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PLoS Neglected Tropical Diseases Feb 2020Skin neglected tropical diseases (NTDs) such as Buruli ulcer (BU) and leprosy produce significant stigma and disability. Shared clinical presentations and needs for care...
BACKGROUND
Skin neglected tropical diseases (NTDs) such as Buruli ulcer (BU) and leprosy produce significant stigma and disability. Shared clinical presentations and needs for care present opportunities for integrated case management in co-endemic areas. As global policies are translated into local integrated services, there remains a need to monitor what new configurations of care emerge and how individuals experience them.
METHODS
To explore patient experiences of integrated case management for skin NTDs, in 2018, we conducted a field-based qualitative case series in a leprosy rehabilitation centre in Ganta, Liberia where BU services were recently introduced. Twenty patients with BU (n = 10) and leprosy (n = 10) participated in in-depth interviews that incorporated photography methods. We contextualised our findings with field observations and unstructured interviews with health workers.
FINDINGS
The integration of care for BU and leprosy prompted new conceptualisations of these diseases and experiences of NTD stigma. Some patients felt anxiety about using services because they feared being infected with the other disease. Other patients viewed the two diseases as 'intertwined': related manifestations of the same condition. Configurations of inter-disease stigma due to fear of transmission were buffered by joint health education sessions which also appeared to facilitate social support between patients in the facility. For both diseases, medication and wound care were viewed as the cornerstones of care and appreciated as interventions that led to rehabilitation of the whole patient group through shared experiences of healing, avoidance of physical deformities and stigma reduction. Patient accounts of intense pain during wound care for BU and inability of staff to manage severe complications, however, exposed some shortcomings of medical care for the newly integrated service, as did patient fears of long-lasting disability due to lack of physiotherapy services.
SIGNIFICANCE
Under integrated care policies, the possibility of new discourses about skin NTD identities emerging along with new configurations of stigma may have unanticipated consequences for patients' experiences of case management. The social experience of integrated medication and wound dressing has the potential to link patients within a single, supportive patient community. Control programmes with resource constraints should anticipate potential challenges of integrating care, including the need to ameliorate lasting disability and provide adequate clinical management of severe BU cases.
Topics: Buruli Ulcer; Case Management; Humans; Leprosy; Liberia; Neglected Diseases; Social Stigma; Social Support; Tropical Climate; Tropical Medicine
PubMed: 32023242
DOI: 10.1371/journal.pntd.0008030 -
Tropical Diseases, Travel Medicine and... Nov 2022Buruli ulcer (BU) is a debilitating neglected tropical disease which causes disability and mostly affects inhabitants in impoverished settings where access to medical...
BACKGROUND
Buruli ulcer (BU) is a debilitating neglected tropical disease which causes disability and mostly affects inhabitants in impoverished settings where access to medical care is challenging. This study aims to determine the effect of training community members as volunteers for or in the detection and referral of people who have Buruli ulcer to the hospital.
METHODS
The following study is a before and after study in the BU-endemic Local Government Areas (LGA) of Ebonyi State. A cluster random sampling technique was used to select 90 volunteers from three LGAs (30 from each LGA). In each LGA, the volunteers underwent a one-day training and six months field work to identify all those who have any form of ulcer on any part of their bodies. A short questionnaire was used to capture socio-demographic characteristics of the patient, site of the ulcer, duration of the ulcer, initial appearance of the ulcer, referral to hospital, result of laboratory investigation, and treatment received. The data was analysed using the Statistical Package for Social Sciences (SPSS) for Microsoft Windows version 20 software. The Z test statistic was used to compare the number of referred BU patients before and after the intervention by LGA. The Chi square test was used to examine the association between the dependent and independent variables.
RESULTS
The mean age of volunteers was 39 ± 9.5 while mean age of the patients was 42.3 ± 17.1. Most of the ulcers were on the legs (79.4%) and lasted 1-5 years (65.6%). There was a significant increase in the proportion of BU suspects identified by the community volunteers in all 3 LGAs (Afikpo north (p = < 0.001), Abakaliki (p = 0.02), Ikwo (p = 0.001). The duration of the ulcer was associated with the detection and referral of the patients with higher levels of detection and referral among those whose ulcer had lasted 1-5 years in two of the LGAs (P < 0.001).
CONCLUSION
We recommend that program managers and stakeholders integrate and scale up the services of trained community health volunteers for the rapid detection of Buruli ulcer cases in rural endemic communities. Awareness and sensitization campaigns on BU preventive measures should be intensified.
PubMed: 36316742
DOI: 10.1186/s40794-022-00181-7 -
Perceived water-related risk factors of Buruli ulcer in two villages of south-central Côte d'Ivoire.PLoS Neglected Tropical Diseases Dec 2022Buruli ulcer, caused by Mycobacterium ulcerans, is a neglected tropical skin disease that is primarily endemic in West and Central Africa, including Côte d'Ivoire....
BACKGROUND
Buruli ulcer, caused by Mycobacterium ulcerans, is a neglected tropical skin disease that is primarily endemic in West and Central Africa, including Côte d'Ivoire. Studies indicate that M. ulcerans infections are caused by contact with an environmental reservoir of the bacteria, governed by specific human biological conditions. Yet, the nature of this reservoir and the exact mode of transmission remain unknown.
METHODOLOGY
To identify ecologic risk factors of Buruli ulcer in south-central Côte d'Ivoire, we pursued a qualitative study matched with geo-referencing inquiry. Embedded in a broader integrated wound management research project, we (i) mapped households and water sources of laboratory confirmed Buruli ulcer cases and (ii) interviewed 12 patients and four health care workers to assess exposure to surface water and to deepen the understanding of perceived transmission pathways.
PRINCIPAL FINDINGS
Water availability, accessibility, and affordability were reported as key determinants for choosing water resources. Furthermore, perceived risks were related to environmental, structural, and individual factors. Despite the presence of improved water sources (e.g., drilled wells), communities heavily relied on unprotected surface water for a multitude of activities. The nearby Bandama River and seasonal waterbodies were frequently used for washing, bathing, and collection of water for drinking and cooking. Many residents also reported to cross the river on a daily basis for agricultural chores, and hence, are exposed to stagnant water during farming activities.
CONCLUSIONS/SIGNIFICANCE
Our study in two Buruli ulcer endemic villages in south-central Côte d'Ivoire revealed a wide range of water-related domestic activities that might expose people to an increased risk of contracting the disease. Environmental, biological, social, and cultural risk factors are closely interlinked and should be considered in future investigations of Buruli ulcer transmission. Active participation of the communities is key to better understand their circumstances to advance research and fight against Buruli ulcer and other neglected tropical diseases.
Topics: Humans; Buruli Ulcer; Water; Cote d'Ivoire; Mycobacterium ulcerans; Neglected Diseases; Risk Factors
PubMed: 36516125
DOI: 10.1371/journal.pntd.0010927 -
Antimicrobial Agents and Chemotherapy Jul 2019Buruli ulcer is treatable with antibiotics. An 8-week course of rifampin (RIF) and either streptomycin (STR) or clarithromycin (CLR) cures over 90% of patients. However,...
Buruli ulcer is treatable with antibiotics. An 8-week course of rifampin (RIF) and either streptomycin (STR) or clarithromycin (CLR) cures over 90% of patients. However, STR requires injections and may be toxic, and CLR shares an adverse drug-drug interaction with RIF and may be poorly tolerated. Studies in a mouse footpad infection model showed that increasing the dose of RIF or using the long-acting rifamycin rifapentine (RPT), in combination with clofazimine (CFZ), a relatively well-tolerated antibiotic, can shorten treatment to 4 weeks. CFZ is reduced by a component of the electron transport chain (ETC) to produce reactive oxygen species toxic to bacteria. Synergistic activity of CFZ with other ETC-targeting drugs, the ATP synthase inhibitor bedaquiline (BDQ) and the : oxidase inhibitor Q203 (now named telacebec), was recently described against Recognizing that mutants lacking the alternative oxidase are hypersusceptible to Q203 and that is a natural oxidase-deficient mutant, we tested the susceptibility of to Q203 and evaluated the treatment-shortening potential of novel 3- and 4-drug regimens combining RPT, CFZ, Q203, and/or BDQ in a mouse footpad model. The MIC of Q203 was extremely low (0.000075 to 0.00015 μg/ml). Footpad swelling decreased more rapidly in mice treated with Q203-containing regimens than in mice treated with RIF and STR (RIF+STR) and RPT and CFZ (RPT+CFZ). Nearly all footpads were culture negative after only 2 weeks of treatment with regimens containing RPT, CFZ, and Q203. No relapse was detected after only 2 weeks of treatment in mice treated with any of the Q203-containing regimens. In contrast, 15% of mice receiving RIF+STR for 4 weeks relapsed. We conclude that it may be possible to cure patients with Buruli ulcer in 14 days or less using Q203-containing regimens rather than currently recommended 56-day regimens.
Topics: Animals; Anti-Bacterial Agents; Bacterial Load; Buruli Ulcer; Clarithromycin; Clofazimine; Disease Models, Animal; Drug Resistance, Bacterial; Drug Therapy, Combination; Electron Transport; Humans; Imidazoles; Mice, Inbred BALB C; Microbial Sensitivity Tests; Mycobacterium ulcerans; Piperidines; Pyridines; Rifampin; Streptomycin
PubMed: 31036687
DOI: 10.1128/AAC.00426-19 -
Molecular Cell Aug 2020Protein secretion in eukaryotes and prokaryotes involves a universally conserved protein translocation channel formed by the Sec61 complex. Unrelated small-molecule...
Protein secretion in eukaryotes and prokaryotes involves a universally conserved protein translocation channel formed by the Sec61 complex. Unrelated small-molecule natural products and synthetic compounds inhibit Sec61 with differential effects for different substrates or for Sec61 from different organisms, making this a promising target for therapeutic intervention. To understand the mode of inhibition and provide insight into the molecular mechanism of this dynamic translocon, we determined the structure of mammalian Sec61 inhibited by the Mycobacterium ulcerans exotoxin mycolactone via electron cryo-microscopy. Unexpectedly, the conformation of inhibited Sec61 is optimal for substrate engagement, with mycolactone wedging open the cytosolic side of the lateral gate. The inability of mycolactone-inhibited Sec61 to effectively transport substrate proteins implies that signal peptides and transmembrane domains pass through the site occupied by mycolactone. This provides a foundation for understanding the molecular mechanism of Sec61 inhibitors and reveals novel features of translocon function and dynamics.
Topics: Animals; Binding Sites; Cell-Free System; Dogs; Gene Expression; HCT116 Cells; HEK293 Cells; Humans; Macrolides; Microsomes; Molecular Dynamics Simulation; Mutation; Mycobacterium ulcerans; Pancreas; Protein Binding; Protein Conformation, alpha-Helical; Protein Conformation, beta-Strand; Protein Interaction Domains and Motifs; Protein Transport; Ribosomes; SEC Translocation Channels; Structural Homology, Protein; Substrate Specificity
PubMed: 32692975
DOI: 10.1016/j.molcel.2020.06.013 -
Tropical Medicine and Infectious Disease Jul 2019Uncertainty regarding transmission pathways and control measures makes prompt presentation and diagnosis for Buruli ulcer critical. To examine presentation and diagnosis...
Uncertainty regarding transmission pathways and control measures makes prompt presentation and diagnosis for Buruli ulcer critical. To examine presentation and diagnosis delays in Victoria, Australia, we conducted a retrospective study of 703 cases notified between 2011 and 2017, classified as residing in an endemic (Mornington Peninsula; Bellarine Peninsula; South-east Bayside and Frankston) or non-endemic area. Overall median presentation delay was 30 days (IQR 14-60 days), with no significant change over the study period ( = 0.11). There were significant differences in median presentation delay between areas of residence ( = 0.02), but no significant change over the study period within any area. Overall median diagnosis delay was 10 days (IQR 0-40 days), with no significant change over the study period ( = 0.13). There were significant differences in median diagnosis delay between areas ( < 0.001), but a significant decrease over time only on the Mornington Peninsula ( < 0.001). On multivariable analysis, being aged <15 or >65 years; having non-ulcerative disease; and residing in the Bellarine Peninsula or South-East Bayside (compared to non-endemic areas) were significantly associated with shorter presentation delay. Residing in the Bellarine or Mornington Peninsula and being notified later in the study period were significantly associated with shorter diagnosis delay. To reduce presentation and diagnosis delays, awareness of Buruli ulcer must be raised with the public and medical professionals, particularly those based outside established endemic areas.
PubMed: 31277453
DOI: 10.3390/tropicalmed4030100 -
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 -
Medecine Tropicale Et Sante... Mar 2023Source of many myths, French Guiana represents an exceptional territory due to the richness of its biodiversity and the variety of its communities. The only European... (Review)
Review
Source of many myths, French Guiana represents an exceptional territory due to the richness of its biodiversity and the variety of its communities. The only European territory in Amazonia, surrounded by the Brazilian giant and the little-known Suriname, Ariane 6 rockets are launched from Kourou while 50% of the population lives below the poverty line. This paradoxical situation is a source of health problems specific to this territory, whether they be infectious diseases with unknown germs, intoxications or chronic pathologies.Some infectious diseases such as Q fever, toxoplasmosis, cryptococcosis or HIV infection are in common with temperate countries, but present specificities leading to sometimes different management and medical reasoning. In addition to these pathologies, many tropical diseases are present in an endemic and / or epidemic mode such as malaria, leishmaniasis, Chagas disease, histoplasmosis or dengue. Besides, Amazonian dermatology is extremely varied, ranging from rare but serious pathologies (Buruli ulcer, leprosy) to others which are frequent and benign such as agouti lice (mites of the family Trombiculidae) or papillonitis. Envenomations by wild fauna are not rare, and deserve an appropriate management of the incriminated taxon. Obstetrical, cardiovascular and metabolic cosmopolitan pathologies sometimes take on a particular dimension in French Guiana that must be taken into account in the management of patients. Finally, different types of intoxication are to be known by practitioners, especially due to heavy metals.European-level resources offer diagnostic and therapeutic possibilities that do not exist in the surrounding countries and regions, thus allowing the management of diseases that are not well known elsewhere.Thanks to these same European-level resources, research in Guyana occupies a key place within the Amazon region, despite a smaller population than in the surrounding countries. Thus, certain pathologies such as histoplasmosis of the immunocompromised patient, Amazonian toxoplasmosis or Q fever are hardly described in neighboring countries, probably due to under-diagnosis linked to more limited resources. French Guiana plays a leading role in the study of these diseases.The objective of this overview is to guide health care providers coming to or practicing in French Guiana in their daily practice, but also practitioners taking care of people returning from French Guiana.
Topics: Animals; Humans; Communicable Diseases; Cuniculidae; French Guiana; Histoplasmosis; HIV Infections; Noncommunicable Diseases; Q Fever; Toxoplasmosis
PubMed: 37389381
DOI: 10.48327/mtsi.v3i1.2023.308 -
PLOS Global Public Health 2022Buruli ulcer is a neglected tropical disease caused by M. ulcerans, an environmental mycobacterium. This cutaneous infectious disease affects populations with poor...
A combined field study of Buruli ulcer disease in southeast Benin proposing preventive strategies based on epidemiological, geographic, behavioural and environmental analyses.
Buruli ulcer is a neglected tropical disease caused by M. ulcerans, an environmental mycobacterium. This cutaneous infectious disease affects populations with poor access to sanitation, safe water and healthcare living in rural areas of West and Central Africa. Stagnant open bodies of surface water and slow-running streams are the only risk factor identified in Africa, and there is no human-to-human transmission. Appropriate and effective prevention strategies are required for populations living in endemic areas. Based on a multidisciplinary approach in an area in which Buruli ulcer is endemic in South Benin, we investigated the link between all human-environment interactions relating to unprotected water and behaviors associated with Buruli ulcer risk likely to affect incidence rates. We characterised the sources of water as well as water bodies and streams used by communities, by conducting a prospective case-control study directly coupled with geographic field observations, spatial analysis, and the detection of M. ulcerans in the environment. A full list of the free surface waters used for domestic activities was generated for a set of 34 villages, and several types of human behaviour associated with a higher risk of transmission were identified: (i) prolonged walking in water to reach cultivated fields, (ii) collecting water, (iii) and swimming. Combining the results of the different analyses identified the risk factor most strongly associated with Buruli ulcer was the frequency of contact with unprotected and natural water, particularly in regularly flooded or irrigated lowlands. We confirm that the use of clean water from drilled wells confers protection against Buruli ulcer. These specific and refined results provide a broader scope for the design of an appropriate preventive strategy including certain practices or infrastructures observed during our field investigations. This strategy could be improved by the addition of knowledge about irrigation practices and agricultural work in low-lying areas.
PubMed: 36962132
DOI: 10.1371/journal.pgph.0000095 -
Methods in Molecular Biology (Clifton,... 2022As acknowledged by the Clinical and Laboratory Standards Institute (CLSI), there is an insufficient evidence base on which to recommend a standard method for...
As acknowledged by the Clinical and Laboratory Standards Institute (CLSI), there is an insufficient evidence base on which to recommend a standard method for antimicrobial susceptibility testing against M. ulcerans. The agar proportion method has been recognized as the standard method for susceptibility testing against Mycobacterium tuberculosis complex (MTBC) isolates for decades (Woods GL, Engenack NL, Lin G, Turnidge JD (2018) CLSI standards: guidelines for health care excellence. Susceptibility testing of mycobacteria, Nocardia spp., and other aerobic Actinomycetes, 3rd edn. Clinical and Laboratory Standards Institute Copyright©2018 Clinical and Laboratory Standards Institute, Wayne (PA)). While it is more labor-intensive and requires larger amounts of drug or compound than broth-based testing, we recommend the agar proportion method for determination of minimum inhibitory concentrations against M. ulcerans. Herewith we present the method we implemented in our laboratory over the last 2 decades.
Topics: Agar; Anti-Bacterial Agents; Microbial Sensitivity Tests; Mycobacterium ulcerans; Pharmaceutical Preparations
PubMed: 34643913
DOI: 10.1007/978-1-0716-1779-3_18