Evaluation of a Rapid Diagnostic Test for Detection of Burkholderia pseudomallei in the Lao People's Democratic Republic

Abstract

Burkholderia pseudomallei causes significant global morbidity and mortality, with the highest disease burden in parts of Asia where culture-based diagnosis is often not available. We prospectively evaluated the Active Melioidosis Detect (AMD; InBios International, USA) lateral flow immunoassay (LFI) for rapid detection of B. pseudomallei in turbid blood cultures, pus, sputum, sterile fluid, urine, and sera. The performance of this test was compared to that of B. pseudomallei detection using monoclonal antibody latex agglutination (LA) and immunofluorescence assays (IFA), with culture as the gold standard. AMD was 99% (99/100; 95% confidence interval, 94.6 to 100%) sensitive and 100% (308/308; 98.8 to 100%) specific on turbid blood culture bottles, with no difference from LA or IFA. AMD specificity was 100% on pus (122/122; 97.0 to 100%), sputum (20/20; 83.2 to 100%), and sterile fluid (44/44; 92 to 100%). Sensitivity on these samples was as follows: pus, 47.1% (8/17; 23.0 to 72.2%); sputum, 33.3% (1/3; 0.84 to 90.6%); and sterile fluid, 0% (0/2; 0 to 84.2%). For urine samples, AMD had a positive predictive value of 94% (32/34; 79.7 to 98.5%) for diagnosing melioidosis in our cohort. AMD sensitivity on stored sera, collected prospectively from melioidosis cases during this study, was 13.9% (5/36; 4.7% to 29.5%) compared to blood culture samples taken on the same day. In conclusion, AMD is an excellent tool for rapid diagnosis of melioidosis from turbid blood cultures and maintains specificity across all sample types. It is a promising tool for urinary antigen detection, which could revolutionize diagnosis of melioidosis in resource-limited settings. Further work is required to improve sensitivity on nonblood culture samples.

Evaluation of the Active Melioidosis Detect™ test as a point-of-care tool for the early diagnosis of melioidosis: a comparison with culture in Laos

“…The clinical management of melioidosis could thus be improved by a POC test. This study built on our previous evaluation of the AMD, which was conducted at the same hospital, 15 but instead of using specimens passively received in the laboratory, we actively encouraged the submission of all relevant specimens (blood and urine, and sputum and pus whenever available) from suspected melioidosis patients as soon as possible after hospital admission. Using this approach we found that for patients with a positive culture, the time to presumptive diagnosis was reduced by a median of 23 h (p=0.003).…”

“…Recently, a qualitative, membrane-based lateral flow immunoassay point-of-care test (POCT) that detects the capsular polysaccharide of B. pseudomallei , the Active Melioidosis Detect™ (AMD), has been developed by InBios (Seattle, WA, USA) 13 . The AMD has undergone a small number of evaluations for the direct detection of B. pseudomallei in a range of clinical samples 12–17 as well as for the detection of the organism in blood culture broths 15 , 18 . Such a test, which is easy to use and relatively cheap, could prove a very valuable tool in resource-limited settings.…”

Antibodies in Melioidosis: The Role of the Indirect Hemagglutination Assay in Evaluating Patients and Exposed Populations

“…Enzyme-linked immunosorbent assay has the advantage of allowing focus on IgG subclasses and use of reader machines to reduce interlaboratory variation. Other approaches based on pathogen detection strategy including PCR, 58 – 60 microarray, 61 , 62 lateral flow immunoassay 63 – 66 and matrix-assisted laser desorption ionization-time-of-flight mass spectrometry 67 , 68 are also in development to confirm melioidosis diagnosis.…”

Identification of Burkholderia pseudomallei by Use of the Vitek Mass Spectrometer

“…Notably, the combination of IHA and IgM enzyme-linked immunosorbent assay (ELISA) in the diagnosis of acute melioidosis in an area of endemicity demonstrated a sensitivity of 100% and specificity of 95.4%; however, the performance of this test is variable in a low prevalence setting (14). The development of a lateral flow assay which detects capsular polysaccharide via a monoclonal antibody has a reported sensitivity of 99% and specificity of 100% when used on turbid blood cultures (15,16). The test is easy to perform, relatively inexpensive, and may be a promising rapid diagnostic tool (16).…”

“…The development of a lateral flow assay which detects capsular polysaccharide via a monoclonal antibody has a reported sensitivity of 99% and specificity of 100% when used on turbid blood cultures (15,16). The test is easy to perform, relatively inexpensive, and may be a promising rapid diagnostic tool (16). PCR testing of clinical isolates in B. pseudomallei culture-positive patients has demonstrated 100% sensitivity and specificity on wound swabs, abscess aspirates, urine, and sputum (17).…”