Serological Epidemiology and Environment Surveillance Nepal

The absence of credible estimates of the burden of enteric fever has discounted the impact of the disease and thus, prevention and control efforts. There have been efforts to estimate the population-based incidence of enteric fever, but the data on enteric fever associated severity and hospitalization rate, long term complications, and mortality are minimal. Therefore, there is a need to conduct a prospective study in Asian countries with high incidence rates of typhoid fever to better characterize the natural history of the disease and to delineate the impact of severe enteric fever in terms of hospitalization rates and length of stay, complications, and case-fatality rate. The low sensitivity of blood culture and the need for lab infrastructure and time and cost to process cultures continue to limit the ability to diagnose typhoid accurately and efficiently. Other accurate and low-cost diagnostic tests for typhoid are needed for both patient care and to better estimate incidence rates of typhoid fever in the future. In this project, we evaluate a low-cost minimally invasive serologic method for enteric fever surveillance. Such a tool could better-inform estimates of typhoid incidence both current healthcare needs and future areas to target for vaccination. Our study therefore aims to fill multiple evidence gaps: population-based incidence estimates for typhoid and typhoid antimicrobial resistance, including outside of Kathmandu; phylogeographic of S. Typhi; evaluating improved diagnostics for typhoid; and determining whether sero-epidemiology is a viable strategy for estimating the burden of typhoid by comparing serologic data with population-based incidence in the same area.

Study Duration: 01/01/2019-30/06/2021

Objectives:
The sero-epidemiology and environmental surveillance studies are add-on studies to leverage the existing surveillance infrastructure of Phase II of the Surveillance of Enteric Fever in Asia Project (SEAP). The primary goal of the sero-epidemiology component is validating a low-cost serologic tool to distinguish acute typhoid infections from past infections and other illnesses. The primary objective of the environmental surveillance component is to determine the utility of environmental surveillance — quantitative detection of S. Typhi/Para typhi DNA in water samples — as a proxy for the typhoid/paratyphoid disease burden in the community.

Outcomes:
The baseline exposure, in the population, against S. Typhi/Para typhi have been investigated by testing the blood samples for the presence of IgG and IgA antibody. Additionally, the cases that previously had enteric fever have also tested for antibodies against the ag for S. Typhi/Para typhi. We have also detected S. Typhi/Para typhi in river water samples in Kathmandu valley using qPCR method. The bacteriophages specific for S. Typhi/Para typhi have also been isolated and sequenced.

Team Members:

Co-Principal Investigator(s): Dr. Dipesh Tamrakar, Dr Jason Andrews

Co-Investigator(s): Dr. Rajeev Shrestha, Dr. Sailesh Pradhan

Project Coordinator(s): Krista Vaidya, Nishan Katuwal

Research Assistant(s): Sony Shrestha, Sudan Maharjan, Anil Khanal, Bipin Khadka,Lok Raj Bhatt, Suman Shrestha, Natasha Shrestha, Shishir Ranjit
Supported by: Sabin Vaccine Institute, USA
Collaborating Partners: Stanford University, San Francisco, USA