Buruli Ulcer Incidence Research Articles

Impact of Temperature and Oxygen Availability on Gene Expression Patterns of Mycobacterium ulcerans.

Buruli ulcer disease is a neglected tropical disease caused by the environmental pathogen Mycobacterium ulcerans. The M. ulcerans major virulence factor is mycolactone, a lipid cytotoxic compound whose genes are carried on a plasmid. Although an exact reservoir and mode(s) of transmission are unknown, data provide evidence of both. First, Buruli ulcer incidence and M. ulcerans presence have been linked to slow-moving water with low oxygen. M. ulcerans has also been suggested to be sensitive to UV due to termination in crtI, encoding a phytoene dehydrogenase, required for carotenoid production. Further, M. ulcerans has been shown to cause disease following puncture but not when introduced to open abrasion sites, suggesting that puncture is necessary for transmission and pathology. Despite these findings, the function and modulation of mycolactone and other genes in response to dynamic abiotic conditions such as UV, temperature, and oxygen have not been shown. In this study, we investigated modulation of mycolactone and other genes on exposure to changing UV and oxygen microenvironmental conditions. Mycolactone expression was downregulated on exposure to the single stress high temperature and did not change significantly with exposure to UV; however, it was upregulated when exposed to microaerophilic conditions. Mycolactone expression was downregulated under combined stresses of high temperature and low oxygen, but there was upregulation of several stress response genes. Taken together, results suggest that temperature shapes M. ulcerans metabolic response more so than UV exposure or oxygen requirements. These data help to define the environmental niche of M. ulcerans and metabolic responses during initial human infection. IMPORTANCE Buruli ulcer is a debilitating skin disease caused by the environmental pathogen Mycobacterium ulcerans. M. ulcerans produces a toxic compound, mycolactone, which leads to tissue necrosis and ulceration. Barriers to preventing Buruli ulcer include an incomplete understanding of M. ulcerans reservoirs, how the pathogen is transmitted, and under what circumstances mycolactone and other M. ulcerans genes are expressed and produced in its natural environment and in the host. We conducted a study to investigate M. ulcerans gene expression under several individual or combined abiotic conditions. Our data showed that mycolactone expression was downregulated under combined stresses of high temperature and low oxygen but there was upregulation of several stress response genes. These data are among only a few studies measuring modulation of mycolactone and other M. ulcerans genes that could be involved in pathogen fitness in its natural environment and virulence while within the host.

Correlation between Buruli Ulcer Incidence and Vectorborne Diseases, Southeastern Australia, 2000-2020.

Researchers have hypothesized that mosquitoes are vectors involved in Mycobacterium ulcerans transmission. Previous findings of a correlation between incidence of M. ulcerans, which causes Buruli ulcer, and locally acquired vectorborne diseases in southeastern Australia further strengthened this argument. However, our updated data indicate that this correlation has not continued beyond 2008.

Impact of mycolactone produced by Mycobacterium ulcerans on life-history traits of Aedes aegypti (L.) and resulting habitat selection for oviposition.

Buruli ulcer (BU) is a globally recognized, yet largely neglected tropical disease whose etiologic agent is Mycobacterium ulcerans. Although the exact mode of transmission is unclear, epidemiological evidence links BU incidence with slow-moving or stagnant, aquatic habitats, and laboratory-based experiments have shown disease manifestation in animals with dermal punctures. Therefore, hypotheses for transmission include contact with slowmoving aquatic habitats and associated biting aquatic insects, such as mosquitoes. Recent research demonstrated the toxin produced by M. ulcerans, mycolactone, is an attractant for adult mosquitoes seeking a blood-meal as well as oviposition sites. In the study presented here, we examined the impact of mycolactone at different concentrations on immature lifehistory traits of Aedes aegypti, which commonly occurs in the same environment as M. ulcerans. We determined percent egg hatch was not significantly different across treatments. However, concentration impacted the survivorship of larval mosquitoes to the adult stage (p < 0.001). Resulting adults also showed a slight preference, but not significant (p > 0.05), for oviposition in habitats contaminated with mycolactone suggesting a legacy effect.

Does skin surface temperature variation account for Buruli ulcer lesion distribution?

BackgroundBuruli ulcer is a necrotising infection of skin and soft tissue caused by Mycobacterium ulcerans (M. ulcerans). Buruli ulcer most often occurs on limbs, and it is hypothesized this is explained by direct exposure to the environment. However, even on exposed areas Buruli ulcer is not randomly distributed. M. ulcerans prefers an in vitro temperature of 30–33°C and growth is inhibited at higher temperatures. This study investigated whether variations in skin surface temperature distribution in healthy volunteers could partly account for Buruli ulcer lesion distribution.Methodology/Principal findingsIn this observational study, a thermal camera (FLIR E8) was used to measure skin surface temperature at the sternal notch and at 44 predetermined locations on the limbs of 18 human participants. Body locations of high, middle and low Buruli ulcer incidence were identified from existing density maps of lesion distribution. Skin temperature of the three incidence location groups were compared, and differences in age and sex groups were also analysed.We found an inverse relationship between skin temperature and lesion distribution, where high incidence locations were significantly cooler and low incidence locations significantly warmer (Kruskal-Wallis test p<0.0001). Linear mixed effects regression analysis estimated that skin surface temperature accounts for 22.0% of the variance in Buruli ulcer lesion distribution (marginal R-squared = 0.219) in the anterior location group, and 0.6% in the posterior group (marginal R-squared 0.006). Men had warmer upper and lower limbs than females (Mann-Whitney U test p = 0.0003 and p<0.0001 respectively).Conclusions/SignificanceWe have found an inverse relationship between skin temperature and Buruli ulcer lesion distribution, however this association is weak. Additional unknown factors are likely to be involved that explain the majority of the variation in Buruli lesion distribution.

Effect of well drilling on Buruli ulcer incidence in Benin: a case-control, quantitative survey

Buruli ulcer is the third most common mycobacterial disease worldwide. The public health burden of this neglected tropical disease is large, particularly in poor areas of west and central Africa. The development of appropriate preventive strategies is hampered by an incomplete understanding of the epidemiology and transmission of the disease. We investigated the effect of the drilling of wells on Buruli ulcer incidence. In this case-control, quantitative survey, we obtained field data for Buruli ulcer incidence over a 10-year period from a specialised centre that collected data for the Ouémé and Plateau departments in Benin, and data for well drilling from the Ministry of Energy, Water and Mines in Benin. The coordinates of the wells drilled were obtained during site visits. A case-control study was then done to investigate the role of well water use in protecting against Buruli ulcer. We found a strong inverse correlation between the incidence of Buruli ulcer and the number of new wells drilled in the Bonou municipality (r2=0·8818). A case-control study (106 cases and 212 controls) showed that regular use of the water from the wells for washing, bathing, drinking, or cooking was protective against Buruli ulcer (adjusted odds ratio 0·1, 95% CI 0·04-0·44; p=0·0012). This study opens up new possibilities for developing an effective yet affordable policy to fight the disease on a substantial geographical scale. Our study shows that providing access to protected water is an efficient and feasable way to reduce the incidence of Buruli ulcer. Fondation Francaise Raoul Follereau, French National Institute of Health and Medical Research, and Région Pays de Loire.

The association of rainfall and Buruli ulcer in southeastern Australia.

BackgroundBuruli ulcer has been increasing in incidence in southeastern Australia with unclear transmission mechanisms. We aimed to investigate the link between rainfall and case numbers in two endemic areas of the state of Victoria; the Bellarine and Mornington Peninsulas.MethodologyWe created yearly and monthly graphs comparing rainfall with local Buruli ulcer incidence for the period 2004–2016 by endemic region and then considered a range of time lag intervals of 0–24 months to investigate patterns of correlation.ConclusionsOptimal positive correlation for the Bellarine Peninsula occurred with a 12-month prior rainfall lag, however, no significant correlation was observed on the Mornington Peninsula for any time lag. These results provide an update in evidence to further explore transmission mechanisms which may differ between these geographically proximate endemic regions.

Perception and incidence of Buruli ulcer in Ogun State, South West Nigeria: intensive epidemiological survey and public health intervention recommended.

IntroductionBuruli ulcer (BU) is a highly ranked neglected tropical disease (NTD) of global health importance with increasing incidence in sub-Saharan Africa yet there is paucity of information on the epidemiology of BU in Nigeria. Incidentally, highly BU endemic Benin Republic shares proximity with Nigeria. This study was carried out to establish presence of BU and ascertain the level of BU perception among rural populace in Ogun State, south-west Nigeria.MethodsSecondary data (2009-2012) on incidence of BU was collected from a reference hospital. A cross-sectional survey using structured questionnaire administered to rural people and healthcare practitioners was conducted in three purposively chosen Local Government Areas (LGAs) in Ogun State based on unpublished reports of BU presence.ResultsData collected revealed 27 hospital confirmed BU cases between 2009-2012 across four LGAs (Obafemi Owode, Abeokuta North, Yewa North and Yewa South) while 14%(21/150) chronic ulcers (suspected to be BU) were discovered during the cross-sectional survey carried out in Odeda, Yewa South and North LGAs. Healthcare practitioners 63.6% (42/66) and 54.7% (82/150) rural people demonstrated poor level of BU perception respectively.ConclusionThis study provides evidence that BU exists in Ogun State and evaluates the poor perception that the affected rural populace has on the disease. This pilot study presents baseline information on BU in a rural setting in Ogun State South-west Nigeria hence the vital need for prompt public health involvement and further research on the epidemiology of BU.

Seasonal Pattern of Mycobacterium ulcerans, the Causative Agent of Buruli Ulcer, in the Environment in Ghana

This study aimed to contribute to the understanding of Mycobacterium ulcerans (MU) ecology by analysing both clinical and environmental samples collected from ten communities along two major river basins (Offin and Densu) associated with Buruli ulcer (BU) at different seasons. We collected clinical samples from presumptive BU cases and environmental samples from ten communities. Following DNA extraction, clinical samples were confirmed by IS2404 PCR and environmental samples were confirmed by targeting MU-specific genes, IS2404, IS2606 and the ketoreductase (KR) using real-time PCR. Environmental samples were first analysed for IS2404; after which, IS2404-positive samples were multiplexed for the IS2606 and KR gene. Our findings indicate an overall decline in BU incidence along both river basins, although incidence at Densu outweighs that of Offin. Overall, 1600 environmental samples were screened along Densu (434, 27 %) and Offin (1166, 73 %) and MU was detected in 139 (9 %) of the combined samples. The positivity of MU along the Densu River basin was 89/434 (20.5 %), whilst that of the Offin River basin was 50/1166 (4.3 %). The DNA was detected mainly in snails (5/6, 83 %), moss (8/40, 20 %), soil (55/586, 9 %) and vegetation (55/675, 8 %). The proportion of MU positive samples recorded was higher during the months with higher rainfall levels (126/1175, 11 %) than during the dry season months (13/425, 3 %). This study indicates for the first time that there is a seasonal pattern in the presence of MU in the environment, which may be related to recent rainfall or water in the soil.

Characteristics and epidemiological profile of Buruli ulcer in the district of Tiassalé, south Côte d’Ivoire

Buruli ulcer (BU) is a cutaneous infectious disease caused by Mycobacterium ulcerans. It is the third most common mycobacterial disease in the world in the immunocompetent patient and second in Côte d’Ivoire after tuberculosis. This study aimed to assess the characteristics and epidemiological profile of BU in the district of Tiassalé, an important focus of the disease in south Côte d’Ivoire, in order to better direct actions for prevention and control. Retrospective clinical data of BU cases in the period 2005–2010 from all 19 district health centres were collected and linked with geographical and environmental survey data. A total of 1145 cases of BU were recorded between 2005 and 2010 in the district of Tiassalé. Children under the age of 15 years were the most affected (53.0%) with a higher prevalence among males compared to females (54.7% versus 45.3%). Among individuals aged 15–49 years, females had a higher prevalence than males (54.2% versus 45.8%). The villages of Ahondo, Léléblé and Taabo, located in close proximity to the man-made Lake Taabo that was constructed in the late 1970s by damming the Bandama River, and the village of Sokrogbo located downstream of the dam, showed the highest BU rates in the sub-prefecture of Taabo. In the sub-prefecture of Tiassalé, the villages of Affikro, Morokro and N’Zianouan, located near N’Zi River, a tributary of the Bandama River, were the most affected. The distribution of BU is associated with environmental patterns (i.e. distance between village and Lake Taabo or Bandama River and its tributary N’Zi River). Awareness campaigns, coupled with early diagnosis and improved clinical management of BU, have been implemented in the district of Tiassalé and the incidence of BU has declined.

Burden and Historical Trend of Buruli Ulcer Prevalence in Selected Communities along the Offin River of Ghana.

Buruli ulcer (BU) is a neglected tropical skin disease caused by Mycobacterium ulcerans with more than two thirds of the global cases reported in West Africa. A nationwide active BU case search conducted in 1999 identified two health districts along the Offin River as two of the three most endemic districts in Ghana. Based on recent anecdotal accounts that transmission is unstable along the Offin River, we conducted from March to June 2013 an exhaustive household survey and active case search in 13 selected communities within a five-kilometer radius along the Offin River. The overall prevalence of BU was 2.3% among the surveyed population of 20,390 inhabitants and 477 of the total 480 cases detected (99.4%) were historical (healed) cases. By estimating the year of occurrence for each case per community and taking into account available passive surveillance records of health facilities and the District Health Directorate, we observed a general trend of continuous emergence of cases in communities located midstream the Offin River whereas downstream communities showed more sporadic patterns. We monitored the incidence of cases after the survey and recorded a cumulative incidence rate of 0.04% for the 13 communities over a 17-month active surveillance period from August 2013 to December 2014. Our data reveal an overall decline in BU incidence along the Offin River similar to the general decline in BU incidence in recent years reported by the World Health Organization for West Africa.

Socio-Environmental Factors Associated with the Risk of Contracting Buruli Ulcer in Tiassalé, South Côte d'Ivoire: A Case-Control Study.

BackgroundBuruli ulcer (BU) is a cutaneous infectious disease caused by Mycobacterium ulcerans. The exact mode of transmission remains elusive; yet, some studies identified environmental, socio-sanitary, and behavioral risk factors. The purpose of this study was to assess the association of such factors to contracting BU in Tiassalé, south Côte d’Ivoire.MethodologyA case-control study was conducted in 2012. Cases were BU patients diagnosed according to clinical definition put forth by the World Health Organization, readily confirmed by IS2404 polymerase chain reaction (PCR) analysis prior to our study and recruited at one of the health centers of the district. Two controls were matched for each control, by age group (to the nearest 5 years), sex, and living community. Participants were interviewed after providing oral witnessed consent, assessing behavioral, environmental, and socio-sanitary factors.Principal FindingsA total of 51 incident and prevalent cases and 102 controls were enrolled. Sex ratio (male:female) was 0.9. Median age was 25 years (range: 5–70 years). Regular contact with unprotected surface water (adjusted odds ratio (aOR) = 6.5; 95% confidence interval (CI) = 2.1–19.7) and absence of protective equipment during agricultural activities (aOR = 18.5, 95% CI = 5.2–66.7) were identified as the main factors associated with the risk of contracting BU. Etiologic fractions among exposed to both factors were 84.9% and 94.6%, respectively. Good knowledge about the risks that may result in BU (aOR = 0.3, 95% CI = 0.1–0.8) and perception about the disease causes (aOR = 0.1, 95% CI = 0.02–0.3) showed protection against BU with a respective preventive fraction of 70% and 90%.Conclusions/SignificanceMain risk factors identified in this study were the contact with unprotected water bodies through daily activities and the absence of protective equipment during agricultural activities. An effective strategy to reduce the incidence of BU should involve compliance with protective equipment during agricultural activities and avoidance of contact with surface water and community capacity building through training and sensitization.

Environmental transmission of Mycobacterium ulcerans drives dynamics of Buruli ulcer in endemic regions of Cameroon.

Buruli Ulcer is a devastating skin disease caused by the pathogen Mycobacterium ulcerans. Emergence and distribution of Buruli ulcer cases is clearly linked to aquatic ecosystems, but the specific route of transmission of M. ulcerans to humans remains unclear. Relying on the most detailed field data in space and time on M. ulcerans and Buruli ulcer available today, we assess the relative contribution of two potential transmission routes –environmental and water bug transmission– to the dynamics of Buruli ulcer in two endemic regions of Cameroon. The temporal dynamics of Buruli ulcer incidence are explained by estimating rates of different routes of transmission in mathematical models. Independently, we also estimate statistical models of the different transmission pathways on the spatial distribution of Buruli ulcer. The results of these two independent approaches are corroborative and suggest that environmental transmission pathways explain the temporal and spatial patterns of Buruli ulcer in our endemic areas better than the water bug transmission.

Spatial Analysis of Anthropogenic Landscape Disturbance and Buruli Ulcer Disease in Benin.

BackgroundLand use and land cover (LULC) change is one anthropogenic disturbance linked to infectious disease emergence. Current research has focused largely on wildlife and vector-borne zoonotic diseases, neglecting to investigate landscape disturbance and environmental bacterial infections. One example is Buruli ulcer (BU) disease, a necrotizing skin disease caused by the environmental pathogen Mycobacterium ulcerans (MU). Empirical and anecdotal observations have linked BU incidence to landscape disturbance, but potential relationships have not been quantified as they relate to land cover configurations.Methodology/Principal FindingsA landscape ecological approach utilizing Bayesian hierarchical models with spatial random effects was used to test study hypotheses that land cover configurations indicative of anthropogenic disturbance were related to Buruli ulcer (BU) disease in southern Benin, and that a spatial structure existed for drivers of BU case distribution in the region. A final objective was to generate a continuous, risk map across the study region. Results suggested that villages surrounded by naturally shaped, or undisturbed rather than disturbed, wetland patches at a distance within 1200m were at a higher risk for BU, and study outcomes supported the hypothesis that a spatial structure exists for the drivers behind BU risk in the region. The risk surface corresponded to known BU endemicity in Benin and identified moderate risk areas within the boundary of Togo.Conclusions/SignificanceThis study was a first attempt to link land cover configurations representative of anthropogenic disturbances to BU prevalence. Study results identified several significant variables, including the presence of natural wetland areas, warranting future investigations into these factors at additional spatial and temporal scales. A major contribution of this study included the incorporation of a spatial modeling component that predicted BU rates to new locations without strong knowledge of environmental factors contributing to disease distribution.

Seasonal Patterns of Buruli Ulcer Incidence, Central Africa, 2002-2012.

To determine when risk for Buruli ulcer is highest, we examined seasonal patterns in a highly disease-endemic area of Cameroon during 2002–2012. Cases peaked in March, suggesting that risk is highest during the high rainy season. During and after this season, populations should increase protective behaviors, and case detection efforts should be intensified.

Chemistry of natural waters and its relation to Buruli ulcer in Ghana

Abstract Study region Buruli ulcer, an emerging disease caused by Mycobacterium ulcerans, largely affects poor rural populations in tropical countries. The environmental niche that supports this necrotizing bacterium is unclear. Here, water samples were collected from five communities within Ghana in the rainy season in 2011: four in the southern part of Ghana (three disease-endemic communities: Pokukrom, Betenase, and Ayanfuri, and one control: Kedadwen) and one non-endemic community (Nangruma) in the north. Study focus Past studies of Buruli ulcer conclude that water quality is, in some way, closely related to the transmission of this disease. This work serves as a first step to explore links between Buruli ulcer incidence and water quality. More broadly, this research works toward identifying the environmental niche for M. ulcerans, providing characterization of water bodies hazardous to human health in at-risk communities. New hydrological insights Trace metals, thought to aid in the preferential growth of M. ulcerans, are present in higher concentrations in mining pits and stagnant pools than in other tested water bodies. Arsenic in particular could serve as a double threat for BU incidence: it could support the growth of M. ulcerans while suppressing immune systems, making the population more susceptible to disease. Few other differences between endemic and non-endemic communities exist, implying other variables such as human behavior may also control the onset of Buruli ulcer.

Spatio-temporal patterns and landscape-associated risk of Buruli ulcer in Akonolinga, Cameroon.

BackgroundBuruli ulcer (BU) is an extensively damaging skin infection caused by Mycobacterium ulcerans, whose transmission mode is still unknown. The focal distribution of BU and the absence of interpersonal transmission suggest a major role of environmental factors, which remain unidentified. This study provides the first description of the spatio-temporal variations of BU in an endemic African region, in Akonolinga, Cameroon. We quantify landscape-associated risk of BU, and reveal local patterns of endemicity.Methodology/Principal FindingsFrom January 2002 to May 2012, 787 new BU cases were recorded in 154 villages of the district of Akonolinga. Incidence per village ranged from 0 (n = 59 villages) to 10.4 cases/1000 person.years (py); median incidence was 0.4 cases/1,000py. Villages neighbouring the Nyong River flood plain near Akonolinga town were identified as the highest risk zone using the SPODT algorithm. We found a decreasing risk with increasing distance to the Nyong and identified 4 time phases with changes in spatial distribution. We classified the villages into 8 groups according to landscape characteristics using principal component analysis and hierarchical clustering. We estimated the incidence ratio (IR) associated with each landscape using a generalised linear model. BU risk was highest in landscapes with abundant wetlands, especially cultivated ones (IR = 15.7, 95% confidence interval [95%CI] = 15.7[4.2–59.2]), and lowest in reference landscape where primary and secondary forest cover was abundant. In intermediate-risk landscapes, risk decreased with agriculture pressure (from IR[95%CI] = 7.9[2.2–28.8] to 2.0[0.6–6.6]). We identified landscapes where endemicity was stable and landscapes where incidence increased with time.Conclusion/SignificanceOur study on the largest series of BU cases recorded in a single endemic region illustrates the local evolution of BU and identifies the Nyong River as the major driver of BU incidence. Local differences along the river are explained by wetland abundance and human modification of the environment.

Geographic Distribution, Age Pattern and Sites of Lesions in a Cohort of Buruli Ulcer Patients from the Mapé Basin of Cameroon

Buruli ulcer (BU), a neglected tropical disease of the skin, caused by Mycobacterium ulcerans, occurs most frequently in children in West Africa. Risk factors for BU include proximity to slow flowing water, poor wound care and not wearing protective clothing. Man-made alterations of the environment have been suggested to lead to increased BU incidence. M. ulcerans DNA has been detected in the environment, water bugs and recently also in mosquitoes. Despite these findings, the mode of transmission of BU remains poorly understood and both transmission by insects or direct inoculation from contaminated environment have been suggested. Here, we investigated the BU epidemiology in the Mapé basin of Cameroon where the damming of the Mapé River since 1988 is believed to have increased the incidence of BU. Through a house-by-house survey in spring 2010, which also examined the local population for leprosy and yaws, and continued surveillance thereafter, we identified, till June 2012, altogether 88 RT-PCR positive cases of BU. We found that the age adjusted cumulative incidence of BU was highest in young teenagers and in individuals above the age of 50 and that very young children (<5) were underrepresented among cases. BU lesions clustered around the ankles and at the back of the elbows. This pattern neither matches any of the published mosquito biting site patterns, nor the published distribution of small skin injuries in children, where lesions on the knees are much more frequent. The option of multiple modes of transmission should thus be considered. Analyzing the geographic distribution of cases in the Mapé Dam area revealed a closer association with the Mbam River than with the artificial lake.

Application of Area to Point Kriging to Buruli Ulcer Incidence in Ashanti and Brong Ahafo Regions of Ghana

Application of Area to Point Kriging to Buruli Ulcer Incidence in Ashanti and Brong Ahafo Regions of Ghana Buruli ulcer (BU) is the third most common mycobacterium disease after tuberculosis and leprosy. The disease eats through the skin, muscle and bone, leaving victims with disfiguring and debilitating craters. Ghana is the second most endemic country globally, after Cote d’Ivoire with over 1,048 cases with the most endemic regions being the Ashanti, Greater Accra, Central and the Brong Ahafo. The goal of the paper is to use Area to Point Kriging (ATP) method to model the spatial distribution of Buruli ulcer incidence in the Ashanti and Brong Ahafo Regions of Ghana.

Climate and landscape factors associated with Buruli ulcer incidence in Victoria, Australia.

BackgroundBuruli ulcer (BU), caused by Mycobacterium ulcerans (M. ulcerans), is a necrotizing skin disease found in more than 30 countries worldwide. BU incidence is highest in West Africa; however, cases have substantially increased in coastal regions of southern Australia over the past 30 years. Although the mode of transmission remains uncertain, the spatial pattern of BU emergence in recent years seems to suggest that there is an environmental niche for M. ulcerans and BU prevalence.Methodology/Principal FindingsNetwork analysis was applied to BU cases in Victoria, Australia, from 1981–2008. Results revealed a non-random spatio-temporal pattern at the regional scale as well as a stable and efficient BU disease network, indicating that deterministic factors influence the occurrence of this disease. Monthly BU incidence reported by locality was analyzed with landscape and climate data using a multilevel Poisson regression approach. The results suggest the highest BU risk areas occur at low elevations with forested land cover, similar to previous studies of BU risk in West Africa. Additionally, climate conditions as far as 1.5 years in advance appear to impact disease incidence. Warmer and wetter conditions 18–19 months prior to case emergence, followed by a dry period approximately 5 months prior to case emergence seem to favor the occurrence of BU.Conclusions/SignificanceThe BU network structure in Victoria, Australia, suggests external environmental factors favor M. ulcerans transmission and, therefore, BU incidence. A unique combination of environmental conditions, including land cover type, temperature and a wet-dry sequence, may produce habitat characteristics that support M. ulcerans transmission and BU prevalence. These findings imply that future BU research efforts on transmission mechanisms should focus on potential vectors/reservoirs found in those environmental niches. Further, this study is the first to quantitatively estimate environmental lag times associated with BU outbreaks, providing insights for future transmission investigations.

L’ulcère de Buruli : hypothèses relatives au mode de transmission de Mycobacterium ulcerans

The incidence of Buruli ulcer, caused by Mycobacterium ulcerans, has been increasingly rapidly over the past thirty years, particularly in Africa. These extensive necrotic lesions are due to mycolactone, a toxin produced by the bacterium. The mode of Mycobacterium ulcerans transmission is still controversial, and several insect species have been incriminated. Several infected mosquito species have been identified in Australia, while predatory water bugs, particularly belostomatids and naucorids, have been implicated in Africa. Indeed, the bacterium has been detected in these insects' salivary glands, and experimental transmission to mice has been demonstrated, raising the possibility of human transmission by water bug bites. Interestingly, individuals highly exposed to water bug bites tend to be less often infected, indicating that frequent bites by non infected bugs might have a protective effect. Insect-borne transmission would be a minor route of transmission compared to direct transmission via skin trauma.