-
International Journal of... Jun 2015Mycobacterium ulcerans (MU) produces mycolactone toxin when infected with a plasmid. Toxin is cytotoxic and immunosuppressive, causing extensive destruction of tissues,...
BACKGROUND
Mycobacterium ulcerans (MU) produces mycolactone toxin when infected with a plasmid. Toxin is cytotoxic and immunosuppressive, causing extensive destruction of tissues, leading to large ulcers on exposed parts of the body. Spontaneous healing by secondary intention leads to contractures, subluxation of joints, disuse atrophy, distal lymphedema and other complications. The disease is endemic in some communities within the middle belt of Ghana.
OBJECTIVE
To document the clinical and epidemiological features of MU disease in the middle belt of Ghana and the outcome of treatment.
PATIENTS AND METHODS
Patients with lesions suspected to MU disease were screened by community workers. Lesions were confirmed by any of the following: direct smear examination, culture, polymerase chain reaction (PCR), or histopathology. Patients were treated with rifampicin (10mg/kg orally) and streptomycin (15 mg/kg IM) combination for eight weeks. Patients selected for surgical treatment included cases where medical treatment had failed, cases where medical treatment is contraindicated, cases presenting late with complications and recurrent cases.
RESULTS
258 patients were seen in the Ahafo Ano, Amansie Central, Amansie West, Asunafo, Asutifi, and Upper Denkyira districts of Ghana between 2005 and 2012. Their ages ranged from 1 year 3 months to 98 years, with a mean age of 29.8 (SD 20.4). The clinical forms of MU disease seen were: papule (0.5%), nodule (1.5%), chronic osteomyelitis (1.5%), contracture (1.5%), edematous lesion (3%), and ulcer (92%). Uncommon complications include subluxation of knee joint, salivary gland fistula and Marjolin's ulcer. The lesions were distributed as follows: head and neck (6.8%), upper limb (20.3%), trunk (1.7%), and lower limb (71.2%).
CONCLUSION
MU disease in the middle belt of Ghana can be controlled by early case detection and adequate curative treatment.
Topics: Adolescent; Adult; Anti-Bacterial Agents; Buruli Ulcer; Child; Endemic Diseases; Female; Ghana; Humans; Male; Mycobacterium ulcerans; Rifampin; Streptomycin; Young Adult
PubMed: 26972882
DOI: 10.1016/j.ijmyco.2015.03.006 -
Emerging Infectious Diseases Mar 2020Mycobacterium ulcerans is the causative agent of Buruli ulcer, a neglected tropical disease found in rural areas of West and Central Africa. Despite the ongoing efforts...
Mycobacterium ulcerans is the causative agent of Buruli ulcer, a neglected tropical disease found in rural areas of West and Central Africa. Despite the ongoing efforts to tackle Buruli ulcer epidemics, the environmental reservoir of its pathogen remains elusive, underscoring the need for new approaches to improving disease prevention and management. In our study, we implemented a local-scale spatial clustering model and deciphered the genetic diversity of the bacteria in a small area of Benin where Buruli ulcer is endemic. Using 179 strain samples from West Africa, we conducted a phylogeographic analysis combining whole-genome sequencing with spatial scan statistics. The 8 distinct genotypes we identified were by no means randomly spread over the studied area. Instead, they were divided into 3 different geographic clusters, associated with landscape characteristics. Our results highlight the ability of M. ulcerans to evolve independently and differentially depending on location in a specific ecologic reservoir.
Topics: Benin; Buruli Ulcer; DNA, Bacterial; Disease Reservoirs; Genotype; Humans; Mycobacterium ulcerans; Phylogeography; Water Microbiology
PubMed: 32091371
DOI: 10.3201/eid2603.190573 -
Open Biology Nov 2023Buruli ulcer (BU) is a neglected tropical disease. It is caused by the bacterium and is characterized by skin lesions. Several studies were performed testing the...
Buruli ulcer (BU) is a neglected tropical disease. It is caused by the bacterium and is characterized by skin lesions. Several studies were performed testing the Bacillus Calmette-Guérin (BCG) vaccine in human and animal models and specific vaccines in animal models. However, there are currently no clinically accepted vaccines to prevent infection. The aim of this study was to identify T-cell and B-cell epitopes from the mycobacterial membrane protein large (MmpL) proteins of These epitopes were analysed for properties including antigenicity, immunogenicity, non-allergenicity, non-toxicity, population coverage and the potential to induce cytokines. The final 8 CD8, 12 CD4 T-cell and 5 B-cell epitopes were antigenic, non-allergenic and non-toxic. The estimated global population coverage of the CD8 and CD4 epitopes was 97.71%. These epitopes were used to construct five multi-epitope vaccine constructs with different adjuvants and linker combinations. The constructs underwent further structural analyses and refinement. The constructs were then docked with Toll-like receptors. Three of the successfully docked complexes were structurally analysed. Two of the docked complexes successfully underwent molecular dynamics simulations (MDS) and post-MDS analysis. The complexes generated were found to be stable. However, experimental validation of the complexes is required.
Topics: Humans; Animals; Mycobacterium ulcerans; Membrane Proteins; Epitopes, B-Lymphocyte; Buruli Ulcer; Vaccines; Epitopes, T-Lymphocyte; Molecular Docking Simulation
PubMed: 37935359
DOI: 10.1098/rsob.230330 -
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 -
Methods in Molecular Biology (Clifton,... 2022Generation and characterization of drug resistant mutants is a powerful tool in antimicrobial drug discovery for identification of the molecular target of an...
Generation and characterization of drug resistant mutants is a powerful tool in antimicrobial drug discovery for identification of the molecular target of an investigational drug candidate. The method is relatively simple to be conducted in a classical microbiology laboratory. Its value has been augmented by the employment of next generation sequencing techniques to characterize single-nucleotide polymorphisms associated with drug resistance. Determination of the frequency of emergence of resistance to drug candidates also provides insights into their usefulness for clinical application. In addition to the generation of drug resistant mutants, we describe a direct method to determine the minimum inhibitory concentration of a drug candidate against Mycobacterium ulcerans.
Topics: Anti-Bacterial Agents; Buruli Ulcer; Humans; Microbial Sensitivity Tests; Mycobacterium ulcerans; Pharmaceutical Preparations
PubMed: 34643915
DOI: 10.1007/978-1-0716-1779-3_20 -
BMC Infectious Diseases Mar 2019Buruli ulcer (BU) is a chronic, necrotizing infectious skin disease caused by Mycobacterium ulcerans. In recent years, there has been a decrease in the number of new...
BACKGROUND
Buruli ulcer (BU) is a chronic, necrotizing infectious skin disease caused by Mycobacterium ulcerans. In recent years, there has been a decrease in the number of new cases detected. This study aimed to show the evolution of its distribution in the Lalo District in Bénin from 2006 to 2017.
METHODS
The database of the BU Detection and Treatment Center of Lalo allowed us to identify 1017 new cases in the Lalo District from 2006 to 2017. The annual prevalence was calculated with subdistricts and villages. The trends of the demographic variables and those related to the clinical and treatment features were analysed using Microsoft Excel® 2007 and Epi Info® 7. Arc View version® 3.4 was used for mapping.
RESULTS
From 2006 to 2017, the case prevalence of BU in the Lalo District decreased by 95%. The spatial distribution of BU cases confirmed the foci of the distribution, as described in the literature. The most endemic subdistricts were Ahomadégbé, Adoukandji, Gnizounmè and Tchito, with a cumulative prevalence of 315, 225, 215 and 213 cases per 10,000 inhabitants, respectively. The least endemic subdistricts were Zalli, Banigbé, Lalo-Centre and Lokogba, with 16, 16, 10, and 5 cases per 10,000 inhabitants, respectively. A significant decrease in the number of patients with ulcerative lesions (p = 0.002), as well as those with category 3 lesions (p < 0.001) and those treated surgically (p < 0.001), was observed. The patients confirmed by PCR increased (from 40.42% in 2006 to 84.62% in 2017), and joint limitation decreased (from 13.41% in 2006 to 0.0% in 2017).
CONCLUSION
This study confirmed the general decrease in BU prevalence rates in Lalo District at the subdistrict and village levels, as also observed at the country level. This decrease is a result of the success of the BU control strategies implemented in Bénin, especially in the Lalo District.
Topics: Adult; Benin; Buruli Ulcer; Female; Humans; Male; Middle Aged; Mycobacterium ulcerans; Polymerase Chain Reaction; Prevalence
PubMed: 30871489
DOI: 10.1186/s12879-019-3845-2 -
Australian Veterinary Journal Jul 2013An ulcerative dermopathy caused by Mycobacterium ulcerans is described in two alpacas (Vicugna pacos) domiciled in endemic areas of Victoria, Australia.
BACKGROUND
An ulcerative dermopathy caused by Mycobacterium ulcerans is described in two alpacas (Vicugna pacos) domiciled in endemic areas of Victoria, Australia.
RESULTS
The diagnosis was confirmed in both cases by PCR targeting the M. ulcerans-specific insertion sequence, IS2404. Extensive wound debridement and bandaging was effective in controlling local disease in one alpaca, although the animal was eventually euthanased because of suspected disease recurrence at other anatomical sites. Treatment was not undertaken in the second animal, but the results of a complete necropsy are described. Investigation of the environs of the second animal yielded low levels of M. ulcerans DNA associated with a variety of samples. The potential use of adjunctive antibiotic therapies directed against M. ulcerans infection in this species is discussed.
CONCLUSION
Mycobacterium ulcerans infection should be suspected in alpacas domiciled in endemic areas and presented with ulcerative skin disease.
Topics: Animals; Buruli Ulcer; Camelids, New World; DNA Transposable Elements; DNA, Bacterial; Fatal Outcome; Female; Histocytochemistry; Mycobacterium ulcerans; Polymerase Chain Reaction; Skin Ulcer; Victoria
PubMed: 23782024
DOI: 10.1111/avj.12071 -
BMC Microbiology Jan 2017Mycobacterium ulcerans (M. ulcerans) is the causative agent of Buruli Ulcer (BU) disease. In order to inhibit the growth of the microbial contaminants during culture of...
BACKGROUND
Mycobacterium ulcerans (M. ulcerans) is the causative agent of Buruli Ulcer (BU) disease. In order to inhibit the growth of the microbial contaminants during culture of M. ulcerans, it is necessary to decontaminate BU samples with effective chemical agents. This study aimed at investigating some selected chemicals as potential decontamination agents for the isolation of M. ulcerans from swabs.
RESULTS
Povidone iodine at 0.5 and 1% exhibited the lowest contamination and recovery rate for microbial contaminants and M. ulcerans. The most effective decontamination method was the protocol using 2% cetylpyridinium chloride/4% sodium chloride (recovery rate = 53%, contamination rate = 14%). The observed difference between the recovery rate of 2% CPC/4% NaC and the other protocols was however not statistically significant (p = 0.76).
CONCLUSIONS
Two percent (2%) cetylpyridinium chloride/4% sodium chloride can be conveniently used as an alternative decontamination method for the isolation of M. ulcerans from swabs.
Topics: Anti-Infective Agents; Bacteriological Techniques; Buruli Ulcer; Cetylpyridinium; Decontamination; Ghana; Humans; Microbial Sensitivity Tests; Mycobacterium ulcerans; Oxalic Acid; Povidone-Iodine; Sodium Chloride
PubMed: 28056807
DOI: 10.1186/s12866-016-0918-x -
ELife Jul 2015Host-parasite interactions are often embedded within complex host communities and can be influenced by a variety of environmental factors, such as seasonal variations in...
Host-parasite interactions are often embedded within complex host communities and can be influenced by a variety of environmental factors, such as seasonal variations in climate or abiotic conditions in water and soil, which confounds our understanding of the main drivers of many multi-host pathogens. Here, we take advantage of a combination of large environmental data sets on Mycobacterium ulcerans (MU), an environmentally persistent microorganism associated to freshwater ecosystems and present in a large variety of aquatic hosts, to characterize abiotic and biotic factors driving the dynamics of this pathogen in two regions of Cameroon. We find that MU dynamics are largely driven by seasonal climatic factors and certain physico-chemical conditions in stagnant and slow-flowing ecosystems, with an important role of pH as limiting factor. Furthermore, water conditions can modify the effect of abundance and diversity of aquatic organisms on MU dynamics, which suggests a different contribution of two MU transmission routes for aquatic hosts (trophic vs environmental transmission) depending on local abiotic factors.
Topics: Cameroon; Chemical Phenomena; Climate; Ecosystem; Hydrogen-Ion Concentration; Mycobacterium ulcerans; Seasons; Water Microbiology
PubMed: 26216042
DOI: 10.7554/eLife.07616 -
PloS One 2023Mycolactone is a cytotoxic lipid metabolite produced by Mycobacterium ulcerans, the environmental pathogen responsible for Buruli ulcer, a neglected tropical disease....
Mycolactone is a cytotoxic lipid metabolite produced by Mycobacterium ulcerans, the environmental pathogen responsible for Buruli ulcer, a neglected tropical disease. Mycobacterium ulcerans is prevalent in West Africa, particularly found in lentic environments, where mosquitoes also occur. Researchers hypothesize mosquitoes could serve as a transmission mechanism resulting in infection by M. ulcerans when mosquitoes pierce skin contaminated with M. ulcerans. The interplay between the pathogen, mycolactone, and mosquito is only just beginning to be explored. A triple-choice assay was conducted to determine the host-seeking preference of Aedes aegypti between M. ulcerans wildtype (MU, mycolactone active) and mutant (MUlac-, mycolactone inactive). Both qualitative and quantitative differences in volatile organic compounds' (VOCs) profiles of MU and MUlac- were determined by GC-MS. Additionally, we evaluated the interplay between Ae. aegypti proximity and M. ulcerans mRNA expression. The results showed that mosquito attraction was significantly greater (126.0%) to an artificial host treated with MU than MUlac-. We found that MU and MUlac produced differential profiles of VOCs associated with a wide range of biological importance from quorum sensing (QS) to human odor components. RT-qPCR assays showed that mycolactone upregulation was 24-fold greater for MU exposed to Ae. aegypti in direct proximity. Transcriptome data indicated significant induction of ten chromosomal genes of MU involved in stress responses and membrane protein, compared to MUlac- when directly having access to or in near mosquito proximity. Our study provides evidence of possible interkingdom interactions between unicellular and multicellular species that MU present on human skin is capable of interreacting with unrelated species (i.e., mosquitoes), altering its gene expression when mosquitoes are in direct contact or proximity, potentially impacting the production of its VOCs, and consequently leading to the stronger attraction of mosquitoes toward human hosts. This study elucidates interkingdom interactions between viable M. ulcerans bacteria and Ae. aegypti mosquitoes, which rarely have been explored in the past. Our finding opens new doors for future research in terms of disease ecology, prevalence, and pathogen dispersal outside of the M. ulcerans system.
Topics: Animals; Humans; Mycobacterium ulcerans; Buruli Ulcer; Macrolides; Aedes; Gene Expression
PubMed: 37535670
DOI: 10.1371/journal.pone.0289768