Source Tracking Mycobacterium ulcerans Infections in the Ashanti Region, Ghana (original) (raw)
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PLoS Neglected Tropical Diseases, 2010
Buruli ulcer (BU) is an emerging necrotizing disease of the skin and subcutaneous tissue caused by Mycobacterium ulcerans. While proximity to stagnant or slow flowing water bodies is a risk factor for acquiring BU, the epidemiology and mode of M. ulcerans transmission is poorly understood. Here we have used high-throughput DNA sequencing and comparisons of the genomes of seven M. ulcerans isolates that appeared monomorphic by existing typing methods. We identified a limited number of single nucleotide polymorphisms (SNPs) and developed a real-time PCR SNP typing method based on these differences. We then investigated clinical isolates of M. ulcerans on which we had detailed information concerning patient location and time of diagnosis. Within the Densu river basin of Ghana we observed dominance of one clonal complex and local clustering of some of the variants belonging to this complex. These results reveal focal transmission and demonstrate, that micro-epidemiological analyses by SNP typing has great potential to help us understand how M. ulcerans is transmitted.
Frontiers in Microbiology
Buruli ulcer (BU), a necrotic skin disease caused by Mycobacterium ulcerans, is mainly prevalent in West Africa, but cases have also been reported in other tropical parts of the world. It is the second most common mycobacterial disease after tuberculosis in Ghana and Côte d’Ivoire. Heterogeneity among M. ulcerans from different geographical locations has not been clearly elucidated, and some studies seem to suggest genetic differences between M. ulcerans in humans and in the environment. This study aimed at identifying genetic differences among M. ulcerans strains between two BU endemic countries: Ghana and Côte d’Ivoire. Clinical samples consisting of swabs, fine needle aspirates, and tissue biopsies of suspected BU lesions and environmental samples (e.g., water, biofilms from plants, soil, and detrital material) were analyzed. BU cases were confirmed via acid fast staining and PCR targeting the 16S rRNA, IS2404, IS2606, and ER domain genes present on M. ulcerans. Heterogeneity amo...
Tropical Medicine and Health
Background Genotyping is a powerful tool for investigating outbreaks of infectious diseases and it can provide useful information such as identifying the source and route of transmission, and circulating strains involved in the outbreak. Genotyping techniques based on variable number of tandem repeats (VNTR) are instrumental in detecting heterogeneity in Mycobacterium ulcerans (MU) and also for discriminating MU from other mycobacteria species. Here, we describe and map the distribution of MU genotypes in Buruli ulcer (BU) endemic communities of the Nyong valley in Cameroon. We also tested the hypothesis of whether the suspected animal reservoirs of BU that share the human microhabitat are shedding contaminated fecal matters and saliva into their surrounding environments. Methods Environmental samples from suspected MU-risk factors and lesion swabs from human patients were sampled in BU-endemic communities and tested for the presence of MU by qPCR targeting three independent sequenc...
PLOS Neglected Tropical Diseases, 2015
Efforts to control the spread of Buruli ulceran emerging ulcerative skin infection caused by Mycobacterium ulcerans -have been hampered by our poor understanding of reservoirs and transmission. To help address this issue, we compared whole genomes from 18 clinical M. ulcerans isolates from a 30km 2 region within the Asante Akim North District, Ashanti region, Ghana, with 15 other M. ulcerans isolates from elsewhere in Ghana and the surrounding countries of Ivory Coast, Togo, Benin and Nigeria. Contrary to our expectations of finding minor DNA sequence variations among isolates representing a single M. ulcerans circulating genotype, we found instead two distinct genotypes. One genotype was closely related to isolates from neighbouring regions of Amansie West and Densu, consistent with the predicted local endemic clone, but the second genotype (separated by 138 single nucleotide polymorphisms [SNPs] from other Ghanaian strains) most closely matched M. ulcerans from Nigeria, suggesting another introduction of M. ulcerans to Ghana, perhaps from that country. Both the exotic genotype and the local Ghanaian genotype displayed highly restricted intra-strain genetic variation, with less than 50 SNP differences across a 5.2Mbp core genome within each genotype. Interestingly, there was no discernible spatial clustering of genotypes at the local village scale. Interviews revealed no obvious epidemiological links among BU patients who had been infected with identical M. ulcerans genotypes but lived in geographically separate villages. We conclude that M. ulcerans is spread widely across the region, with multiple genotypes present in any one area. These data give us new perspectives on the behaviour of possible reservoirs and subsequent transmission mechanisms of M. ulcerans. These observations also show for the first time that M. ulcerans can be mobilized, introduced to a new area and then spread within a population. Potential reservoirs of PLOS Neglected Tropical Diseases |
Emerging Infectious Diseases
B uruli ulcer (BU) is a devastating necrotic human skin disease caused by Mycobacterium ulcerans (1). It is the third most common mycobacterial disease after tuberculosis and leprosy; ≈2,000 cases are reported each year worldwide, mostly in rural areas of West and Central Africa. The high number of patients with massive skin ulcers is a major problem because treatment of advanced disease is complex, and the consequent long-term disabilities can lead to social stigmatization and economic consequences for families and rural communities (2). BU is characterized by a focal endemicity, and M. ulcerans has potential primary environmental reservoirs in wetlands, rivers, and stagnant bodies of water (3,4). The exact mode of transmission to humans remains unclear, but studies have shown that inoculation into the subcutaneous tissues is required (5,6). Thus, suspicions have arisen that aquatic insects, mollusks, and fishes are reservoirs and that insect bites are the mode of transmission (7-9). Transmission through human-to-human contact has been ruled out as a potential mode of transmission because living near an infected family member does not pose a higher risk for infection (10). However, fundamental questions remain concerning the participation of humans in dissemination of the bacterium (11,12). Developing adapted preventive strategies requires identification of the environment that enables M. ulcerans development and the dynamics of the mycobacterium in the environment and in patients. However, because M. ulcerans cannot yet be cultured directly from environmental samples, comparison of M. ulcerans isolates retrieved in the environment with those in humans is impossible. Whole-genome sequencing (WGS), coupled with single-nucleotide polymorphism (SNP)-based genotyping, has led to major advances in M. ulcerans genomics. This approach was applied recently to provide a description of the M. ulcerans population structure in Ghana (13). It has also been used to provide insights into the circulating genotypes in BUendemic regions of Cameroon (14) and to study the evolution of M. ulcerans in Africa and southeastern
PLoS neglected tropical diseases, 2018
Buruli Ulcer (BU) is a neglected tropical skin infection caused by Mycobacterium ulcerans. Residence near aquatic areas has been identified as an important source of transmission of M. ulcerans with increased risk of contracting Buruli ulcer. However, the reservoir and the mode of transmission are not yet well known. The aim of this study was to identify the presence of M. ulcerans in the environment and its relationship with Buruli ulcer occurrence in Zio and Yoto districts of the maritime region in south Togo. A total of 219 environmental samples including soil (n = 119), water (n = 65), biofilms/plants (n = 29) and animals' feces (n = 6) were collected in 17 villages of Zio and Yoto districts of the maritime region in Togo. DNA of M. ulcerans including IS2404 and IS2606 insertions sequences and mycolactone ketoreductase-B gene (KR-B) was detected using real time PCR amplification (qPCR) technique. In parallel, clinical samples of patients were tested to establish a comparison...
Journal of Clinical Microbiology, 2009
Mycobacterium ulcerans causes the devastating infectious skin disease Buruli ulcer and has a monomorphic population structure. The resolution of conventional genetic fingerprinting methods is therefore not sufficient for microepidemiological studies aiming to characterize transmission pathways. In a previous comparative genomic hybridization analysis with a microarray covering part of the M. ulcerans genome, we have found extensive insertional-deletional sequence polymorphisms among M. ulcerans isolates of diverse geographic origins that allowed us to distinguish between strains coming from different continents. Since large numbers of insertion sequences are spread over the genome of African M. ulcerans strains, we reasoned that these may drive large sequence polymorphisms in otherwise clonal local mycobacterial populations. In this study, we used a printed DNA microarray covering the whole genome of the Ghanaian M. ulcerans reference strain Agy99 for comparative genomic hybridization. The assay identified multiple regions of difference when DNA of a Japanese M. ulcerans strain was analyzed. In contrast, not a single insertional-deletional genomic variation was found within a panel of disease isolates coming from an area of Ghana where Buruli ulcer is endemic. These results indicate that, despite the expectations deduced from other mycobacterial pathogens, only analyses of single nucleotide polymorphisms will have the potential to differentiate local populations of M. ulcerans.
PLOS Neglected Tropical Diseases, 2008
Mycobacterium ulcerans, the causative agent of Buruli ulcer, is an emerging environmental bacterium in Australia and West Africa. The primary risk factor associated with Buruli ulcer is proximity to slow moving water. Environmental constraints for disease are shown by the absence of infection in arid regions of infected countries. A particularly mysterious aspect of Buruli ulcer is the fact that endemic and non-endemic villages may be only a few kilometers apart within the same watershed. Recent studies suggest that aquatic invertebrate species may serve as reservoirs for M. ulcerans, although transmission pathways remain unknown. Systematic studies of the distribution of M. ulcerans in the environment using standard ecological methods have not been reported. Here we present results from the first study based on random sampling of endemic and non-endemic sites. In this study PCR-based methods, along with biofilm collections, have been used to map the presence of M. ulcerans within 26 aquatic sites in Ghana. Results suggest that M. ulcerans is present in both endemic and non-endemic sites and that variable number tandem repeat (VNTR) profiling can be used to follow chains of transmission from the environment to humans. Our results suggesting that the distribution of M. ulcerans is far broader than the distribution of human disease is characteristic of environmental pathogens. These findings imply that focal demography, along with patterns of human water contact, may play a major role in transmission of Buruli ulcer.
PLoS neglected tropical diseases, 2016
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. While all M. ulcerans isolates from the Densu river valley belonged to the same clonal complex, members of two distinct clonal complexes were found in the Offin river valley over space and time. The Offin strains were closely related to genotypes from either the Densu region or from the Asante Akim North district of Ghana. These results point towards an occasional involvement of a mobile reservoir in the transmiss...