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Pathogens (Basel, Switzerland) Aug 2023Buruli ulcer (BU) is a bacterial skin infection that is caused by and mainly affects people who reside in the rural areas of Africa and in suburban and beach resort... (Review)
Review
Buruli ulcer (BU) is a bacterial skin infection that is caused by and mainly affects people who reside in the rural areas of Africa and in suburban and beach resort communities in Australia. The infection typically begins as a painless papule or nodule that gradually develops into a large ulcer that can cause substantial impairment, damaging soft tissues and even bones. Early detection and immediate treatment are crucial to preventing further tissue damage and any potential complications, although it is worth noting that access to proper therapeutic resources can be limited in certain areas. The most commonly used antibiotics for treating BU are rifampicin, streptomycin, and clarithromycin; efforts have recently been made to introduce new treatments that increase the effectiveness and adherence to therapy. This article presents the latest research and management strategies regarding BU, providing an updated and intriguing perspective on this topic.
PubMed: 37764896
DOI: 10.3390/pathogens12091088 -
Journal of Clinical Tuberculosis and... Feb 2024Wound measurements are relevant in monitoring the rate of healing (RoH) and may predict time to healing. Predicting the time to healing can help improve the management...
INTRODUCTION
Wound measurements are relevant in monitoring the rate of healing (RoH) and may predict time to healing. Predicting the time to healing can help improve the management of Buruli ulcer. We examine three methods for the determination of RoH and their use as predictors of time to healing.
METHODS
Lesion measurements of Buruli ulcer patients treated from 2007 to 2022 were obtained with acetate sheet tracings (2D) or Aranz software (3D) fortnightly. RoH was determined using the absolute area, percentage area reduction and linear methods at 4 weeks post onset of antibiotic treatment. Predicted time to healing was compared to the actual healing time. Baseline characteristics were assessed for associations with healing.
RESULTS
All three methods for calculating the RoH significantly distinguished between fast and slow healers (p < 0.0001). The predicted healing time using the linear method was comparable to the actual healing time for fast healers (p = 0.34). The RoH was influenced by the form of lesion, with plaques [OR 2.19 5 %CI (1.2-3.6), p = 0.009], and oedemas [OR 8.5; 95 %CI (1.9--36.9), p = 0.004] being associated with delayed healing. The proportion of patients with paradoxical reactions 16 % vs 3 %, p < 0.0001), higher baseline bacterial load (75/104;72 % vs 21/47;45 %, p = 0.001) and delayed clearance of viable organisms (71/104;68 % vs 9/47;19 %, p < 0.0001) was higher in the slow healers than the fast healers.
CONCLUSION
Predicted healing rates were comparatively lower for slow healers than fast healers. Baseline characteristics associated with healing can be explored for an improved disease management plan to reduce patient and caregiver anxiety.
PubMed: 38292054
DOI: 10.1016/j.jctube.2024.100415 -
Emerging Infectious Diseases Oct 2023To examine protective and risk factors for Buruli ulcer (BU), we conducted a case-control study of 245 adult BU cases and 481 postcode-matched controls across BU-endemic...
To examine protective and risk factors for Buruli ulcer (BU), we conducted a case-control study of 245 adult BU cases and 481 postcode-matched controls across BU-endemic areas of Victoria, Australia. We calculated age- and sex-adjusted odds ratios for socio-environmental, host, and behavioral factors associated with BU by using conditional logistic regression. Odds of BU were >2-fold for persons with diabetes mellitus and persons working outdoors who had soil contact in BU-endemic areas (compared with indoor work) but were lower among persons who had bacillus Calmette-Guérin vaccinations. BU was associated with increasing numbers of possums and with ponds and bore water use at residences. Using insect repellent, covering arms and legs outdoors, and immediately washing wounds were protective; undertaking multiple protective behaviors was associated with the lowest odds of BU. Skin hygiene/protection behaviors and previous bacillus Calmette-Guérin vaccination might provide protection against BU in BU-endemic areas.
Topics: Adult; Humans; BCG Vaccine; Buruli Ulcer; Case-Control Studies; Risk Factors; Victoria
PubMed: 37735741
DOI: 10.3201/eid2910.230011 -
Heliyon Nov 2023Buruli ulcer (BU), a neglected tropical disease (NTD), is an infection of the skin and subcutaneous tissue caused by . The disease has been documented in many South... (Review)
Review
Buruli ulcer (BU), a neglected tropical disease (NTD), is an infection of the skin and subcutaneous tissue caused by . The disease has been documented in many South American, Asian, and Western Pacific countries and is widespread throughout much of Africa, especially in West and Central Africa. In rural areas with scarce medical care, BU is a devastating disease that can leave patients permanently disabled and socially stigmatized. is thought to produce a mycolactone toxin, which results in necrosis of the afflicted tissue and may be involved in the etiology of BU. Initially, patients may notice a painless nodule or plaque on their skin; as the disease progresses, however, it may spread to other parts of the body, including the muscles and bones. Clinical signs, microbial culture, and histological analysis of afflicted tissue all contribute to a diagnosis of BU. Though antibiotic treatment and surgical removal of infected tissue are necessary for BU management, plant-derived medicine could be an alternative in areas with limited access to conventional medicine. Herein we reviewed the geographical distribution, socioeconomic, risk factors, diagnosis, biology and ecology of the pathogen. Complex environmental, socioeconomic, and genetic factors that influence BU are discussed. Further, our review highlights future research areas needed to develop strategies to manage the disease through the use of indigenous African plants.
PubMed: 38034712
DOI: 10.1016/j.heliyon.2023.e22018 -
Microbiology Spectrum Jun 2023Mycobacterium ulcerans, an environmental opportunistic pathogen, causes necrotic cutaneous and subcutaneous lesions, named Buruli ulcers, in tropical countries....
Mycobacterium ulcerans, an environmental opportunistic pathogen, causes necrotic cutaneous and subcutaneous lesions, named Buruli ulcers, in tropical countries. PCR-derived tests used to detect M. ulcerans in environmental and clinical samples do not allow one-shot detection, identification, and typing of M. ulcerans among closely related Mycobacterium marinum complex mycobacteria. We established a 385-member M. marinum/M. ulcerans complex whole-genome sequence database by assembling and annotating 341 M. marinum/M. ulcerans complex genomes and added 44 M. marinum/M. ulcerans complex whole-genome sequences already deposited in the NCBI database. Pangenome, core genome, and single-nucleotide polymorphism (SNP) distance-based comparisons sorted the 385 strains into 10 M. ulcerans taxa and 13 M. marinum taxa, correlating with the geographic origin of strains. Aligning conserved genes identified one (proline-proline-glutamate) gene sequence to be species and intraspecies specific, thereby genotyping the 23 M. marinum/M. ulcerans complex taxa. PCR sequencing of the gene correctly genotyped nine M. marinum/M. ulcerans complex isolates among one M. marinum taxon and three M. ulcerans taxa in the African taxon (T2.4). Further, successful gene PCR sequencing in 15/21 (71.4%) swabs collected from suspected Buruli ulcer lesions in Côte d'Ivoire exhibited positive M. ulcerans 2404 real-time PCR and identified the M. ulcerans T2.4.1 genotype in eight swabs and M. ulcerans T2.4.1/T2.4.2 mixed genotypes in seven swabs. gene sequencing could be used as a proxy for whole-genome sequencing for the one-shot detection, identification, and typing of clinical M. ulcerans strains, offering an unprecedented tool for identifying M. ulcerans mixed infections. We describe a new targeted sequencing approach that characterizes the gene to disclose the simultaneous presence of different variants of a single pathogenic microorganism. This approach has direct implications on the understanding of pathogen diversity and natural history and potential therapeutic implications when dealing with obligate and opportunistic pathogens, such as Mycobacterium ulcerans presented here as a prototype.
Topics: Humans; Buruli Ulcer; Mycobacterium ulcerans; Cote d'Ivoire; Real-Time Polymerase Chain Reaction; Personal Protective Equipment
PubMed: 37222600
DOI: 10.1128/spectrum.00342-23 -
ACS Infectious Diseases Feb 2024In the recent decade, scientific communities have toiled to tackle the emerging burden of drug-resistant tuberculosis (DR-TB) and rapidly growing opportunistic... (Review)
Review
In the recent decade, scientific communities have toiled to tackle the emerging burden of drug-resistant tuberculosis (DR-TB) and rapidly growing opportunistic nontuberculous mycobacteria (NTM). Among these, two neglected mycobacteria species of the Acinetobacter family, and , are the etiological agents of leprosy and Buruli ulcer infections, respectively, and fall under the broad umbrella of neglected tropical diseases (NTDs). Unfortunately, lackluster drug discovery efforts have been made against these pathogenic bacteria in the recent decade, resulting in the discovery of only a few countable hits and majorly repurposing anti-TB drug candidates such as telacebec (Q203), P218, and TB47 for current therapeutic interventions. Major ignorance in drug candidate identification might aggravate the dramatic consequences of rapidly spreading mycobacterial NTDs in the coming days. Therefore, this Review focuses on an up-to-date account of drug discovery efforts targeting selected druggable targets from both bacilli, including the accompanying challenges that have been identified and are responsible for the slow drug discovery. Furthermore, a succinct discussion of the all-new possibilities that could be alternative solutions to mitigate the neglected mycobacterial NTD burden and subsequently accelerate the drug discovery effort is also included. We anticipate that the state-of-the-art strategies discussed here may attract major attention from the scientific community to navigate and expand the roadmap for the discovery of next-generation therapeutics against these NTDs.
Topics: Humans; Mycobacterium ulcerans; Mycobacterium leprae; Buruli Ulcer; Mycobacterium
PubMed: 38295025
DOI: 10.1021/acsinfecdis.3c00371 -
PLoS Neglected Tropical Diseases Jan 2024Little attention has been paid to neglected tropical diseases (NTDs) in high-income countries and no literature provides an overview of NTDs in Japan. This scoping... (Review)
Review
Little attention has been paid to neglected tropical diseases (NTDs) in high-income countries and no literature provides an overview of NTDs in Japan. This scoping review aims to synthesize the latest evidence and information to understand epidemiology of and public health response to NTDs in Japan. Using three academic databases, we retrieved articles that mentioned NTDs in Japan, written in English or Japanese, and published between 2010 and 2020. Websites of key public health institutions and medical societies were also explored. From these sources of information, we extracted data that were relevant to answering our research questions. Our findings revealed the transmission of alveolar echinococcosis, Buruli ulcer, Chagas disease, dengue, foodborne trematodiases, mycetoma, scabies, and soil-transmitted helminthiasis as well as occurrence of snakebites within Japan. Other NTDs, such as chikungunya, cystic echinococcosis, cysticercosis, leishmaniasis, leprosy, lymphatic filariasis, rabies, and schistosomiasis, have been imported into the country. Government agencies tend to organize surveillance and control programs only for the NTDs targeted by the Infectious Disease Control Law, namely, echinococcosis, rabies, dengue, and chikungunya. At least one laboratory offers diagnostic testing for each NTD except for dracunculiasis, human African trypanosomiasis, onchocerciasis, and yaws. No medicine is approved for treatment of Chagas disease and fascioliasis and only off-label use drugs are available for cysticercosis, opisthorchiasis, human African trypanosomiasis, onchocerciasis, schistosomiasis, and yaws. Based on these findings, we developed disease-specific recommendations. In addition, three policy issues are discussed, such as lack of legal frameworks to organize responses to some NTDs, overreliance on researchers to procure some NTD products, and unaffordability of unapproved NTD medicines. Japan should recognize the presence of NTDs within the country and need to address them as a national effort. The implications of our findings extend beyond Japan, emphasizing the need to study, recognize, and address NTDs even in high-income countries.
Topics: Animals; Humans; Japan; Onchocerciasis; Trypanosomiasis, African; Neglected Diseases; Rabies; Chikungunya Fever; Yaws; Tropical Medicine; Schistosomiasis; Chagas Disease; Cysticercosis; Dengue
PubMed: 38166156
DOI: 10.1371/journal.pntd.0011854 -
Frontiers in Microbiology 2023causes Buruli Ulcer, a neglected infectious skin disease that typically progresses from an early non-ulcerative lesion to an ulcer with undermined edges. If not...
causes Buruli Ulcer, a neglected infectious skin disease that typically progresses from an early non-ulcerative lesion to an ulcer with undermined edges. If not promptly treated, these lesions can lead to severe disfigurement and disability. The standard antibiotic regimen for Buruli Ulcer treatment has been oral rifampicin combined with intramuscular streptomycin administered daily for 8 weeks. However, there has been a recent shift toward replacing streptomycin with oral clarithromycin. Despite the advantages of this antibiotic regimen, it is limited by low compliance, associated side effects, and refractory efficacy for severe ulcerative lesions. Therefore, new drug candidates with a safer pharmacological spectrum and easier mode of administration are needed. Statins are lipid-lowering drugs broadly used for dyslipidemia treatment but have also been reported to have several pleiotropic effects, including antimicrobial activity against fungi, parasites, and bacteria. In the present study, we tested the susceptibility of to several statins, namely atorvastatin, simvastatin, lovastatin and fluvastatin. Using broth microdilution assays and cultures of -infected macrophages, we found that atorvastatin, simvastatin and fluvastatin had antimicrobial activity against . Furthermore, when using the checkerboard assay, the combinatory additive effect of atorvastatin and fluvastatin with the standard antibiotics used for Buruli Ulcer treatment highlighted the potential of statins as adjuvant drugs. In conclusion, statins hold promise as potential treatment options for Buruli Ulcer. Further studies are necessary to validate their effectiveness and understand the mechanism of action of statins against .
PubMed: 37840746
DOI: 10.3389/fmicb.2023.1266261 -
Toxins May 2023"Recognizing a surprising fact is the first step towards discovery." This famous quote from Louis Pasteur is particularly appropriate to describe what led us to study... (Review)
Review
"Recognizing a surprising fact is the first step towards discovery." This famous quote from Louis Pasteur is particularly appropriate to describe what led us to study mycolactone, a lipid toxin produced by the human pathogen . is the causative agent of Buruli ulcer, a neglected tropical disease manifesting as chronic, necrotic skin lesions with a "surprising" lack of inflammation and pain. Decades after its first description, mycolactone has become much more than a mycobacterial toxin. This uniquely potent inhibitor of the mammalian translocon (Sec61) helped reveal the central importance of Sec61 activity for immune cell functions, the spread of viral particles and, unexpectedly, the viability of certain cancer cells. We report in this review the main discoveries that marked our research into mycolactone, and the medical perspectives they opened up. The story of mycolactone is not over and the applications of Sec61 inhibition may go well beyond immunomodulation, viral infections, and oncology.
Topics: Animals; Humans; Buruli Ulcer; Mycobacterium ulcerans; Macrolides; Bacterial Toxins; Mammals
PubMed: 37368670
DOI: 10.3390/toxins15060369