Stable and Local Reservoirs of Mycobacterium ulcerans Inferred from the Nonrandom Distribution of Bacterial Genotypes, Benin.
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ABSTRACT:
SUBMITTER: Coudereau C
PROVIDER: S-EPMC7045821 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundBuruli ulcer is a neglected tropical disease caused by Mycobacterium ulcerans, an environmental mycobacterium. Although transmission of M. ulcerans remains poorly understood, the main identified risk factor for acquiring Buruli ulcer is living in proximity of potentially contaminated water sources. Knowledge about the clinical features of Buruli ulcer and its physiopathology is increasing, but little is known about recurrence due to reinfection.Methodology/principal findingsWe describe two patients with Buruli ulcer recurrence due to reinfection with M. ulcerans, as demonstrated by comparisons of DNA from the strains isolated at the time of the first diagnosis and at recurrence. Based on the spatial distribution of M. ulcerans genotypes in this region and a detailed study of the behavior of these two patients with respect to sources of water as well as water bodies and streams, we formulated hypotheses concerning the sites at which they may have been contaminated.Conclusions/significanceSecond episodes of Buruli ulcer may occur through reinfection, relapse or a paradoxical reaction. We formally demonstrated that the recurrence in these two patients was due to reinfection. Based on the sites at which the patients reported engaging in activities relating to water, we were able to identify possible sites of contamination. Our findings indicate that the non-random distribution of M. ulcerans genotypes in this region may provide useful information about activities at risk.
| S-EPMC8746791 | biostudies-literature
Project description:Efforts to control the spread of Buruli ulcer--an 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 30 km2 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 5.2 Mbp 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 M. ulcerans thus might include humans, or perhaps M. ulcerans-infected animals such as livestock that move regularly between countries.
| S-EPMC4380315 | biostudies-literature
Project description:BackgroundMycobacterium ulcerans is the causative agent of Buruli ulcer (BU). In West Africa there is an association between BU and residence in low-lying rural villages where aquatic sources are plentiful. Infection occurs through unknown environmental exposure; human-to-human infection is rare. Molecular evidence for M. ulcerans in environmental samples is well documented, but the association of M. ulcerans in the environment with Buruli ulcer has not been studied in West Africa in an area with accurate case data.Methodology/principal findingEnvironmental samples were collected from twenty-five villages in three communes of Benin. Sites sampled included 12 BU endemic villages within the Ouheme and Couffo River drainages and 13 villages near the Mono River and along the coast or ridge where BU has never been identified. Triplicate water filtrand samples from major water sources and samples from three dominant aquatic plant species were collected. Detection of M. ulcerans was based on quantitative polymerase chain reaction. Results show a significant association between M. ulcerans in environmental samples and Buruli ulcer cases in a village (p = 0.0001). A "dose response" was observed in that increasing numbers of M. ulceran- positive environmental samples were associated with increasing prevalence of BU cases (R(2) = 0.586).Conclusions/significanceThis study provides the first spatial data on the overlap of M. ulcerans in the environment and BU cases in Benin where case data are based on active surveillance. The study also provides the first evidence on M. ulcerans in well-defined non-endemic sites. Most environmental pathogens are more broadly distributed in the environment than in human populations. The congruence of M. ulcerans in the environment and human infection raises the possibility that humans play a role in the ecology of M. ulcerans. Methods developed could be useful for identifying new areas where humans may be at high risk for BU.
| S-EPMC3269429 | biostudies-literature
Project description:BackgroundGenotyping 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.MethodsEnvironmental 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 sequences (IS2404, IS2606, KR-B). Positive samples to MU were further genotyped by VNTR with confirmation by sequencing of four loci (MIRU1, Locus 6, ST1, Locus 19).ResultsMU was detected in environmental samples including water bodies (23%), biofilms (14%), detritus (10%), and in human patients (73%). MU genotypes D, W, and C were found both in environmental and human samples. The micro geo-distribution of MU genotypes from communities showed that genotype D is found both in environmental and human samples, while genotypes W and C are specific to environmental samples and human lesions, respectively. No obvious focal grouping of MU genotypes was observed at the community scale. An additional survey in the human microhabitat suggests that domestic and wild animals do not shed MU in their saliva and feces in sampled communities.ConclusionsVNTR typing uncovered different MU genotypes circulating in the endemic communities of the Akonolinga district. A MU environmental genotype was found in patients, yet the mechanism of contamination remains to be investigated; and recovering MU in culture from the environment remains key priority to enable a better understanding of the mode of transmission of BU. We also conclude that excretions from suspected animals are unlikely to be major sources of MU in the Nyong Valley in Cameroon.
| S-EPMC8139057 | biostudies-literature
Project description:Mycobacterium ulcerans is an emerging environmental pathogen that causes debilitating, ulcerative disease in humans and other vertebrates. The majority of human cases occur in tropical and temperate regions of Africa and Australia, and outbreaks of piscine mycobacteriosis caused by M. ulcerans have been reported in disparate geographic locations spanning the globe. While exposure to a natural body of water is the most common risk factor for human infection, the environmental distribution of M. ulcerans in aquatic habitats has not been extensively studied. Although no human cases have been reported in the United States, a strain of M. ulcerans has been identified as the cause of a piscine mycobacteriosis in Striped bass (Morone saxatilis) within the Chesapeake Bay. Infected fish exhibit bright red ventral and lateral dermal lesions. We observed a possible outbreak causing similar lesions on red drum (Sciaenops ocellatus) in wetlands of southern Louisiana and detected M. ulcerans-specific genetic markers in lesion samples from these fish. Based on these findings, we studied the geographic and seasonal prevalence of these markers across southern Louisiana. M. ulcerans was detected in each of the nine areas sampled across the state. M. ulcerans prevalence was significantly lower in the fall samples, and the low prevalence coincided with decreased nutrient levels and an increase in water temperature. To our knowledge, this is the first study of M. ulcerans biomarkers in the southern United States.
| S-EPMC3623173 | biostudies-literature
Project description:Currently, there are only two publicly available genomes of Mycobacterium ulcerans-the causative agent of the neglected, but devastating, tropical disease Buruli ulcer. Here, we report the draft genome sequence of isolate S4018, recovered from an active cutaneous lesion of a patient with Buruli ulcer in Benin, Africa.
| S-EPMC5408113 | biostudies-literature
Project description:ObjectiveTo investigate the distribution of Mycobacterium tuberculosis genotypes across Africa.MethodsThe SITVIT2 global repository and PUBMED were searched for spoligotype and published genotype data respectively, of M. tuberculosis from Africa. M. tuberculosis lineages in Africa were described and compared across regions and with those from 7 European and 6 South-Asian countries. Further analysis of the major lineages and sub-lineages using Principal Component analysis (PCA) and hierarchical cluster analysis were done to describe clustering by geographical regions. Evolutionary relationships were assessed using phylogenetic tree analysis.ResultsA total of 14727 isolates from 35 African countries were included in the analysis and of these 13607 were assigned to one of 10 major lineages, whilst 1120 were unknown. There were differences in geographical distribution of major lineages and their sub-lineages with regional clustering. Southern African countries were grouped based on high prevalence of LAM11-ZWE strains; strains which have an origin in Portugal. The grouping of North African countries was due to the high percentage of LAM9 strains, which have an origin in the Eastern Mediterranean region. East African countries were grouped based on Central Asian (CAS) and East-African Indian (EAI) strain lineage possibly reflecting historic sea trade with Asia, while West African Countries were grouped based on Cameroon lineage of unknown origin. A high percentage of the Haarlem lineage isolates were observed in the Central African Republic, Guinea, Gambia and Tunisia, however, a mixed distribution prevented close clustering.ConclusionsThis study highlighted that the TB epidemic in Africa is driven by regional epidemics characterized by genetically distinct lineages of M. tuberculosis. M. tuberculosis in these regions may have been introduced from either Europe or Asia and has spread through pastoralism, mining and war. The vast array of genotypes and their associated phenotypes should be considered when designing future vaccines, diagnostics and anti-TB drugs.
| S-EPMC6070189 | biostudies-literature
Project description:BackgroundCurrent 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 findingsHere we analyzed AFB positive tissue samples (n = 83) for the presence, distribution and amount of AFB. AFB were nearly exclusively present in the subcutis with large extracellular clusters being most frequently (67%) found in plaque lesions. In ulcerative lesions small clusters and dispersed AFB were more common. Beside this, 151 swab samples from 37 BU patients were analyzed by IS2404 qPCR and ZN staining in parallel. The amount of M. ulcerans DNA in extracts from swabs correlated well with the probability of finding AFB in direct smear microscopy, with 56.1% of the samples being positive in both methods and 43.9% being positive only in qPCR. By analyzing three swabs per patient instead of one, the probability to have at least one positive swab increased from 80.2% to 97.1% for qPCR and from 45% to 66.1% for AFB smear examination.Conclusion / significanceOur data show that M. ulcerans bacteria are primarily located in the subcutis of BU lesions, making the retrieval of the deep subcutis mandatory for examination of tissue samples for AFB. When laboratory diagnosis is based on the recommended less invasive collection of swab samples, analysis of three swabs from different areas of ulcerative lesions instead of one increases the sensitivity of both qPCR and of smear microscopy substantially.
| S-EPMC4890796 | biostudies-literature
Project description:Buruli ulcer, caused by Mycobacterium ulcerans, is highly endemic in West Africa. While the mode of transmission is unknown, many studies associate Buruli ulcer with different types of water exposure. We present results from the largest study to date to test for M. ulcerans in aquatic sites and identify environmental attributes associated with its presence. Environmental samples from 98 aquatic sites in the Greater Accra, Ashanti, and Volta regions of Ghana were tested for the presence of M. ulcerans DNA by polymerase chain reaction. The proportion of aquatic sites positive for M. ulcerans varied by region: Ashanti 66% (N = 39), Greater Accra 34% (N = 29), and Volta 0% (N = 30). We explored the spatial distribution of M. ulcerans positive and negative water bodies and found no significant clusters. We also determined both highly localized water attributes and broad scale remotely sensed land cover and terrain environmental characteristics associated with M. ulcerans presence through logistic regression. Our results concur with published results regarding conditions suitable for M. ulcerans growth and associations with Buruli ulcer disease burden with regards to water characteristics and disturbed environments, but differ from others with regards to spatial associations and topographic effects such as elevation and wetness. While our results suggest M. ulcerans is an environmental organism existing in a specific ecological niche, they also reveal variation in the elements defining this niche across the sites considered. In addition, despite the causal association between Buruli ulcer and M. ulcerans, we observed no significant statistical association between case reports of Buruli ulcer and presence of M. ulcerans in nearby waterbodies.
| S-EPMC5402941 | biostudies-literature
Project description:Whether Mycobacterium ulcerans, the etiological agent of Buruli ulcer in numerous tropical countries, would exist in a dormant state as reported for closely related Mycobacterium species, has not been established. Six M. ulcerans strains were exposed to a progressive depletion in oxygen for 2 months, using the Wayne model of dormancy previously described for M. tuberculosis, and further examined by microscopy after staining of dynamic, dormant, and dead mycobacteria (DDD staining), microcalorimetry and subculture in the presence of dead and replicative M. ulcerans as controls. Mycobacterium ulcerans CU001 strain died during the progressive oxygen depletion and four of five remaining strains exhibited Nile red-stained intracellular lipid droplets and a 14- to 20-day regrowth when exposed to ambient air, consistent with dormancy. A fifth M. ulcerans 19423 strain stained negative in DDD staining and slowly regrew in 27 days. Three tested M. ulcerans strains yielded microcalorimetric pattern similar to that of the negative (dead) homologous controls, differing from that of the homologous positive (replicative) controls. The relevance of these experimental observations, suggesting a previously unreported dormancy state of M. ulcerans, warrants further investigations in the natural ecological niches where M. ulcerans thrive as well as in Buruli ulcer lesions.
| S-EPMC9294675 | biostudies-literature