Alfred Whitmore and the Discovery of Melioidosis

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Abstract

We review the discovery of the tropical infectious disease melioidosis by Alfred Whitmore, a pathologist from England, and his assistant from India, C.S. Krishnaswami. We discuss how the subsequent disappearance of melioidosis from the medical literature of Burma holds parallels with the current neglect and under recognition of the disease. We urge global and national public health authorities to add melioidosis to existing neglected tropical diseases surveillance systems.

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Melioidosis

W. Joost Wiersinga, Direk Limmathurotsakul, David Dance … (2018)

Burkholderia pseudomallei is a Gram-negative environmental bacterium and the aetiological agent of melioidosis, a life-threatening infection that is estimated to account for ~89,000 deaths per year worldwide. Diabetes mellitus is a major risk factor for melioidosis, and the global diabetes pandemic could increase the number of fatalities caused by melioidosis. Melioidosis is endemic across tropical areas, especially in southeast Asia and northern Australia. Disease manifestations can range from acute septicaemia to chronic infection, as the facultative intracellular lifestyle and virulence factors of B. pseudomallei promote survival and persistence of the pathogen within a broad range of cells, and the bacteria can manipulate the host’s immune responses and signalling pathways to escape surveillance. The majority of patients present with sepsis, but specific clinical presentations and their severity vary depending on the route of bacterial entry (skin penetration, inhalation or ingestion), host immune function and bacterial strain and load. Diagnosis is based on clinical and epidemiological features as well as bacterial culture. Treatment requires long-term intravenous and oral antibiotic courses. Delays in treatment due to difficulties in clinical recognition and laboratory diagnosis often lead to poor outcomes and mortality can exceed 40% in some regions. Research into B. pseudomallei is increasing, owing to the biothreat potential of this pathogen and increasing awareness of the disease and its burden; however, better diagnostic tests are needed to improve early confirmation of diagnosis, which would enable better therapeutic efficacy and survival.

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Predicted global distribution of Burkholderia pseudomallei and burden of melioidosis.

Direk Limmathurotsakul, Nick Golding, David Dance … (2016)

Burkholderia pseudomallei, a highly pathogenic bacterium that causes melioidosis, is commonly found in soil in Southeast Asia and Northern Australia(1,2). Melioidosis can be difficult to diagnose due to its diverse clinical manifestations and the inadequacy of conventional bacterial identification methods(3). The bacterium is intrinsically resistant to a wide range of antimicrobials, and treatment with ineffective antimicrobials may result in case fatality rates (CFRs) exceeding 70%(4,5). The importation of infected animals has, in the past, spread melioidosis to non-endemic areas(6,7). The global distribution of B. pseudomallei and burden of melioidosis, however, remain poorly understood. Here, we map documented human and animal cases, and the presence of environmental B. pseudomallei, and combine this in a formal modelling framework(8-10) to estimate the global burden of melioidosis. We estimate there to be 165,000 (95% credible interval 68,000-412,000) human melioidosis cases per year worldwide, of which 89,000 (36,000-227,000) die. Our estimates suggest that melioidosis is severely underreported in the 45 countries in which it is known to be endemic and that melioidosis is likely endemic in a further 34 countries which have never reported the disease. The large numbers of estimated cases and fatalities emphasise that the disease warrants renewed attention from public health officials and policy makers.

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Global burden of melioidosis in 2015: a systematic review and data synthesis

Emma Birnie, Harjeet Virk, Jelmer Savelkoel … (2019)

Melioidosis, caused by the environmental bacterium Burkholderia pseudomallei , is an often-fatal infectious disease with a high prevalence across tropical areas. Clinical presentation can vary from abscess formation to pneumonia and septicaemia. We assessed the global burden of melioidosis, expressed in disability-adjusted life years (DALYs), for the year 2015. A systematic review of the peer-reviewed literature for human melioidosis cases between 1990 and 2015 was performed. Using a broad search strategy, no language restrictions and combinations of search terms, Burkholderia spp. and disease names, all relevant articles were screened on title, abstract, and full text. Quantitative data from cases including mortality, age, sex, infectious and post-infectious sequelae, antibiotic treatment and symptom duration were extracted. This information was then combined with established disability weights and expert panel discussions to construct an incidence-based disease model. The disease model was integrated with established global incidence and mortality estimates to calculate global melioidosis DALYs. 2 888 articles were screened, of which 475 eligible studies containing quantitative information were retained. Sepsis/septic shock and pneumonia were the most common outcomes, occurring in 18.0% (1526/8469), 12.1% (1004/8298) and 35.7% (3633/10175) of patients respectively. The male to female ratio of infection was 2:1. We estimate that in 2015, the global burden of melioidosis was 4·6 million DALYs (UI 3·2-6·6) or 84·3 per 100 000 people (UI 57·5-120·0). Years of life lost (YLL) accounted for 98·9% (UI 97·7-99·5) of the total DALYs. Our estimates enable comparison with other tropical diseases which are already recognised as neglected and give policy makers the information necessary to reconsider melioidosis as a major neglected tropical disease. European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Research Grant 2018; AMC PhD Scholarship; The Netherlands Organisation for Scientific Research (NWO); H2020 Marie Skłodowska-Curie Innovative Training Network (MC-ITN) European Sepsis Academy.

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Journal

Journal ID (nlm-ta): Emerg Infect Dis

Journal ID (iso-abbrev): Emerg Infect Dis

Journal ID (publisher-id): EID

Title: Emerging Infectious Diseases

Publisher: Centers for Disease Control and Prevention

ISSN (Print): 1080-6040

ISSN (Electronic): 1080-6059

Publication date (Print): April 2024

Volume: 30

Issue: 4

Pages: 752-756

Affiliations

[1]Amsterdam UMC location University of Amsterdam, Amsterdam, the Netherlands (J. Savelkoel);

[2]Lao-Oxford-Mahosot Hospital–Wellcome Trust Research Unit, Mahosot Hospital, Vientiane, Laos (D.A.B. Dance);

[3]University of Oxford, Oxford, UK (D.A.B. Dance);

[4]London School of Hygiene & Tropical Medicine, London, UK (D.A.B. Dance)

Author notes

Address for correspondence: Jelmer Savelkoel, Amsterdam UMC location University of Amsterdam, Center for Experimental and Molecular Medicine, Meibergdreef 9, 1105 AZ, Rm T1.0-234, Amsterdam, the Netherlands; or David A.B. Dance; email: j.savelkoel@ 123456amsterdamumc.nl or david.d@ 123456tropmedres.ac

Article

Publisher ID: 23-0693

DOI: 10.3201/eid3004.230693

PMC ID: 10977855

SO-VID: 398ae28d-7980-4871-8bfa-5c0564006ee6

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Emerging Infectious Diseases is a publication of the U.S. Government. This publication is in the public domain and is therefore without copyright. All text from this work may be reprinted freely. Use of these materials should be properly cited.

Alfred Whitmore and the Discovery of Melioidosis

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Most cited references 21

Melioidosis

Predicted global distribution of Burkholderia pseudomallei and burden of melioidosis.

Global burden of melioidosis in 2015: a systematic review and data synthesis

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