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Tuberculosis (Edinburgh, Scotland) Sep 2023The Many Hosts of Mycobacteria (MHM) meeting series brings together basic scientists, clinicians and veterinarians to promote robust discussion and dissemination of... (Review)
Review
The Many Hosts of Mycobacteria (MHM) meeting series brings together basic scientists, clinicians and veterinarians to promote robust discussion and dissemination of recent advances in our knowledge of numerous mycobacterial diseases, including human and bovine tuberculosis (TB), nontuberculous mycobacteria (NTM) infection, Hansen's disease (leprosy), Buruli ulcer and Johne's disease. The 9th MHM conference (MHM9) was held in July 2022 at The Ohio State University (OSU) and centered around the theme of "Confounders of Mycobacterial Disease." Confounders can and often do drive the transmission of mycobacterial diseases, as well as impact surveillance and treatment outcomes. Various confounders were presented and discussed at MHM9 including those that originate from the host (comorbidities and coinfections) as well as those arising from the environment (e.g., zoonotic exposures), economic inequality (e.g. healthcare disparities), stigma (a confounder of leprosy and TB for millennia), and historical neglect (a confounder in Native American Nations). This conference report summarizes select talks given at MHM9 highlighting recent research advances, as well as talks regarding the historic and ongoing impact of TB and other infectious diseases on Native American Nations, including those in Southwestern Alaska where the regional TB incidence rate is among the highest in the Western hemisphere.
Topics: Animals; Cattle; Humans; Nontuberculous Mycobacteria; Mycobacterium tuberculosis; Mycobacterium Infections, Nontuberculous; Tuberculosis, Bovine; Coinfection
PubMed: 37531864
DOI: 10.1016/j.tube.2023.102377 -
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 -
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 -
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 -
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 -
The Journal of Infectious Diseases Nov 2023Mycobacterium ulcerans causes Buruli ulcer, the third most frequent mycobacterial disease after tuberculosis and leprosy. Transient clinical deteriorations, known as...
Mycobacterium ulcerans causes Buruli ulcer, the third most frequent mycobacterial disease after tuberculosis and leprosy. Transient clinical deteriorations, known as paradoxical reactions (PRs), occur in some patients during or after antibiotic treatment. We investigated the clinical and biological features of PRs in a prospective cohort of 41 patients with Buruli ulcer from Benin. Neutrophil counts decreased from baseline to day 90, and interleukin 6 (IL-6), granulocyte colony-stimulating factor, and vascular endothelial growth factor were the cytokines displaying a significant monthly decrease relative to baseline. PRs occurred in 10 (24%) patients. The baseline biological and clinical characteristics of the patients presenting with PRs did not differ significantly from those of the other patients. However, the patients with PRs had significantly higher IL-6 and tumor necrosis factor alpha (TNF-α) concentrations on days 30, 60, and 90 after the start of antibiotic treatment. The absence of a decrease in IL-6 and TNF-α levels during treatment should alert clinicians to the possibility of PR onset.
Topics: Humans; Buruli Ulcer; Prospective Studies; Tumor Necrosis Factor-alpha; Interleukin-6; Vascular Endothelial Growth Factor A; Anti-Bacterial Agents
PubMed: 37221015
DOI: 10.1093/infdis/jiad176 -
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 -
International Journal of Molecular... Sep 2023The identification of an emerging pathogen in humans can remain difficult by conventional methods such as enrichment culture assays that remain highly selective, require... (Review)
Review
The identification of an emerging pathogen in humans can remain difficult by conventional methods such as enrichment culture assays that remain highly selective, require appropriate medium and cannot avoid misidentifications, or serological tests that use surrogate antigens and are often hampered by the level of detectable antibodies. Although not originally designed for this purpose, the implementation of polymerase-chain-reaction (PCR) has resulted in an increasing number of diagnostic tests for many diseases. However, the design of specific molecular assays relies on the availability and reliability of published genetic sequences for the target pathogens as well as enough knowledge on the genetic diversity of species and/or variants giving rise to the same disease symptoms. Usually designed for clinical isolates, molecular tests are often not suitable for environmental samples in which the target DNA is mixed with a mixture of environmental DNA. A key challenge of such molecular assays is thus to ensure high specificity of the target genetic markers when focusing on clinical and environmental samples in order to follow the dynamics of disease transmission and emergence in humans. Here we focus on the Buruli ulcer (BU), a human necrotizing skin disease mainly affecting tropical and subtropical areas, commonly admitted to be caused by worldwide although other mycolactone-producing mycobacteria and even mycobacterium species were found associated with BU or BU-like cases. By revisiting the literature, we show that many studies have used non-specific molecular markers (IS, IS, KR-B) to identify from clinical and environmental samples and propose that all mycolactone-producing mycobacteria should be definitively considered as variants from the same group rather than different species. Importantly, we provide evidence that the diversity of mycolactone-producing mycobacteria variants as well as mycobacterium species potentially involved in BU or BU-like skin ulcerations might have been underestimated. We also suggest that the specific variants/species involved in each BU or BU-like case should be carefully identified during the diagnosis phase, either via the key to genetic identification proposed here or by broader metabarcoding approaches, in order to guide the medical community in the choice for the most appropriate antibiotic therapy.
PubMed: 37762030
DOI: 10.3390/ijms241813727