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Pharmaceuticals (Basel, Switzerland) May 2024There are more than 170 known species of non-tuberculous mycobacteria, and some are responsible for serious diseases in people infected with them. One of these is Buruli...
There are more than 170 known species of non-tuberculous mycobacteria, and some are responsible for serious diseases in people infected with them. One of these is Buruli ulcers, a neglected tropical disease endemic in more than 33 countries and caused by , which infects skin tissue. Treatment consists of a long-term regimen combining the use of oral rifampin with another anti-tuberculosis drug (e.g., clarithromycin). Patients in these countries face difficulties in accessing and adhering to this therapy. This study investigates the feasibility of formulating stable, optimized clarithromycin as a topical cutaneous cream. The cream was formulated, and its stability was evaluated under different storage temperature conditions and using a stability indicator method. The results showed that the clarithromycin cream was stable for at least 60 days, even at extreme temperatures (40 °C). In conclusion, the data presented here demonstrate the stability of a new form of topical cutaneous clarithromycin, which may offer a new approach to the treatment of Buruli ulcers and clarithromycin-sensitive infections.
PubMed: 38931358
DOI: 10.3390/ph17060691 -
International Journal of... Apr 2024Environmental mycobacteria are involved in several infections ranging from lung to skin infections. In Côte d'Ivoire, apart from Mycobacterium ulcerans and...
BACKGROUND
Environmental mycobacteria are involved in several infections ranging from lung to skin infections. In Côte d'Ivoire, apart from Mycobacterium ulcerans and Mycobacterium tuberculosis, little information exists on other species. The culture of these species, a real challenge, especially in developing countries like Cote d'Ivoire, limits their identification. However, there are reports in literature of infections caused by these mycobacteria, and few species have never been described in human or animal infections. These are difficult cases to treat because of their resistance to most antituberculosis antibiotics. The aim of our work was to study the diversity of potentially pathogenic mycobacterial species in wastewater drainage channels in different townships and in two hospital effluents in the city of Abidjan.
METHODS
Wastewater samples were cultured, followed by conventional polymerase chain reaction (PCR) targeting mycobacterial 16S ribonucleic acid (16S RNA) using PA/MSHA primers. 16 S RNA identified were sequenced by Sanger techniques. Sequences obtained were analyzed, and a phylogenic tree was built.
RESULTS
Fast-growing mycobacteria, including Mycobacterium fortuitum, Mycobacterium phocaicum, Mycobacterium sp., and others presence, were confirmed both by culture and molecular techniques. M. fortuitum strain was the same in effluents of the Treichville University Hospital and in the wastewater of the township of Koumassi. New species never isolated in Côte d'Ivoire, such as M. phocaicum, have been identified in wastewater of the township of Yopougon.
CONCLUSION
This study showed that the sewer network in the city of Abidjan is colonized by both potentially pathogenic mycobacteria and saprophytic environmental mycobacteria.
Topics: Cote d'Ivoire; Phylogeny; RNA, Ribosomal, 16S; Humans; Nontuberculous Mycobacteria; Wastewater; Polymerase Chain Reaction; DNA, Bacterial; Mycobacterium
PubMed: 38916386
DOI: 10.4103/ijmy.ijmy_96_24 -
Microbiology Spectrum Jun 2024A human challenge model has the potential to fundamentally advance our understanding of early human immune responses to infection, while rapidly evaluating vaccines and...
UNLABELLED
A human challenge model has the potential to fundamentally advance our understanding of early human immune responses to infection, while rapidly evaluating vaccines and other therapeutic interventions. Here, using a murine tail infection model, we tested a very well-characterized working cell bank of the proposed challenge isolate JKD8049 in naïve and bacille Calmette-Guérin (BCG)-vaccinated BALB/c mice. All 10 naïve mice were successfully infected with 20 colony-forming units (CFU) of [95% confidence interval (CI) 17-22 CFU] with a mean time to visible lesion of 86 days (95% CI 79-92 days). In the 10 vaccinated mice, there was a significant delay in the mean time to lesion compared to the naïve controls of 24 days ( = 0.0003), but all mice eventually developed ulcerative lesions. This study informs a future human infection model by demonstrating the successful application of the challenge agent in this model and highlights both the promise and the problems with trying to induce protective immunity against .
IMPORTANCE
In preparation for its proposed use in a controlled human infection model (CHIM), this study reports the successful infection of BALB/c mice using a carefully characterized, low-dose inoculum of JKD8049 (our proposed CHIM strain). We also demonstrate that bacille Calmette-Guérin delays the onset of disease but cannot alter the course of illness once a lesion becomes apparent. We also validate the findings of previous low-dose challenges that used less accurate methods to determine the inoculum, but our presented methodology is practical, accurate, and anticipated to be reproducible.
PubMed: 38916323
DOI: 10.1128/spectrum.00555-24 -
Journal of Visual Communication in... May 2024Buruli ulcer (BU) is a skin infection caused by and a neglected tropical disease of the skin (skin NTD). Antibiotic treatments are available but, to be effective in the...
Buruli ulcer (BU) is a skin infection caused by and a neglected tropical disease of the skin (skin NTD). Antibiotic treatments are available but, to be effective in the absence of surgery, BU must be detected at its earliest stages (an innocuous-looking lump under the skin) and adherence to prescribed drugs must be high. This study aimed to develop multisensory medical illustrations of BU to support communication with at-risk communities. We used a Think Aloud method to explore community health workers' (n = 6) experiences of BU with a focus on the role of their five senses, since these non-medical disease experts are familiar with the day-to-day challenges presented by BU. Thematic analysis of the transcripts identified three key themes relating to 'Detection,' 'Help Seeking,' and 'Adherence' with a transcending theme 'Senses as key facilitators of health care'. New medical illustrations, for which we coin the phrase "5D illustrations" (signifying the contribution of the five senses) were then developed to reflect these themes. The senses therefore facilitated an enriched narrative enabling the production of relevant and useful visuals for health communication. The medical artist community could utilise sensory experiences to create dynamic medical illustrations for use in practice.
PubMed: 38771591
DOI: 10.1080/17453054.2024.2348170 -
Travel Medicine and Infectious Disease May 2024no abstract requested for correspondance items.
no abstract requested for correspondance items.
PubMed: 38754530
DOI: 10.1016/j.tmaid.2024.102725 -
PLoS Neglected Tropical Diseases May 2024Critical scientific questions remain regarding infection with Mycobacterium ulcerans, the organism responsible for the neglected tropical disease, Buruli ulcer (BU). A...
Critical scientific questions remain regarding infection with Mycobacterium ulcerans, the organism responsible for the neglected tropical disease, Buruli ulcer (BU). A controlled human infection model has the potential to accelerate our knowledge of the immunological correlates of disease, to test prophylactic interventions and novel therapeutics. Here we present microbiological evidence supporting M. ulcerans JKD8049 as a suitable human challenge strain. This non-genetically modified Australian isolate is susceptible to clinically relevant antibiotics, can be cultured in animal-free and surfactant-free media, can be enumerated for precise dosing, and has stable viability following cryopreservation. Infectious challenge of humans with JKD8049 is anticipated to imitate natural infection, as M. ulcerans JKD8049 is genetically stable following in vitro passage and produces the key virulence factor, mycolactone. Also reported are considerations for the manufacture, storage, and administration of M. ulcerans JKD8049 for controlled human infection.
Topics: Mycobacterium ulcerans; Buruli Ulcer; Humans; Anti-Bacterial Agents; Australia
PubMed: 38701090
DOI: 10.1371/journal.pntd.0011979 -
Nature Microbiology Apr 2024
PubMed: 38622381
DOI: 10.1038/s41564-024-01693-y -
Journal of Travel Medicine Apr 2024
PubMed: 38591861
DOI: 10.1093/jtm/taae057 -
PLoS Neglected Tropical Diseases Apr 2024Buruli ulcer (BU) is a skin neglected tropical disease (NTD) caused by Mycobacterium ulcerans. WHO-recommended treatment requires 8-weeks of daily rifampicin (RIF) and...
BACKGROUND
Buruli ulcer (BU) is a skin neglected tropical disease (NTD) caused by Mycobacterium ulcerans. WHO-recommended treatment requires 8-weeks of daily rifampicin (RIF) and clarithromycin (CLA) with wound care. Treatment compliance may be challenging due to socioeconomic determinants. Previous minimum Inhibitory Concentration and checkerboard assays showed that amoxicillin/clavulanate (AMX/CLV) combined with RIF+CLA were synergistic against M. ulcerans. However, in vitro time kill assays (TKA) are a better approach to understand the antimicrobial activity of a drug over time. Colony forming units (CFU) enumeration is the in vitro reference method to measure bacterial load, although this is a time-consuming method due to the slow growth of M. ulcerans. The aim of this study was to assess the in vitro activity of RIF, CLA and AMX/CLV combinations against M. ulcerans clinical isolates by TKA, while comparing four methodologies: CFU enumeration, luminescence by relative light unit (RLU) and optical density (at 600 nm) measurements, and 16S rRNA/IS2404 genes quantification.
METHODOLOGY/PRINCIPAL FINDINGS
TKA of RIF, CLA and AMX/CLV alone and in combination were performed against different M. ulcerans clinical isolates. Bacterial loads were quantified with different methodologies after 1, 3, 7, 10, 14, 21 and 28 days of treatment. RIF+AMX/CLV and the triple RIF+CLA+AMX/CLV combinations were bactericidal and more effective in vitro than the currently used RIF+CLA combination to treat BU. All methodologies except IS2404 quantitative PCR provided similar results with a good correlation with CFU enumeration. Measuring luminescence (RLU) was the most cost-effective methodology to quantify M. ulcerans bacterial loads in in vitro TKA.
CONCLUSIONS/SIGNIFICANCE
Our study suggests that alternative and faster TKA methodologies can be used in BU research instead of the cumbersome CFU quantification method. These results provide an in vitro microbiological support to of the BLMs4BU clinical trial (NCT05169554, PACTR202209521256638) to shorten BU treatment.
Topics: Humans; Clarithromycin; Rifampin; Mycobacterium ulcerans; RNA, Ribosomal, 16S; Anti-Bacterial Agents; Buruli Ulcer; Amoxicillin-Potassium Clavulanate Combination
PubMed: 38573915
DOI: 10.1371/journal.pntd.0011867 -
Microbiology Spectrum Apr 2024The classical lineage of is the most prevalent clonal group associated with Buruli ulcer in humans. Its reservoir is strongly associated with the environment. We...
UNLABELLED
The classical lineage of is the most prevalent clonal group associated with Buruli ulcer in humans. Its reservoir is strongly associated with the environment. We analyzed together 1,045 isolates collected from 13 countries on two continents to define the evolutionary history and population dynamics of this lineage. We confirm that this lineage spread over 7,000 years from Australia to Africa with the emergence of outbreaks in distinct waves in the 18th and 19th centuries. In sharp contrast with its global spread over the last century, transmission chains are now mostly local, with little or no dissemination between endemic areas. This study provides new insights into the phylogeography and population dynamics of highlighting the importance of comparative genomic analyses to improve our understanding of pathogen transmission.
IMPORTANCE
is an environmental mycobacterial pathogen that can cause Buruli ulcer, a severe cutaneous infection, mostly spread in Africa and Australia. We conducted a large genomic study of , combining genomic and evolutionary approaches to decipher its evolutionary history and pattern of spread at different geographic scales. At the scale of villages in an endemic area of Benin, the circulating genotypes have been introduced in recent decades and are not randomly distributed along the river. On a global scale, has been spreading for much longer, resulting in distinct and compartmentalized endemic foci across Africa and Australia.
Topics: Humans; Mycobacterium ulcerans; Buruli Ulcer; Phylogeny; Genomics; Biological Evolution
PubMed: 38441471
DOI: 10.1128/spectrum.03827-23