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      Melioidosis in Malaysia: Incidence, Clinical Challenges, and Advances in Understanding Pathogenesis

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          Abstract

          Malaysia is an endemic hot spot for melioidosis; however, a comprehensive picture of the burden of disease, clinical presentations, and challenges faced in diagnosis and treatment of melioidosis is not available. This review provides a nonexhaustive overview of epidemiological data, clinical studies, risk factors, and mortality rates from available literature and case reports. Clinical patterns of melioidosis are generally consistent with those from South and Southeast Asia in terms of common primary presentations with diabetes as a major risk factor. Early diagnosis and appropriate management of Malaysian patients is a key limiting factor, which needs to be addressed to reduce serious complications and high mortality and recurrence rates. Promoting awareness among the local healthcare personnel is crucial to improving diagnostics and early treatment, as well as educating the Malaysian public on disease symptoms and risk factors. A further matter of urgency is the need to make this a notifiable disease and the establishment of a national melioidosis registry. We also highlight local studies on the causative agent, Burkholderia pseudomallei, with regards to bacteriology and identification of virulence factors as well as findings from host–pathogen interaction studies. Collectively, these studies have uncovered new correlations and insights for further understanding of the disease.

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          Most cited references83

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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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            Multilocus sequence typing and evolutionary relationships among the causative agents of melioidosis and glanders, Burkholderia pseudomallei and Burkholderia mallei.

            A collection of 147 isolates of Burkholderia pseudomallei, B. mallei, and B. thailandensis was characterized by multilocus sequence typing (MLST). The 128 isolates of B. pseudomallei, the causative agent of melioidosis, were obtained from diverse geographic locations, from humans and animals with disease, and from the environment and were resolved into 71 sequence types. The utility of the MLST scheme for epidemiological investigations was established by analyzing isolates from captive marine mammals and birds and from humans in Hong Kong with melioidosis. MLST gave a level of resolution similar to that given by pulsed-field gel electrophoresis and identified the same three clones causing disease in animals, each of which was also associated with disease in humans. The average divergence between the alleles of B. thailandensis and B. pseudomallei was 3.2%, and there was no sharing of alleles between these species. Trees constructed from differences in the allelic profiles of the isolates and from the concatenated sequences of the seven loci showed that the B. pseudomallei isolates formed a cluster of closely related lineages that were fully resolved from the cluster of B. thailandensis isolates, confirming their separate species status. However, isolates of B. mallei, the causative agent of glanders, recovered from three continents over a 30-year period had identical allelic profiles, and the B. mallei isolates clustered within the B. pseudomallei group of isolates. Alleles at six of the seven loci in B. mallei were also present within B. pseudomallei isolates, and B. mallei is a clone of B. pseudomallei that, on population genetics grounds, should not be given separate species status.
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              Endemic melioidosis in tropical northern Australia: a 10-year prospective study and review of the literature.

              In a prospective study of melioidosis in northern Australia, 252 cases were found over 10 years. Of these, 46% were bacteremic, and 49 (19%) patients died. Despite administration of ceftazidime or carbapenems, mortality was 86% (43 of 50 patients) among those with septic shock. Pneumonia accounted for 127 presentations (50%) and genitourinary infections for 37 (15%), with 35 men (18%) having prostatic abscesses. Other presentations included skin abscesses (32 patients; 13%), osteomyelitis and/or septic arthritis (9; 4%), soft tissue abscesses (10; 4%), and encephalomyelitis (10; 4%). Risk factors included diabetes (37%), excessive alcohol intake (39%), chronic lung disease (27%), chronic renal disease (10%), and consumption of kava (8%). Only 1 death occurred among the 51 patients (20%) with no risk factors (relative risk, 0.08; 95% confidence interval, 0.01-0.58). Intensive therapy with ceftazidime or carbapenems, followed by at least 3 months of eradication therapy with trimethoprim-sulfamethoxazole, was associated with decreased mortality. Strategies are needed to decrease the high mortality with melioidosis septic shock. Preliminary data on granulocyte colony-stimulating factor therapy are very encouraging.

                Author and article information

                Journal
                Trop Med Infect Dis
                Trop Med Infect Dis
                tropicalmed
                Tropical Medicine and Infectious Disease
                MDPI
                2414-6366
                27 February 2018
                March 2018
                : 3
                : 1
                : 25
                Affiliations
                [1 ]School of Biosciences and Biotechnology, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, Bangi 43600, Malaysia; sylvia@ 123456ukm.edu.my
                [2 ]Emergency Department, Pantai Hospital Ipoh, 31400 Ipoh, Malaysia; paulkvijay@ 123456gmail.com
                [3 ]Department of Paediatrics, Bintulu Hospital, Bintulu 97000, Malaysia; anand_bintulu@ 123456yahoo.com
                [4 ]Institute of Health and Community Medicine, Universiti Malaysia Sarawak, Kota Samarahan 94300, Malaysia; pyuwana@ 123456unimas.my (Y.P.); monghowooi@ 123456gmail.com (M.-H.O.)
                [5 ]Department of Paediatrics, Sarawak General Hospital, Kuching 93586, Malaysia
                [6 ]Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur 50603, Malaysia; vanitha.ma@ 123456gmail.com (V.M.); kumuthamalar@ 123456um.edu.my (K.M.V.); jamuna@ 123456ummc.edu.my (J.V.)
                [7 ]Department of Pathobiology and Medical Diagnostics, Faculty of Medicine and Health Science, Universiti Malaysia Sabah, Kota Kinabalu 88400, Malaysia; sylviadaim@ 123456ums.edu.my
                [8 ]Department of Internal Medicine, Kulliyyah of Medicine, International Islamic University Malaysia, Kuantan 25200, Malaysia
                Author notes
                [* ]Correspondence: sheila@ 123456ukm.edu.my (S.N.); how_sh@ 123456yahoo.com (S.-H.H.); Tel.: +60-389213862 (S.N.); +60-199171970 (S.-H.H.)
                Author information
                https://orcid.org/0000-0002-2132-2346
                https://orcid.org/0000-0002-6521-6641
                https://orcid.org/0000-0001-6796-9885
                Article
                tropicalmed-03-00025
                10.3390/tropicalmed3010025
                6136604
                30274422
                7db1b075-efac-48f8-abdd-2ebdf22d00ec
                © 2018 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 09 January 2018
                : 18 February 2018
                Categories
                Review

                melioidosis,burkholderia pseudomallei,malaysia,epidemiology,bacteriology

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