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The Pan African Medical Journal Aug 2013Buruli ulcer (BU) is a cutaneous neglected tropical disease caused by Mycobacterium ulcerans. Synthesizing the evidence on their efficacy of antibiotic in the management... (Review)
Review
Buruli ulcer (BU) is a cutaneous neglected tropical disease caused by Mycobacterium ulcerans. Synthesizing the evidence on their efficacy of antibiotic in the management of BU can help to better define their roles, identify weaknesses and inform clinicians on relevant measures than can be used to control BU. Our objectives is to assess the clinical efficacy of Rifampicin-Streptomycin given for 8 weeks of treatment of early M. ulcerans infection. We searched the following electronic databases from January 2005 to July 2012: Medline, EMBASE (Excerpta Medica Database), The Cochrane Library, Google Scholar, CINAHL (Cumulative Index to Nursing and Allied Health Literature), WHOLIS (World Health Organization Library Database), LILACS (Latin American and Caribbean Literature on Health Sciences) and contacted experts in the field. There were no restrictions to language or publication status. All study designs that could provide the information we sought for were eligible provided the studies were conducted in the third world. Critical appraisal of all identified citations was done independently by three authors to establish the possible relevance of the articles for inclusion in the review. Of the 115 studies, 09 papers met the inclusion criteria. The duration of treatment ranged from 8 to 48 weeks depending on the severity. Oral chemotherapy alone obtained a curative rate of 50%. The "dual" mode of treatment (surgery + chemotherapy) reduced hospital admission period from 90 to 39.8 days, that's to 44.2%. This treatment for early stages could therefore replace surgery and in severe cases, is an indispensable aid before surgery. These results confirmed that the daily administration of Rifampicin and Streptomycin is an effective treatment for M. ulcerans infection in an early stage. Subsequent systematic reviews should be conducted to determine if antibiotics could heal injuries without resorting to surgery and to compare different treatment durations.
Topics: Administration, Oral; Drug Therapy, Combination; Hospitalization; Humans; Mycobacterium Infections, Nontuberculous; Mycobacterium ulcerans; Rifampin; Streptomycin; Surgical Procedures, Operative; Treatment Outcome
PubMed: 24396561
DOI: 10.11604/pamj.2013.15.155.2341 -
Cellular and Molecular Life Sciences :... Jul 2014Skin ulcers are most commonly due to circulatory or metabolic disorders and are a major public health concern. In developed countries, chronic wounds affect more than 1... (Review)
Review
Skin ulcers are most commonly due to circulatory or metabolic disorders and are a major public health concern. In developed countries, chronic wounds affect more than 1 % of the population and their incidence is expected to follow those observed for diabetes and obesity. In tropical and subtropical countries, an additional issue is the occurrence of ulcers of infectious origins with diverse etiologies. While the severity of cutaneous Leishmaniasis correlates with protective immune responses, Buruli ulcers caused by Mycobacterium ulcerans develop in the absence of major inflammation. Based on these two examples, this review aims to demonstrate how studies on microorganism-provoked wounds can provide insight into the molecular mechanisms controlling skin integrity. We highlight the potential interest of a mouse model of non-inflammatory skin ulceration caused by intradermal injection of mycolactone, an original lipid toxin with ulcerative and immunosuppressive properties produced by M. ulcerans.
Topics: Animals; Humans; Immunity, Active; Leishmania; Macrolides; Mice; Mycobacterium ulcerans; Skin Ulcer
PubMed: 24445815
DOI: 10.1007/s00018-014-1561-z -
Japanese Journal of Infectious Diseases 2013Buruli ulcer (BU) is an emerging human disease caused by Mycobacterium ulcerans, which mainly affects the extremities. It is most endemic in sub-Saharan Africa; however,... (Review)
Review
Buruli ulcer (BU) is an emerging human disease caused by Mycobacterium ulcerans, which mainly affects the extremities. It is most endemic in sub-Saharan Africa; however, it has been reported worldwide, including in some non-tropical areas. "M. ulcerans subsp. shinshuense" is proposed as a subspecies of M. ulcerans, which have been reported from Japan and China. A total of 35 BU cases have been reported as of November 2012. Although M. ulcerans is categorized as nontuberculous mycobacteria, it has some unique characteristics that could only be observed in this bacterium. It possesses a giant virulent plasmid, composed of 174-kbp nucleotides, coding polyketide synthase to produce macrolide toxin called mycolactone. The discovery of such a linkage of plasmid and its pathogenesis has not been reported in other human disease-causing mycobacteria.
Topics: Africa South of the Sahara; Buruli Ulcer; China; Communicable Diseases, Emerging; Humans; Japan; Macrolides; Mycobacterium ulcerans; Plasmids; Polyketide Synthases; Virulence Factors
PubMed: 23514902
DOI: 10.7883/yoken.66.83 -
Journal of Bacteriology Mar 2005A novel category of variable tandem repeats (VNTR) called mycobacterial interspersed repetitive units (MIRUs) has been identified for Mycobacterium ulcerans (n = 39), M....
A novel category of variable tandem repeats (VNTR) called mycobacterial interspersed repetitive units (MIRUs) has been identified for Mycobacterium ulcerans (n = 39), M. marinum (n = 27), and one related organism. Fifteen MIRU loci were identified in the genome of M. marinum and were used to genotype M. ulcerans, M. marinum, and an M. marinum-like organism that is considered a possible missing link between M. marinum and M. ulcerans. Seven MIRU loci were polymorphic, and locus-specific PCRs for four of these loci differentiated seven M. ulcerans genotypes, four M. marinum genotypes, and a unique genotype for the missing link organism. The seven M. ulcerans genotypes were related to six different geographic origins of isolates. All isolates from West and Central Africa, including old and recent isolates, belonged to the same genotype, emphasizing the great spatiotemporal homogeneity among African isolates. Unlike the M. ulcerans genotypes, the four M. marinum genotypes could not be clearly related to the geographic origins of the isolates. According to MIRU-VNTR typing, all M. ulcerans and M. marinum isolates of American origin were closely related, suggesting a common American ancestor for these two pathogenic species on the American continents. MIRU typing has significant potential value for discriminating between reoccurrence and reinfection for M. ulcerans disease.
Topics: Bacterial Typing Techniques; Base Sequence; Genotype; Interspersed Repetitive Sequences; Minisatellite Repeats; Molecular Sequence Data; Mycobacterium marinum; Mycobacterium ulcerans; Phylogeny; Polymorphism, Genetic; Sequence Alignment; Sequence Homology, Nucleic Acid; Species Specificity
PubMed: 15716434
DOI: 10.1128/JB.187.5.1639-1647.2005 -
PloS One 2022In recent years reported cases of Buruli ulcer, caused by Mycobacterium ulcerans, have increased substantially in Victoria, Australia, with the epidemic also expanding...
In recent years reported cases of Buruli ulcer, caused by Mycobacterium ulcerans, have increased substantially in Victoria, Australia, with the epidemic also expanding geographically. To develop an understanding of how M. ulcerans circulates in the environment and transmits to humans we analyzed environmental samples collected from 115 properties of recent Buruli ulcer cases and from 115 postcode-matched control properties, for the presence of M. ulcerans. Environmental factors associated with increased odds of M. ulcerans presence at a property included certain native plant species and native vegetation in general, more alkaline soil, lower altitude, the presence of common ringtail possums (Pseudocheirus peregrinus) and overhead powerlines. However, only overhead powerlines and the absence of the native plant Melaleuca lanceolata were associated with Buruli ulcer case properties. Samples positive for M. ulcerans were more likely to be found at case properties and were associated with detections of M. ulcerans in ringtail possum feces, supporting the hypothesis that M. ulcerans is zoonotic, with ringtail possums the strongest reservoir host candidate. However, the disparity in environmental risk factors associated with M. ulcerans positive properties versus case properties indicates the involvement of human behavior or the influence of other environmental factors in disease acquisition that requires further study.
Topics: Animals; Humans; Buruli Ulcer; Environmental Microbiology; Marsupialia; Mycobacterium ulcerans; Risk Factors; Victoria
PubMed: 36099259
DOI: 10.1371/journal.pone.0274627 -
PLoS Neglected Tropical Diseases Feb 2021Mycobacterium ulcerans is the causative agent of the chronic, necrotizing skin disease Buruli ulcer. Modes of transmission and molecular mechanisms involved in the...
Mycobacterium ulcerans is the causative agent of the chronic, necrotizing skin disease Buruli ulcer. Modes of transmission and molecular mechanisms involved in the establishment of M. ulcerans infections are poorly understood. Interactions with host glycans are often crucial in bacterial pathogenesis and the 22 kDa M. ulcerans protein MUL_3720 has a putative role in host cell attachment. It has a predicted N-terminal lectin domain and a C-terminal peptidoglycan-binding domain and is highly expressed on the surface of the bacilli. Here we report the glycan-binding repertoire of whole, fixed M. ulcerans bacteria and of purified, recombinant MUL_3720. On an array comprising 368 diverse biologically relevant glycan structures, M. ulcerans cells showed binding to 64 glycan structures, representing several distinct classes of glycans, including sulfated structures. MUL_3720 bound only to glycans containing sulfated galactose and GalNAc, such as glycans known to be associated with keratins isolated from human skin. Surface plasmon resonance studies demonstrated that both whole, fixed M. ulcerans cells and MUL_3720 show high affinity interactions with both glycans and human skin keratin extracts. This MUL_3720-mediated interaction with glycans associated with human skin keratin may contribute to the pathobiology of Buruli ulcer.
Topics: Buruli Ulcer; Epithelial Cells; Keratins; Membrane Proteins; Mycobacterium ulcerans; Polysaccharides; Skin; Sulfates
PubMed: 33630844
DOI: 10.1371/journal.pntd.0009136 -
Antimicrobial Agents and Chemotherapy Jan 2022For the treatment of chronic wounds, acid-oxidizing solutions (AOSs) with broad-spectrum microbicidal activity without disturbing granulation tissue formation have been...
For the treatment of chronic wounds, acid-oxidizing solutions (AOSs) with broad-spectrum microbicidal activity without disturbing granulation tissue formation have been developed. We found AOSs to efficiently kill Mycobacterium ulcerans, the causative agent of Buruli ulcer, which is able to survive harsh decontamination treatments. Topical AOS treatment of Buruli ulcer lesions may support the recommended antibiotic therapy (oral rifampin and clarithromycin), prevent contamination of the environment by the mycobacteria, and control secondary infections, which are a prevalent wound management problem in resource-poor settings where Buruli ulcer is endemic.
Topics: Buruli Ulcer; Clarithromycin; Humans; Mycobacterium ulcerans; Oxidation-Reduction; Rifampin
PubMed: 34662181
DOI: 10.1128/AAC.00870-21 -
Seminars in Immunopathology Jun 2020Mycobacterial pathogens can be categorized into three broad groups: Mycobacterium tuberculosis complex causing tuberculosis, M. leprae and M. lepromatosis causing... (Review)
Review
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.
Topics: Buruli Ulcer; Humans; Mycobacterium; Mycobacterium ulcerans; Skin
PubMed: 32100087
DOI: 10.1007/s00281-020-00790-4 -
Frontiers in Immunology 2022Buruli ulcer is a neglected tropical disease that is characterized by non-fatal lesion development. The causative agent is There are no known vectors or transmission...
Buruli ulcer is a neglected tropical disease that is characterized by non-fatal lesion development. The causative agent is There are no known vectors or transmission methods, preventing the development of control methods. There are effective diagnostic techniques and treatment routines; however, several socioeconomic factors may limit patients' abilities to receive these treatments. The Bacillus Calmette-Guérin vaccine developed against tuberculosis has shown limited efficacy, and no conventionally designed vaccines have passed clinical trials. This study aimed to generate a multi-epitope vaccine against from the major facilitator superfamily transporter protein using an immunoinformatics approach. Twelve genome assemblies were analyzed, resulting in the identification of 11 CD8 and 7 CD4 T-cell epitopes and 2 B-cell epitopes. These conserved epitopes were computationally predicted to be antigenic, immunogenic, non-allergenic, and non-toxic. The CD4 T-cell epitopes were capable of inducing interferon-gamma and interleukin-4. They successfully bound to their respective human leukocyte antigens alleles in docking studies. The expected global population coverage of the T-cell epitopes and their restricted human leukocyte antigens alleles was 99.90%. The population coverage of endemic regions ranged from 99.99% (Papua New Guinea) to 21.81% (Liberia). Two vaccine constructs were generated using the Toll-like receptors 2 and 4 agonists, LprG and RpfE, respectively. Both constructs were antigenic, non-allergenic, non-toxic, thermostable, basic, and hydrophilic. The DNA sequences of the vaccine constructs underwent optimization and were successfully cloned with the pET-28a(+) plasmid. The vaccine constructs were successfully docked to their respective toll-like receptors. Molecular dynamics simulations were carried out to analyze the binding interactions within the complex. The generated binding energies indicate the stability of both complexes. The constructs generated in this study display severable favorable properties, with construct one displaying a greater range of favorable properties. However, further analysis and laboratory validation are required.
Topics: Humans; Epitopes, B-Lymphocyte; Epitopes, T-Lymphocyte; HLA Antigens; Mycobacterium ulcerans; Neglected Diseases; Bacterial Vaccines; Buruli Ulcer
PubMed: 36426350
DOI: 10.3389/fimmu.2022.1023558 -
PLoS Neglected Tropical Diseases Dec 2023Chronic tropical cutaneous ulcers remain a neglected medical condition in West Africa, particularly Buruli ulcer, which is caused by mycolactone cytotoxin-secreting...
BACKGROUND
Chronic tropical cutaneous ulcers remain a neglected medical condition in West Africa, particularly Buruli ulcer, which is caused by mycolactone cytotoxin-secreting Mycobacterium ulcerans (M. ulcerans). Medical management of this highly debilitating and necrotising skin infection may be modified by colonisation and co-infection of the ulcer by opportunistic and pathogenic microorganisms, which considerably delays and increases the cost of treatment.
METHODOLOGY/PRINCIPAL FINDING
We diagnosed chronic tropical cutaneous ulcers in nine patients in Côte d'Ivoire using M. ulcerans-specific PCRs and culturomics. This revealed M. ulcerans in 7/9 ulcer swabs and 5/9 control swabs as well as an additional 122 bacterial species, 32 of which were specific to ulcers, 61 specifics to the controls, and 29 which were shared, adding 40 bacterial species to those previously reported. Whole genome sequencing of four Bordetella trematum (B. trematum) isolates in four Buruli ulcer swabs and no controls indicated cytolethal distending toxins, as confirmed by cytotoxic assay.
CONCLUSIONS/SIGNIFICANCE
In four cases of Buruli ulcer in Côte d'Ivoire, B. trematum was a co-pathogen which was resistant to rifampicin and clarithromycin, unmatching M. ulcerans antibiotic susceptibility profile and counteracting the current treatment of Buruli ulcer in West Africa and Australia. Thus, we report here chronic mixed M. ulcerans-B. trematum chronic tropical ulcer as a specific form of Buruli ulcer in West Africa.
Topics: Humans; Mycobacterium ulcerans; Buruli Ulcer; Ulcer; Cote d'Ivoire; Skin Ulcer; Communicable Diseases
PubMed: 38060465
DOI: 10.1371/journal.pntd.0011413