Protocol No: ECCT/20/10/03 Date of Protocol: 11-08-2020

Study Title:

Comparative study of commercially available typhoid point of care tests to benchmark current and emerging tools

Study Objectives:

General Objective

To compare commercially available typhoid point of care tests to benchmark the golden standard method of blood culture a currently emerging method of PCR.

Primary Objective

  1. To evaluate different RDTs that are commercially available internationally for detecting antigens or antibodies to Salmonella Typhi and use Blood culture as standard for comparison.

Secondary Objectives

  1. Establish a biorepository of well characterized specimen collection that can be used to evaluate emerging tests.
  2. Evaluation of operational characteristics (invalid and indeterminate rates) of Typhoid RDTs
Laymans Summary:

Typhoid fever bacterial disease caused by Salmonella Typhi. It is one of the most common serious bacterial diseases in the developing world, with an estimated 10.9 million people contracting the disease worldwide and 116.8 thousand people dying of the disease in 2017. Culture method using blood and bone marrow samples are considered as the benchmark for teting for typhoid disease. Those methods are however time consuming, requires drawing blood from the body, and requires adequate infrastructure and trained staff that are not available in most of areas where the disease is very common locally. There are other methods but their performance is poor. The Widal test is a cheap test that is widely used despite its high rate of giving test results which wrongly indicates that typhoid is present. Rapid Diagnostic tests (RDTs) have been developed and are available in the market but their performance data are not available or not consistent from one study to another. Therefore, this study will aim to perform a direct comparison of typhoid tests currently in the market to help inform the Ministry of Health in Kenya and the WHO Essential Diagnostic list (EDL) and stakeholder decision making more broadly.

Abstract of Study:

Typhoid fever is an enteric bacterial infection caused by Salmonella enterica serovar Typhi (Salmonella Typhi; S. Typhi). It is an important infectious disease in low- and middle-income countries with over 10.9 million new cases worldwide and 116.8 thousand death in 2017. South Asia and Sub Saharan Africa are the most affected areas of the world. Typhoid fever is common in areas with inadequate sanitation and hyegine. In routine practice, diagnosis of typhoid fever is rarely confirmed as diagnostic tests are unavailable or have limited diagnostic accuracy. Blood culture is the commonest reference standard test but has a lower sensitivity. Bone marrow culture is more sensitive than blood culture yet is rarely used because it requires invasive sampling, adequate infrastructure and skilled staff and mainly used for research purposes. Alternatives to those methods exist but their performance is poor. The Widal test is still used but as it is based on cross-reactive antigens, it lacks sensitivity and specificity. Clinician often use rapid diagnostic tests to diagnose typhoid. A number of typhoid fever RDTs are commercially available but performance data are not available or not consistent from a study to another. Therefore, this study will aim to perform a head to head comparison of typhoid tests currently in the market to help inform Ministry of Health in Kenya and the WHO Essential Diagnostic list (EDL) and stakeholder decision making more broadly.