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      Melioidosis in lower provincial Cambodia: A case series from a prospective study of sepsis in Takeo Province

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          Abstract

          Melioidosis is a severe infectious disease caused by the gram-negative soil bacterium Burkholderia pseudomallei. Melioidosis is well known to be a major cause of morbidity and mortality in Southeast Asia, particularly in Thailand. However, melioidosis remains underreported in surrounding areas such as Cambodia. We report a case series of melioidosis in seven patients from Takeo Province, Cambodia. The patients, aged 24–65 years, were enrolled from May 2014 to May 2015 during a one year prospective study of sepsis at Takeo Provincial Hospital. They presented with fever, rigors, dyspnea, fatigue, diaphoresis, productive cough, and skin abscesses. Six of the seven patients were also hyponatremic. B. pseudomallei was cultured from the blood of six patients and the sputum of one patient. In this manuscript, we provide a detailed description of the clinical presentation, case management and laboratory confirmation of B. pseudomallei, as well as discuss the difficulties of identifying and treating melioidosis in low resource settings.

          Author summary

          In spite of the fact that Cambodia shares borders with well-known hyper-endemic areas for Burkholderia pseudomallei where thousands of melioidosis cases occur each year, only a handful of melioidosis cases have been described in Cambodia. This is due, in part, to the lack of appropriate diagnostic resources there and the fact that physicians are not familiar with the appropriate diagnostic and treatment algorithms. As a result, the true burden of melioidosis in Cambodia is drastically underestimated and confirmed cases are rarely treated properly. During a one year study of sepsis in Takeo Provincial Hospital in Takeo Province Cambodia, we enrolled 139 patients which included seven culture-confirmed cases of melioidosis. As part of our study, laboratory workups including blood gasses, blood chemistries and hematology are routinely performed as well as imaging and a detailed record of medications administered during treatment. As a result, our report describes one of the more well-characterized cohorts of adult B. pseudomallei infections from Cambodia, originating in a region that had relatively few documented cases previously. Additionally, our case series touches upon a number of challenges faced by resource-limited health systems addressing melioidosis in areas of high endemicity.

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          Most cited references47

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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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            Melioidosis.

            N. White (2003)
            Melioidosis, which is infection with the gram-negative bacterium Burkholderia pseudomallei, is an important cause of sepsis in east Asia and northern Australia. In northeastern Thailand, melioidosis accounts for 20% of all community-acquired septicaemias, and causes death in 40% of treated patients. B pseudomallei is an environmental saprophyte found in wet soils. It mostly infects adults with an underlying predisposing condition, mainly diabetes mellitus. Melioidosis is characterised by formation of abscesses, especially in the lungs, liver, spleen, skeletal muscle, and prostate. In a third of paediatric cases in southeast Asia, the disease presents as parotid abscess. In northern Australia, 4% of patients present with brain stem encephalitis. Ceftazidime is the treatment of choice for severe melioidosis, but response to high dose parenteral treatment is slow (median time to abatement of fever 9 days). Maintenance antibiotic treatment is with a four-drug regimen of chloramphenicol, doxycycline, and trimethoprim-sulfamethoxazole, or with amoxicillin-clavulanate in children and pregnant women. However, even with 20 weeks' antibiotic treatment, 10% of patients relapse. With improvements in health care and diagnostic microbiology in endemic areas of Asia, and increased travel, melioidosis will probably be recognised increasingly during the next decade.
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              Melioidosis: a clinical overview.

              Melioidosis, an infection caused by the environmental Gram-negative bacillus Burkholderia pseudomallei, has emerged as an important cause of morbidity and mortality in Southeast Asia and northern Australia. a review of the literature using PubMed. Approaches to diagnosis and antimicrobial therapy. Whether seroconversion signals the presence of a quiescent bacterial focus and an increase in long-term risk of melioidosis. Melioidosis is potentially preventable, but there is a striking lack of evidence on which to base an effective prevention programme. An accurate map defining the global distribution of B. pseudomallei is needed, together with studies on the relative importance of different routes of infection. There is a marked difference in mortality from melioidosis in high-income versus lower income countries, and affordable strategies that reduce death from severe sepsis (from any cause) in resource-restricted settings are needed.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Project administrationRole: SupervisionRole: Writing – original draftRole: Writing – review & editing
                Role: Formal analysisRole: Writing – original draftRole: Writing – review & editing
                Role: InvestigationRole: MethodologyRole: Project administrationRole: Supervision
                Role: Formal analysisRole: InvestigationRole: Supervision
                Role: InvestigationRole: Supervision
                Role: InvestigationRole: Supervision
                Role: ConceptualizationRole: InvestigationRole: MethodologyRole: Writing – review & editing
                Role: Supervision
                Role: Supervision
                Role: InvestigationRole: Supervision
                Role: InvestigationRole: MethodologyRole: SupervisionRole: Writing – review & editing
                Role: ConceptualizationRole: Formal analysisRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: Project administrationRole: SupervisionRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: Project administrationRole: SupervisionRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS Negl Trop Dis
                PLoS Negl Trop Dis
                plos
                plosntds
                PLoS Neglected Tropical Diseases
                Public Library of Science (San Francisco, CA USA )
                1935-2727
                1935-2735
                13 September 2017
                September 2017
                : 11
                : 9
                : e0005923
                Affiliations
                [1 ] Naval Medical Research Center, Biological Defense Research Directorate, Ft. Detrick, Maryland, United States of America
                [2 ] Naval Medical Research Unit-2, Phnom Penh, Cambodia
                [3 ] Cambodian Communicable Disease Control, Ministry of Health, Phnom Penh, Cambodia
                [4 ] Takeo Provincial Referral Hospital, Takeo, Cambodia
                University of Liverpool, UNITED KINGDOM
                Author notes

                The authors have declared that no competing interests exist.

                Author information
                http://orcid.org/0000-0001-5554-0133
                Article
                PNTD-D-17-00834
                10.1371/journal.pntd.0005923
                5612750
                28902844
                4e296c02-330b-4f1c-a0cf-8ac8a1d57971

                This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

                History
                : 24 May 2017
                : 1 September 2017
                Page count
                Figures: 2, Tables: 2, Pages: 15
                Funding
                Funded by: Defense Threat Reduction Agency
                Award ID: CB3967
                Award Recipient :
                Funding for this work was provided by the Defense Threat Reduction Agency (DTRA) www.dtra.mil Award CB3967 The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                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
                People and Places
                Geographical Locations
                Asia
                Cambodia
                Medicine and Health Sciences
                Diagnostic Medicine
                Signs and Symptoms
                Sepsis
                Medicine and Health Sciences
                Pathology and Laboratory Medicine
                Signs and Symptoms
                Sepsis
                Medicine and Health Sciences
                Diagnostic Medicine
                Signs and Symptoms
                Fevers
                Medicine and Health Sciences
                Pathology and Laboratory Medicine
                Signs and Symptoms
                Fevers
                Medicine and Health Sciences
                Pharmacology
                Drugs
                Antimicrobials
                Antibiotics
                Biology and Life Sciences
                Microbiology
                Microbial Control
                Antimicrobials
                Antibiotics
                Medicine and Health Sciences
                Pulmonology
                Dyspnea
                Biology and Life Sciences
                Anatomy
                Body Fluids
                Mucus
                Sputum
                Medicine and Health Sciences
                Anatomy
                Body Fluids
                Mucus
                Sputum
                Biology and Life Sciences
                Physiology
                Body Fluids
                Mucus
                Sputum
                Medicine and Health Sciences
                Physiology
                Body Fluids
                Mucus
                Sputum
                Custom metadata
                vor-update-to-uncorrected-proof
                2017-09-25
                All relevant data are within the paper and its Supporting Information files.

                Infectious disease & Microbiology
                Infectious disease & Microbiology

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