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      Performance evaluation of Active Melioidosis Detect-Lateral Flow Assay (AMD-LFA) for diagnosis of melioidosis in endemic settings with limited resources

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          Abstract

          Melioidosis is a fatal infection caused by the soil saprophyte Burkholderia pseudomallei. Early diagnosis and befitting medical management can significantly influence the clinical outcomes among patients with melioidosis. Witnessing an annual increment in the number of melioidosis cases, over the past few years, mainly from the developing tropical nations, the present study was undertaken to evaluate the diagnostic utility of Active Melioidosis Detect TMLateralFlow Assay (AMD-LFA), in comparison with enrichment culture and PCR. A total of 206clinical specimens obtained from 175 patients with clinical suspicion of melioidosis were considered for the evaluation. Positivity for B. pseudomallei using enrichment culture, PCR and AMD-LFA were observed among 63 (30.5%), 55 (26.6%) and 63 (30.5%) specimens respectively. The AMD-LFA failed to detect melioidosis from 9 culture-confirmed cases (6 whole blood specimens, 2 pus samples, and one synovial fluid). Further the test gave faint bands from 9 urine samples which were negative by culture and PCR. AMD-LFA demonstrated a sensitivity, specificity, of 85.71%(CI:74.61% to 93.25%) and 93.62% (CI:88.23% to 97.04%), with positive predictive value of 85.71% (CI: 75.98% to 91.92%) and negative predictive value of 93.62% (CI:88.89% to 96.42%). The test needs further evaluation in view of the faint bands from negative urine samples, for incorporating the test as a point of care assay.In view of its rapidity and ease of testing AMD-LFA might be useful in early diagnosis of melioidosis at resource constraint settings.

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          Increasing Incidence of Human Melioidosis in Northeast Thailand

          Melioidosis is a serious community-acquired infectious disease caused by the Gram-negative environmental bacterium Burkholderia pseudomallei. A prospective cohort study identified 2,243 patients admitted to Sappasithiprasong Hospital in northeast Thailand with culture-confirmed melioidosis between 1997 and 2006. These data were used to calculate an average incidence rate for the province of 12.7 cases of melioidosis per 100,000 people per year. Incidence increased incrementally from 8.0 (95% confidence interval [CI] = 7.2–10.0) in 2000 to 21.3 (95% CI = 19.2–23.6) in 2006 (P < 0.001; χ2 test for trend). Male sex, age ≥ 45 years, and either known or undiagnosed diabetes were independent risk factors for melioidosis. The average mortality rate from melioidosis over the study period was 42.6%. The minimum estimated population mortality rate from melioidosis in 2006 was 8.63 per 100,000 people (95% CI = 7.33–10.11), the third most common cause of death from infectious diseases in northeast Thailand after human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) and tuberculosis.
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            The epidemiology of melioidosis in Australia and Papua New Guinea.

            Melioidosis was first described in Australia in an outbreak in sheep in 1949 in north Queensland (22 degrees S). Human melioidosis was first described from Townsville (19 degrees S) in 1950. Melioidosis is hyperendemic in the Top End of the Northern Territory (NT) and as in parts of northeastern Thailand it is the commonest cause of fatal community-acquired septicemic pneumonia. In the 9 years since 1989 the prospective NT melioidosis study at Royal Darwin Hospital (12 degrees S) has documented 206 culture confirmed cases of melioidosis, with an average annual incidence of 16.5/100,000. Melioidosis is also seen in the north of Western Australia and north Queensland, including the Torres Strait Islands, but is uncommon in adjacent Papua New Guinea. Serological studies suggest that infection is rare in the Port Moresby region, but there is emerging evidence of melioidosis from Western Province. The NT study has documented inoculating events in 52 (25%) of cases, with an incubation period of 1-21 days (mean 9 days); 84% of cases had acute disease from presumed recent acquisition and 13% had chronic disease (sick, > 2 months). In 4% there was evidence of possible reactivation from a latent focus; 28 of 153 (18%) males had prostatic abscesses. The overall mortality was 21% (43 cases), with a mortality rate in septicemic cases (95) of 39% and in non-septicemic cases (103) of 4%. Pneumonia was the commonest presentation in both groups and, in addition, eight patients (two deaths) presented with melioidosis encephalomyelitis. Melioidosis clusters in temperate Australia are attributed to animals imported from the north. Molecular typing of Burkholderia pseudomallei isolates from temperate southwest Western Australia showed clonality over 25 years. In this outbreak and in studies from the NT, some soil isolates are molecularly identical to epidemiologically related animal and human isolates. Molecular typing has implicated the water supply in two clonal outbreaks in remote aboriginal communities in northern Australia. Further prospective collaborative studies are required to evaluate whether there are truly regional differences in clinical features of melioidosis and to better understand how B. pseudomallei is acquired from the environment.
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              Melioidosis Diagnostic Workshop, 20131

              Melioidosis is a severe disease that can be difficult to diagnose because of its diverse clinical manifestations and a lack of adequate diagnostic capabilities for suspected cases. There is broad interest in improving detection and diagnosis of this disease not only in melioidosis-endemic regions but also outside these regions because melioidosis may be underreported and poses a potential bioterrorism challenge for public health authorities. Therefore, a workshop of academic, government, and private sector personnel from around the world was convened to discuss the current state of melioidosis diagnostics, diagnostic needs, and future directions.

                Author and article information

                Contributors
                Role: Data curationRole: Formal analysisRole: Writing – original draft
                Role: Data curationRole: Formal analysisRole: Writing – review & editing
                Role: ConceptualizationRole: Writing – review & editingRole: Validation
                Role: ConceptualizationRole: Methodology
                Role: ConceptualizationRole: SupervisionRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                26 March 2018
                2018
                : 13
                : 3
                : e0194595
                Affiliations
                [1 ] Dept. of Microbiology, Kasturba Medical College, Manipal University, Manipal, India
                [2 ] Manipal Center for Virus Research, Manipal University, Manipal, India
                [3 ] Dept. of Molecular Microbiology and Immunology, University of Nevada, Reno, Nevada, United States of America
                Tulane University School of Medicine, UNITED STATES
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Author information
                http://orcid.org/0000-0003-0402-1143
                Article
                PONE-D-17-38470
                10.1371/journal.pone.0194595
                5868802
                29579128
                a30366d3-a2b8-4e88-b8e2-6abcdd000cee
                © 2018 Shaw et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 31 October 2017
                : 6 March 2018
                Page count
                Figures: 2, Tables: 2, Pages: 7
                Funding
                The authors received no specific funding for this work.
                Categories
                Research Article
                Medicine and Health Sciences
                Infectious Diseases
                Bacterial Diseases
                Melioidosis
                Biology and Life Sciences
                Anatomy
                Body Fluids
                Blood
                Medicine and Health Sciences
                Anatomy
                Body Fluids
                Blood
                Biology and Life Sciences
                Physiology
                Body Fluids
                Blood
                Medicine and Health Sciences
                Physiology
                Body Fluids
                Blood
                Research and Analysis Methods
                Biological Cultures
                Cell Culturing Techniques
                Enrichment Culture
                Biology and Life Sciences
                Anatomy
                Body Fluids
                Urine
                Medicine and Health Sciences
                Anatomy
                Body Fluids
                Urine
                Biology and Life Sciences
                Physiology
                Body Fluids
                Urine
                Medicine and Health Sciences
                Physiology
                Body Fluids
                Urine
                Medicine and Health Sciences
                Diagnostic Medicine
                Biology and Life Sciences
                Anatomy
                Body Fluids
                Medicine and Health Sciences
                Anatomy
                Body Fluids
                Biology and Life Sciences
                Physiology
                Body Fluids
                Medicine and Health Sciences
                Physiology
                Body Fluids
                Biology and Life Sciences
                Anatomy
                Body Fluids
                Synovial Fluid
                Medicine and Health Sciences
                Anatomy
                Body Fluids
                Synovial Fluid
                Biology and Life Sciences
                Physiology
                Body Fluids
                Synovial Fluid
                Medicine and Health Sciences
                Physiology
                Body Fluids
                Synovial Fluid
                People and Places
                Geographical Locations
                Asia
                India
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                All relevant data are within the paper.

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