Mycobacterium ulcerans DNA Not Detected in Faecal Samples from Buruli Ulcer Patients: Results of a Pilot Study

It has recently been shown that in a Buruli ulcer (BU) endemic region of southeastern Australia, significant numbers of possums (native tree-dwelling marsupials) have clinical BU disease. Furthermore, based on quantitative PCR (qPCR) analysis, animals with BU lesions (and some without) shed M. ulcerans DNA in their faeces, indicative of bacterial loads of up to 108 organisms/gram. These findings led us to propose that humans might also harbour M. ulcerans in their gastrointestinal tract and shed the bacterium in their faeces. We conducted a pilot study and collected faecal swabs from 26 patients with confirmed BU and 31 healthy household controls. Faecal samples were also collected from 10 healthy controls from non-endemic regions in Ghana. All 67 specimens were negative when tested by IS2404 PCR. The detection sensitivity of this method was ≥104 bacteria per gram (wet-weight) of human faecal material. We conclude that the human gastrointestinal tract is unlikely to be a significant reservoir of M. ulcerans

A Genomic Approach to Resolving Relapse versus Reinfection among Four Cases of Buruli Ulcer

YesBackground. Increased availability of Next Generation Sequencing (NGS) techniques allows, for the first time, to distinguish relapses from reinfections in patients with multiple Buruli ulcer (BU) episodes. Methodology. We compared the number and location of single nucleotide polymorphisms (SNPs) identified by genomic screening between four pairs of Mycobacterium ulcerans isolates collected at the time of first diagnosis and at recurrence, derived from a collection of almost 5000 well characterized clinical samples from one BU treatment center in Benin. Principal Findings. The findings suggest that after surgical treatment—without antibiotics—the second episodes were due to relapse rather than reinfection. Since specific antibiotics were introduced for the treatment of BU, the one patient with a culture available from both disease episodes had M. ulcerans isolates with a genomic distance of 20 SNPs, suggesting the patient was most likely reinfected rather than having a relapse. Conclusions. To our knowledge, this study is the first to study recurrences in M. ulcerans using NGS, and to identify exogenous reinfection as causing a recurrence of BU. The occurrence of reinfection highlights the contribution of ongoing exposure to M. ulcerans to disease recurrence, and has implications for vaccine development.This work was supported by the UBS Optimus Foundation (Zurich, Switzerland) and the Department of Economy, Science and Innovation of the Flemish Government (Belgium). KV was supported by a VLADOC PhD scholarship of VLIRUOS (Belgium)

Laboratory diagnosis of Buruli ulcer : challenges and future perspectives

Current options to control Buruli ulcer (BU) are limited, as no effective vaccine is available and knowledge on transmission mechanisms of the causative agent, Mycobacterium ulcerans, is incomplete. Early case detection and rapid initiation of treatment are key elements to prevent the development of large, disfiguring ulcers often associated with permanent physical disability and stigma. BU has been reported from 34 countries, with the greatest disease burden in West Africa and steadily increasing case numbers in south-eastern Australia. The disease can present in a variety of clinical manifestations, including relatively unspecific, painless nodules, plaques, and edema, which may eventually progress to chronic, ulcerative lesions. The clinical diagnosis of BU is therefore complicated by a broad differential diagnosis, particularly in tropical areas, where the prevalence of other skin conditions with a similar appearance is high. With the introduction of combination antibiotic therapy, replacing excision surgery as the standard treatment for BU, pre-treatment confirmation of the clinical diagnosis has further gained in importance to avoid the redundant use of anti-mycobacterial drugs. At present, available confirmatory diagnostic tests either lack sufficient sensitivity/specificity or are centralized and thus often not accessible to patients living in remote, rural areas of Africa. In recognition of this disparity, WHO and other stakeholders have called for new diagnostic tools for BU that can be applied at district hospitals or primary healthcare facilities. This chapter highlights challenges, advances and future prospects for the necessary decentralization of the diagnosis of BU

Buruli ulcer : history and disease burden

A major objective of this open access book is to summarize the current status of Buruli Ulcer (BU) research for the first time. It will identify gaps in our knowledge, stimulate research and support control of the disease by providing insight into approaches for surveillance, diagnosis, and treatment of Buruli Ulcer. Book chapters will cover the history, epidemiology diagnosis, treatment and disease burden of BU and provide insight into the microbiology, genomics, transmission and virulence of Mycobacterium ulcerans. ; Supports further investigation by summarizing state of the art in the field of Buruli ulcer research Enriches understanding of epidemiology of Buruli ulcer in different geographic regions Reviews exhaustively the characteristics of Mycobacterium ulcerans diseas