcomes:

In this study, we have detected carriers of S. Typhi/Para typhi through culture and molecular detection (qPCR) in bile, gallbladder tissues and gallstones. Additionally, we have identified AMR pattern of the isolated S. Typhi/Para typhi. Furthermore, the anti-YncE level of those carriers are being studied over a follow-up time, to observe clearance of carriage.

Team Members

Co-Principal Investigator(s): Prof. Dr. Rajeev Shrestha, Dr. Richelle Charles, Dr. Bala Ram Malla

Project Director: Prof. Dr. Rajeev Shrestha

Co-Investigator(s): Dr. Srijana Ranjit, Dr. Mukunda Joshi, Dr. Sailesh Pradhan, Dr. Roshan Ghimire

Project Coordinator: Nishan Katuwal

Research Assistants: Laxmi Chauguthi, Manisha Banjara, Nisha Shrestha, Natasha Shrestha, and Shishir Ranjit

Supported by: National Institute of Health (NIH)

Collaborating Partners: Harvard Medical School and Massachusetts General Hospital, Boston, USA