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Buruli Ulcer

M L Sanders, H R Jordan, C Serewis-Pond, L Zheng, M E Benbow, P L Small, J K Tomberlin
The ecological functions of many toxins continue to remain unknown for those produced by environmental pathogens. Mycobacterium ulcerans, the causative agent of the neglected tropical disease, Buruli ulcer, produces a cytotoxic macrolide, mycolactone, whose function(s) in the environment remains elusive. Through a series of dual-choice behavior assays, we show that mycolactone may be an interkingdom cue for the yellow fever mosquito, Aedes aegypti, seeking blood-meals as well as oviposition sites. Results provide novel insight into the evolution between bacteria and potential vectors...
December 1, 2016: Environmental Microbiology
Angèle Bénard, Claudia Sala, Gerd Pluschke
Buruli Ulcer is a neglected tropical disease leading to extensive disabilities and morbidity in West Africa. In this paper we sought to characterize various strains of Mycobacterium ulcerans (M.ulcerans) with different origins and laboratory passage records while refining a mouse model for Buruli ulcer. We described, compared and followed the kinetics of the histo-pathological outcome of infection of a collection of strains at various anatomical sites of infection in order to find a suitable model for further immunization studies...
2016: PloS One
Christina M Steffen, Helen Freeborn
BACKGROUND: Mycobacterium ulcerans infection (Buruli ulcer) is the third most common mycobacterial disease in humans, with presentations ranging from self-limiting skin nodules and ulcers to aggressive infiltrative infections with extensive oedema, fat and skin necrosis. The two foci in Australia are in Victoria and Far North Queensland. We present the 2009-2015 case series for the Queensland focus with special reference to the 2011 spike of 64 cases. METHODS: This case series is based on a combination of prospectively and retrospectively collected data on 95 confirmed cases of M...
November 1, 2016: ANZ Journal of Surgery
Anthony O Meka, Joseph N Chukwu, Charles C Nwafor, Daniel C Oshi, Nelson O Madichie, Ngozi Ekeke, Moses C Anyim, Chukwuka Alphonsus, Obinna Mbah, Glory C Uzoukwa, Martin Njoku, Kentigern Ntana, Kingsley N Ukwaja
BACKGROUND: Delayed diagnosis of Buruli ulcer can worsen clinical presentation of the disease, prolong duration of management, and impose avoidable additional costs on patients and health providers. We investigated the profile, delays in diagnosis, duration of hospitalisation, and associated factors among patients with Buruli ulcer in Nigeria. METHODS: This was a prospective cohort study of patients with Buruli ulcer who were identified from a community-based survey...
October 23, 2016: Transactions of the Royal Society of Tropical Medicine and Hygiene
Samuel A Sakyi, Samuel Yaw Aboagye, Isaac Darko Otchere, Albert M Liao, Thomas G Caltagirone, Dorothy Yeboah-Manu
BACKGROUND: Buruli ulcer (BU) is a subcutaneous skin disease listed among the neglected tropical diseases by the World Health Organization (WHO). Early case detection and management is very important to reduce morbidity and the accompanied characteristic disfiguring nature of BU. Since diagnosis based on clinical evidence can lead to misdiagnosis, microbiological confirmation is essential to reduce abuse of drugs; since the anti-mycobacterial drugs are also used for TB treatment. The current WHO gold standard PCR method is expensive, requires infrastructure and expertise are usually not available at the peripheral centers where BU cases are managed...
October 2016: PLoS Neglected Tropical Diseases
Aurélie Chauffour, Jérôme Robert, Nicolas Veziris, Alexandra Aubry, Vincent Jarlier
BACKGROUND: The treatment of Buruli ulcer (BU) that is caused by Mycobacterium ulcerans, is currently based on a daily administration of rifampin and streptomycin (RIF-STR). A fully oral intermittent regimen would greatly simplify its treatment on the field. METHODOLOGY/PRINCIPAL FINDINGS: The objective of this study was to assess the bactericidal and sterilizing activities of intermittent oral regimens in a murine model of established M. ulcerans infection. Regimens combining rifapentine (RFP 20 mg/kg) with either moxifloxacin (MXF 200 mg/kg), clarithromycin (CLR 100 mg/kg) or bedaquiline (BDQ 25 mg/kg) were administrated twice (2/7) or three (only for RFP-CLR 3/7) times weekly during 8 weeks...
October 2016: PLoS Neglected Tropical Diseases
Mitsunori Yoshida, Kazue Nakanaga, Yoshitoshi Ogura, Atsushi Toyoda, Tadasuke Ooka, Yuko Kazumi, Satoshi Mitarai, Norihisa Ishii, Tetsuya Hayashi, Yoshihiko Hoshino
Mycobacterium ulcerans subsp. shinshuense produces mycolactone and causes Buruli ulcer. Here, we report the complete sequence of its genome, which comprises a 5.9-Mb chromosome and a 166-kb plasmid (pShT-P). The sequence will represent the essential data for future phylogenetic and comparative genome studies of mycolactone-producing mycobacteria.
September 29, 2016: Genome Announcements
Rebecca J Woolley, Anita Velink, Richard O Phillips, William A Thompson, K Mohammed Abass, Tjip S van der Werf, Janine de Zeeuw, Ymkje Stienstra
Buruli ulcer (BU) is one of the 17 neglected tropical diseases for which the World Health Organization has adopted resolutions to improve treatment. BU was previously described as a relatively painless condition; however, recent research has indicated that some patients experience substantial pain. The objective of this study was to explore patients' experiences of pain and their expectations for its treatment. Semistructured interviews were conducted in a BU-endemic region of Ghana. Interviews were held with former BU patients (N = 20) and community controls (N = 19)...
November 2, 2016: American Journal of Tropical Medicine and Hygiene
Noriko Shinoda, Hajime Nakamura, Mineo Watanabe
BACKGROUND: Buruli ulcer is a severe skin disease caused by Mycobacterium ulcerans. Real-time PCR targeting the IS2404 sequence has been used as a reliable and rapid method for the diagnosis of Buruli ulcer and detection of M. ulcerans in the environment. The genome of M. ulcerans contains hundreds of IS2404 copies, which have variability in certain sequences. Therefore, the design of new primers specific to conserved IS2404 regions may potentially improve the sensitivity of M. ulcerans detection and, consequently, the diagnosis of Buruli ulcer, thus ensuring timely treatment of the disease...
2016: Tropical Medicine and Health
G Kpeli, I Darko Otchere, A Lamelas, A L Buultjens, D Bulach, S L Baines, T Seemann, S Giulieri, Z Nakobu, S Y Aboagye, E Owusu-Mireku, G Pluschke, T P Stinear, D Yeboah-Manu
We have previously shown that secondary infections of Buruli ulcer wounds were frequently caused by Staphylococcus aureus. To gain understanding into possible routes of secondary infection, we characterized S. aureus isolates from patient lesions and surrounding environments across two Ghanaian health centres. One hundred and one S. aureus isolates were isolated from wounds (n = 93, 92.1%) and the hospital environment (n = 8, 7.9%) and characterized by the spa gene, mecA and the Panton-Valentine leucocidin toxin followed by spa sequencing and whole genome sequencing of a subset of 49 isolates...
September 2016: New Microbes and New Infections
S Klis, R A Kingma, W Tuah, T S van der Werf, Y Stienstra
OBJECTIVES: Buruli ulcer (BU) is a tropical skin disease caused by infection with Mycobacterium ulcerans, which is currently treated with 8 weeks of streptomycin and rifampicin. The evidence to treat BU for a duration of 8 weeks is limited; a recent retrospective study from Australia suggested that a shorter course of antimicrobial therapy might be equally effective. We studied the outcomes of BU in a cohort of Ghanaian patients who defaulted from treatment and as such received less than 8 weeks of antimicrobial therapy...
September 2016: Tropical Medicine & International Health: TM & IH
Eric Koka, Dorothy Yeboah-Manu, Daniel Okyere, Philip Baba Adongo, Collins K Ahorlu
BACKGROUND: This study was conducted with the aim to understand some of the cultural belief systems in the management of wounds and patients practices that could contaminate wounds at the Obom sub-district of the Ga South Municipality of Ghana. METHODS: This was an ethnographic study using in-depth interviews, Focus Group Discussions and participant observation techniques for data collection. Observations were done on Buruli ulcer patients to document how they integrate local and modern wound management practices in the day-to-day handling of their wounds...
July 2016: PLoS Neglected Tropical Diseases
Araceli Lamelas, Kobina Assan Ampah, Samuel Aboagye, Sarah Kerber, Emelia Danso, Adwoa Asante-Poku, Prince Asare, Julian Parkhill, Simon R Harris, Gerd Pluschke, Dorothy Yeboah-Manu, Katharina Röltgen
In recent years, comparative genome sequence analysis of African Mycobacterium ulcerans strains isolated from Buruli ulcer (BU) lesion specimen has revealed a very limited genetic diversity of closely related isolates and a striking association between genotype and geographical origin of the patients. Here, we compared whole genome sequences of five M. ulcerans strains isolated in 2004 or 2013 from BU lesions of four residents of the Offin river valley with 48 strains isolated between 2002 and 2005 from BU lesions of individuals residing in the Densu river valley of Ghana...
July 2016: PLoS Neglected Tropical Diseases
Samuel A Sakyi, Samuel Y Aboagye, Isaac Darko Otchere, Dorothy Yeboah-Manu
Background. Buruli ulcer (BU) is a necrotizing cutaneous infection caused by Mycobacterium ulcerans. Early diagnosis is crucial to prevent morbid effects and misuse of drugs. We review developments in laboratory diagnosis of BU, discuss limitations of available diagnostic methods, and give a perspective on the potential of using aptamers as point-of-care. Methods. Information for this review was searched through PubMed, web of knowledge, and identified data up to December 2015. References from relevant articles and reports from WHO Annual Meeting of the Global Buruli Ulcer initiative were also used...
2016: Canadian Journal of Infectious Diseases & Medical Microbiology
Sandra Simões, Manuela Carvalheiro, Maria Manuela Gaspar
Infectious diseases in the skin represent a major group of pathologies that contribute annually for significant health economic expenses. According to WHO, Buruli Ulcer (BU) and Cutaneous Leishmaniasis (CL) are two neglected tropical diseases for which therapy remains inadequate. Topical delivery of therapeutics constitutes an advantageous alternative to treat infected skin lesions as it allows a direct treatment of affected areas avoiding unwanted systemic effects and reducing the drug dosage. However, effective topical delivery of antimicrobial agents is still a challenge...
June 30, 2016: Current Pharmaceutical Design
Arnaud Setondji Amoussouhoui, Roch Christian Johnson, Ghislain Emmanuel Sopoh, Ines Elvire Agbo, Paulin Aoulou, Jean-Gabin Houezo, Albert Tingbe-Azalou, Micah Boyer, Mark Nichter
BACKGROUND: Reducing social distance between hospital staff and patients and establishing clear lines of communication is a major challenge when providing in-patient care for people afflicted by Buruli ulcer (BU) and chronic ulcers. Research on hospitals as therapeutic communities is virtually non-existent in Africa and is currently being called for by medical anthropologists working in the field of health service and policy planning. This paper describes a pioneering attempt to establish a therapeutic community for patients suffering from BU and other chronic ulcers requiring long term hospital care in Benin...
July 2016: PLoS Neglected Tropical Diseases
Aaron Morris, Jean-François Guégan, M Eric Benbow, Heather Williamson, Pamela L C Small, Charles Quaye, Daniel Boakye, Richard W Merritt, Rodolphe E Gozlan
Emerging infectious disease outbreaks are increasingly suspected to be a consequence of human pressures exerted on natural ecosystems. Previously, host taxonomic communities have been used as indicators of infectious disease emergence, and the loss of their diversity has been implicated as a driver of increased presence. The mechanistic details in how such pathogen-host systems function, however, may not always be explained by taxonomic variation or loss. Here we used machine learning and methods based on Gower's dissimilarity to quantify metrics of invertebrate functional diversity, in addition to functional groups and their taxonomic diversity at sites endemic and non-endemic for the model generalist pathogen Mycobacterium ulcerans, the causative agent of Buruli ulcer...
June 29, 2016: EcoHealth
U Anand, M Sinisi, M Fox, A MacQuillan, T Quick, Y Korchev, C Bountra, T McCarthy, P Anand
BACKGROUND: Mycolactone is a polyketide toxin secreted by the mycobacterium Mycobacterium ulcerans, responsible for the extensive hypoalgesic skin lesions characteristic of patients with Buruli ulcer. A recent pre-clinical study proposed that mycolactone may produce analgesia via activation of the angiotensin II type 2 receptor (AT2R). In contrast, AT2R antagonist EMA401 has shown analgesic efficacy in animal models and clinical trials for neuropathic pain. We therefore investigated the morphological and functional effects of mycolactone in cultured human and rat dorsal root ganglia (DRG) neurons and the role of AT2R using EMA401...
2016: Molecular Pain
Nicholas J Tobias, Nana Ama Ammisah, Evans K Ahortor, John R Wallace, Anthony Ablordey, Timothy P Stinear
Identifying the source reservoirs of Mycobacterium ulcerans is key to understanding the mode of transmission of this pathogen and controlling the spread of Buruli ulcer (BU). In Australia, the native possum can harbor M. ulcerans in its gastrointestinal tract and shed high concentrations of the bacteria in its feces. To date, an analogous animal reservoir in Africa has not been identified. Here we tested the hypothesis that common domestic animals in BU endemic villages of Ghana are reservoir species analogous to the Australian possum...
2016: PeerJ
Marie-Thérèse Ruf, Miriam Bolz, Moritz Vogel, Pierre F Bayi, Martin W Bratschi, Ghislain Emmanuel Sopho, Dorothy Yeboah-Manu, Alphonse Um Boock, Thomas Junghanss, Gerd Pluschke
BACKGROUND: Current laboratory diagnosis of Buruli ulcer (BU) is based on microscopic detection of acid fast bacilli, quantitative real-time PCR (qPCR), histopathology or cultivation. Insertion sequence (IS) 2404 qPCR, the most sensitive method, is usually only available at reference laboratories. The only currently available point-of-care test, microscopic detection of acid fast bacilli (AFB), has limited sensitivity and specificity. METHODOLOGY/ PRINCIPAL FINDINGS: Here we analyzed AFB positive tissue samples (n = 83) for the presence, distribution and amount of AFB...
June 2016: PLoS Neglected Tropical Diseases
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