Diagnosis and Staging of Typhoid Fever Using Surface-enhanced Raman Spectroscopy Liquid Biopsy

The goal of this project is to adapt the gold nanoparticle-based surface-enhanced Raman spectroscopy (SERS) technology to clinical application. In this exploratory study a measurement protocol will be established to subsequently investigate whether SERS allows to diagnose patients infected with typhoid fever as well as to stage the disease.

Study Overview

• Status: Completed
• Conditions: Typhoid Fever
• Intervention / Treatment: Diagnostic test: Surface-enhanced Raman Spectroscopy

Detailed Description

This study on the clinical application of surface-enhanced Raman spectroscopy (SERS) is composed of two parts. First, a SERS measurement protocol will be developed to enhance the interactions between gold nanoparticles and the components of the patients samples, maximizing Raman spectroscopical signatures. Given the complex composition of human blood, which encompasses numerous biological constituents, the study focuses on serum, a component obtained through centrifugation after the removal of cells and clotting factors. Fifteen spectra will be recorded per sample. The raw spectra will be post-processed, including removal of the substrate signal, baseline correction, vector normalization, and smoothing steps.

The SERS measurement protocol established in the first section will subsequently be applied to samples of healthy and typhoid fever patients. The samples from infected patients will be confirmed with the Widal test. Multivariate data analysis will be performed to identify distinctive feature characteristics in the samples that correlate to their group (healthy and infected patients), allowing patient diagnosis, as well as the severity of the infection.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Northwest
    • Aachen, Northwest, Germany, 52074
      • Roger Molto Pallares

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Patient at Nishtar Medical University
• The age range of the patients was from 18 to 70 years
• Confirmed disease with the Widal test (for typhoid fever groups)

Exclusion Criteria:

• Patients with severe concurrent diseases were excluded from the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Healthy; The serum samples of healthy patients will be measured.	Diagnostic test: Surface-enhanced Raman Spectroscopy; The Raman spectra of patient samples will be measured in the presence of gold nanoparticles, which will enhance the spectroscopic characteristics of serum components via near-field enhancements.
Experimental: Early-stage typhoid fever; The serum samples of early-stage typhoid fever patients will be measured.	Diagnostic test: Surface-enhanced Raman Spectroscopy; The Raman spectra of patient samples will be measured in the presence of gold nanoparticles, which will enhance the spectroscopic characteristics of serum components via near-field enhancements.
Experimental: Consolidated-stage typhoid fever; The serum samples of consolidated-stage typhoid fever patients will be measured.	Diagnostic test: Surface-enhanced Raman Spectroscopy; The Raman spectra of patient samples will be measured in the presence of gold nanoparticles, which will enhance the spectroscopic characteristics of serum components via near-field enhancements.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
SERS measurements to differentiate between healthy and typhoid fever patients	SERS assessment of healthy and typhoid fever patient samples to identify unique spectroscopical characteristics to discriminate between healthy and typhoid fever patients	Through study competition, up to 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
SERS measurements to stage typhoid fever patients	SERS assessment of early-stage and consolidated-stage typhoid fever patient samples to identify unique spectroscopical characteristics to stage the infection.	Through study competition, up to 1 year

Collaborators and Investigators

• Sponsor: University Hospital, Aachen
• Collaborators: Nishtar Medical University; University of Agriculture Faisalabad

Publications and helpful links

General Publications

• Ditta A, Zhang R, Nawaz H, Majeed MI, He S, Zhuang Z, Rutten S, Shahzadi A, Yaseen S, Kiessling F, Hu J, Lammers T, Pallares RM. An exploratory clinical study of the diagnosis and staging of typhoid fever using label-free surface-enhanced Raman spectroscopy liquid biopsy. Spectrochim Acta A Mol Biomol Spectrosc. 2025 Feb 4;333:125864. doi: 10.1016/j.saa.2025.125864. Online ahead of print.

Study record dates

Study Major Dates

• Study Start (Actual): July 15, 2023
• Primary Completion (Actual): August 15, 2024
• Study Completion (Actual): December 15, 2024

Study Registration Dates

• First Submitted: August 2, 2024
• First Submitted That Met QC Criteria: August 6, 2024
• First Posted (Actual): August 9, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 1, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Negative Bacterial Infections; Body Temperature Changes; Enterobacteriaceae Infections; Salmonella Infections; Fever; Typhoid Fever
• Other Study ID Numbers: Typhoid Fever SERS 01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: The study results will be published in at least one scientific article.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No