Antigen Detection Assay for Diagnosis of Melioidosis

This study will be conducted in endemic sites in which patients presenting with symptoms consistent with a diagnosis of melioidosis will be enrolled. Melioidosis symptoms include but are not limited to pneumonia, septicemia, fever, shortness of breath, chest pain, abdominal discomfort, muscle or joint pain, and skin infection with pain, swelling, or ulceration. The inclusion criteria have a full list of symptoms.

After signing informed consent and if eligible for the study, subjects will have up to 4 types of samples collected for AMD testing: 1) blood for serum, 2) urine, 3) sputum and 4) fluid (pus) from skin wound, organ abscess, or infected joint. It is expected that all subjects will have serum and urine samples. Sputum or pus may be collected if available via the standard of care from each subject. The collection and preparation of the specimens for AMD testing will be performed in accordance with the Instructions for Use and the Study Procedures Manual. All of these samples will undergo AMD testing as soon as possible after collection. In addition, archival melioidosis positive specimens of each of the 4 types of samples will be introduced into the study in a blinded manner during the prospective sample collection for AMD testing to ensure the target numbers of reference test positive specimens are achieved.

Samples for reference testing (bacterial culture and positive Burkholderia pseudomalleiidentification) will be collected at two-time points. In addition to the first time point when samples are collected for AMD testing, hospitalized subjects who have not been treated with ceftazidime or meropenem, antibiotics targeting B. pseudomallei, will also be asked to provide a second set of samples for reference testing from 3 to 6 days after the first sample collection. All specimens from both time points will be used for reference testing consisting of culture and B. pseudomallei identification. Samples for reference testing include from all subjects: 1) whole blood, 2) urine, and 3) throat swab. If available, the same pus and sputum specimens that were collected for AMD testing can be used for reference testing at the first time point. In addition, any standard of care pleural effusion and rectal swab specimens that were collected from a subject will also have reference testing performed. Reference testing includes culture and identification using clinical microbiology laboratory standard operating procedures (SOPs) appropriate for the culture and identification of B. pseudomallei.

A 2 x 2 table will be constructed foreach sample type and used to calculate the PPA and NPA of the AMD Test versusthe reference tests. The number and percentages of true positives, truenegatives, false positives, and false negatives separately by sample type. PPAand NPA will be presented by sample type along with two-sided exact (binomial –Clopper Pearson) 95% confidence intervals (CI). Subject’s gender and diseasesymptoms present on the day of testing will be presented as numbers andpercentages. Subject’s age and days post symptom onset will be presented assummary statistics by mean, standard deviation, and range. The number ofsubjects with pre-specified medical history terms will be summarized as countsand percentages by term. Other medical history findings will be presented in alisting. Body temperature will be presented as summary statistics.