Yersinia Pestis Lateral Flow Immunoassay for Blood Samples

Overview

Plague is a deadly but highly treatable disease caused by the bacterium Y. pestis. Due to the historical development of Y. pestis as a bioweapon by several nation states, it is listed by the US as a potential bioweapon that could be used against US warfighters. Although this bacterium is ecologically established worldwide, it mostly affects impoverished people who live in rural low-resource areas of Madagascar. Plague is acquired directly from bites of infected fleas but, if left untreated, it can progress to the highly lethal pneumonic form that can result in human to human transmission. With the dangers of pneumonic plague in the context of both natural outbreak and as a bioweapon used against warfighter, the goal of this study is to investigate a diagnostic test that is able to rapidly and locally diagnose this disease in low-resource settings. This study aims to evaluate a US-developed new LFI (Lateral Flow Immunoassay) assay intended for capillary blood (finger-prick) to diagnose humans infected with Y. pestis. The investigators will rigorously validate with assay on human populations from active plague sites and correlate the results with the results of paired clinical samples used in standard medical workup using existing diagnostics tests.

The purpose of this study will be to generate the data required to thoroughly validate the ability of plague LFI assay (Lateral Flow Immunoassay) to accurately diagnose human infections with Y. pestis. These validation data will eventually be presented to US Food and Drug Administration (FDA; along with data from other studies that NAU will not participate) to seek approval for commercial license. The objective will be to validate this assay on the capillary blood of humans suspected to have plague as well as a study cohort likely to not have plague. From the suspected population; the specific aims of this study are to enroll up to 300 participants who present clinical signs of illness based on specific inclusion criteria. We will collect two types of blood samples from enrolled participants 1) capillary blood from a finger prick and 2) venous blood. The capillary blood will be used for direct testing on the LFI assay and the venous blood will be used to perform independent validations. This study is designed as a correlation study to understand 1) how LFI assay results compare with results from traditional diagnostic methods based on DNA detection methods and bacterial culture isolate on bubo aspirate or sputum and 2) effectiveness of capillary blood to serve as a diagnostic clinical sample as compared with traditional biological samples (venous blood, bubo and sputum). The study is designed to evaluate the outcome of LFI and how LFI results correlate with the standard plague diagnostics methods used in Madagascar and other methods. We are not examining the relationship between the results of the LFI and health outcomes of the participants. Decision of participant's medical treatment is solely based on the clinical judgment of the physician and guidelines set forth by Madagascar National Plague Control Program (PNLP); no formal test is involved with medical decision. All participants who are tested by LFI will have received medical treatment prior to the start of the study and the continuation of their medical treatment is guided by PNLP and physician judgment only. Again, we are not looking at the relationship between the results of the LFI and health outcomes of the participants. From the non-suspect cohort, greater detail will be provided as obtained. In brief, this subject population will consist of active duty US Naval personnel and DoD beneficiaries presenting to participating study sites in the United States with influenza-like symptoms (fever, cough, sore throat). Since the US is non-endemic for plague, all participants will be presumed to be negative for Y. pestis.