Laboratory Diagnosis of Buruli Ulcer: Challenges and Future Perspectives

Röltgen, Katharina; Cruz, Israel; Ndung’u, Joseph Mathu; Pluschke, Gerd

doi:10.1007/978-3-030-11114-4_10

Cited by 17 publications

(23 citation statements)

References 84 publications

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“…This has enabled early treatment and improved patient outcomes and passive surveillance towards the control and elimination in endemic countries. Buruli ulcer, the debilitating skin-eating infection, can now be treated more effectively, and the prospects for new RDTs and point of care tests [ 11 ] would enhance early diagnosis and improved treatment outcomes for patients, and mapping towards control activities. However, for many NTDs, their control, elimination, and post-elimination surveillance require diagnostics with better performance, and the unmet diagnostic needs and lack of investment represent significant challenges in achieving these goals.…”

Section: Funding For Ntd Diagnosticsmentioning

confidence: 99%

Diagnosis of neglected tropical diseases during and after the COVID-19 pandemic

et al. 2020

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NTDs represent a group of 20 diseases that affect more than 1 billion people in 149 countries, with the vast majority in Africa, Asia, and the Americas [3]. They represent ancient diseases of stigma and poverty, primarily affecting the poor, vulnerable, and marginalised people in society, causing significant socioeconomic losses to affected individuals, families, communities, and countries, amounting to billions of dollars every year. Overall, NTDs are responsible for more than 500,000 deaths every year [4]. For the past 20 years, these diseases have been the target of various control or elimination efforts, increasing in number, size, and scope. The NTD movement has evolved and gained momentum, starting from the United Nations Millennium Development Goals, the Berlin meetings in 2003 and 2005, the 2012 London Declaration, the World Health Assembly Resolution of 2013 calling on WHO member states to intensify efforts to address NTDs, to the Sustainable Development Goals in 2015 [5]. These initiatives have sought to bring attention to diseases that for a long time have been overshadowed by more prominent diseases such as HIV/AIDS, tuberculosis (TB), and malaria, with the aim of 'leaving no one behind' [6]. On 30 January 2020, more than 350 partners around the world came together to celebrate the first ever World NTD Day to highlight the progress made and take action to beat NTDs 'for good and for all'. On 9 April 2020, the WHO released the new road map for NTDs 2021-2030, which would have been considered for approval by the Seventythird World Health Assembly (WHA) [7], were the proceedings not delayed due to the COVID-19 pandemic. The road map lays out the basis for the control and/or elimination of NTDs over the next 10 years, and highlights that 'effective diagnostics are a prerequisite for reaching the 2030 disease targets, as they are essential key components of NTD programmes, PLOS NEGLECTED TROPICAL DISEASES

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Section: Funding For Ntd Diagnosticsmentioning

confidence: 99%

Diagnosis of neglected tropical diseases during and after the COVID-19 pandemic

et al. 2020

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“…Laboratory tests routinely used for confirmation of clinical diagnosis include primarily the microscopic detection of acid-fast bacilli (AFB) and M. ulcerans-specific PCR tests. While microscopy-the only diagnostic test that can currently be performed routinely at hospital level-has limited sensitivity, PCR detecting the insertion sequence IS2404 is highly sensitive and specific [13]. However, PCR requires sophisticated laboratory infrastructure and well-trained personnel and is not reliable without strict quality control [14].…”

Section: Introductionmentioning

confidence: 99%

“…In resource-poor BU endemic countries, the test is only available at a few reference centres, which poses major logistical problems. Therefore, there is urgent need for a simple and rapid diagnostic test for BU that can be performed at local hospital level or in the field [ 13 ]. Mycolactone represents an ideal target for such an assay, since it seems to be unique to M .…”

Section: Introductionmentioning

confidence: 99%

Development of an ELISA for the quantification of mycolactone, the cytotoxic macrolide toxin of Mycobacterium ulcerans

et al. 2020

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Mycolactones, macrolide cytotoxins, are key virulence factors of Mycobacterium ulcerans, the etiological agent of the chronic necrotizing skin disease Buruli ulcer. There is urgent need for a simple point-of-care laboratory test for Buruli ulcer and mycolactone represents a promising target for the development of an immunological assay. However, for a long time, all efforts to generate mycolactone-specific antibodies have failed. By using a protein conjugate of a truncated non-toxic synthetic mycolactone derivative, we recently described generation of a set of mycolactone-specific monoclonal antibodies. Using the first mycolactonespecific monoclonal antibodies that we have described before, we were able to develop an antigen competition assay that detects mycolactones. By the systematic selection of a capturing antibody and a reporter molecule, and the optimization of assay conditions, we developed an ELISA that detects common natural variants of mycolactone with a limit of detection in the low nanomolar range. The mycolactone-specific ELISA described here will be a very useful tool for research on the biology of this macrolide toxin. After conversion into a simple point-of-care test format, the competition assay may have great potential as laboratory assay for both the diagnosis of Buruli ulcer and for the monitoring of treatment efficacy.

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“…Due to the wide spectrum of BU disease manifestations and the high prevalence of skin conditions with similar presentations (particularly in tropical BU endemic regions), the clinical diagnosis of BU is not always straightforward. PCR tests targeting the IS2404 element of M. ulcerans are currently the gold standard for laboratory diagnosis of BU [7]. Swab samples from ulcers and fine needle aspirates from closed lesions are used for laboratory testing.…”

Section: Diagnosis In Reference Laboratories and At The Point Of Carementioning

confidence: 99%

“…A good understanding of the mechanisms of immune evasion is of key importance for the development of vaccines, rapid diagnostic tests (RDTs), and efficient treatment regimens. Both leprosy and BU patients develop early skin symptoms, often overlooked by patients and misdiagnosed by untrained clinicians [7,8]. Lack of point of care diagnostic tests often hinders diagnosis in early disease stages, which is crucial to prevent the disabling and stigmatizing long-term effects Katharina Röltgen, Gerd Pluschke, John Stewart Spencer, Patrick Joseph Brennan and Charlotte Avanzi contributed equally to this work.…”

Section: Introductionmentioning

confidence: 99%

The immunology of other mycobacteria: M. ulcerans, M. leprae

et al. 2020

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Mycobacterial pathogens can be categorized into three broad groups: Mycobacterium tuberculosis complex causing tuberculosis, M. leprae and M. lepromatosis causing leprosy, and atypical mycobacteria, or non-tuberculous mycobacteria (NTM), responsible for a wide range of diseases. Among the NTMs, M. ulcerans is responsible for the neglected tropical skin disease Buruli ulcer (BU). Most pathogenic mycobacteria, including M. leprae, evade effector mechanisms of the humoral immune system by hiding and replicating inside host cells and are furthermore excellent modulators of host immune responses. In contrast, M. ulcerans replicates predominantly extracellularly, sheltered from host immune responses through the cytotoxic and immunosuppressive effects of mycolactone, a macrolide produced by the bacteria. In the year 2018, 208,613 new cases of leprosy and 2713 new cases of BU were reported to WHO, figures which are notoriously skewed by vast underreporting of these diseases.

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Laboratory Diagnosis of Buruli Ulcer: Challenges and Future Perspectives

Cited by 17 publications

References 84 publications

Diagnosis of neglected tropical diseases during and after the COVID-19 pandemic

Diagnosis of neglected tropical diseases during and after the COVID-19 pandemic

Development of an ELISA for the quantification of mycolactone, the cytotoxic macrolide toxin of Mycobacterium ulcerans

The immunology of other mycobacteria: M. ulcerans, M. leprae

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