Extending the durability of cultivar resistance by limiting epidemic growth rates.

Cultivar resistance is an essential part of disease control programmes in many agricultural systems. The use of resistant cultivars applies a selection pressure on pathogen populations for the evolution of virulence, resulting in loss of disease control. Various techniques for the deployment of host resistance genes have been proposed to reduce the selection for virulence, but these are often difficult to apply in practice. We present a general technique to maintain the effectiveness of cultivar resistance. Derived from classical population genetics theory; any factor that reduces the population growth rates of both the virulent and avirulent strains will reduce selection. We model the specific example of fungicide application to reduce the growth rates of virulent and avirulent strains of a pathogen, demonstrating that appropriate use of fungicides reduces selection for virulence, prolonging cultivar resistance. This specific example of chemical control illustrates a general principle for the development of techniques to manage the evolution of virulence by slowing epidemic growth rates.

Global and local environmental changes as drivers of Buruli ulcer emergence.

Many emerging infectious diseases are caused by generalist pathogens that infect and transmit via multiple host species with multiple dissemination routes, thus confounding the understanding of pathogen transmission pathways from wildlife reservoirs to humans. The emergence of these pathogens in human populations has frequently been associated with global changes, such as socio-economic, climate or biodiversity modifications, by allowing generalist pathogens to invade and persist in new ecological niches, infect new host species, and thus change the nature of transmission pathways. Using the case of Buruli ulcer disease, we review how land-use changes, climatic patterns and biodiversity alterations contribute to disease emergence in many parts of the world. Here we clearly show that Mycobacterium ulcerans is an environmental pathogen characterized by multi-host transmission dynamics and that its infectious pathways to humans rely on the local effects of global environmental changes. We show that the interplay between habitat changes (for example, deforestation and agricultural land-use changes) and climatic patterns (for example, rainfall events), applied in a local context, can lead to abiotic environmental changes and functional changes in local biodiversity that favor the pathogen's prevalence in the environment and may explain disease emergence.

Deforestation-driven food-web collapse linked to emerging tropical infectious disease, Mycobacterium ulcerans.

Generalist microorganisms are the agents of many emerging infectious diseases (EIDs), but their natural life cycles are difficult to predict due to the multiplicity of potential hosts and environmental reservoirs. Among 250 known human EIDs, many have been traced to tropical rain forests and specifically freshwater aquatic systems, which act as an interface between microbe-rich sediments or substrates and terrestrial habitats. Along with the rapid urbanization of developing countries, population encroachment, deforestation, and land-use modifications are expected to increase the risk of EID outbreaks. We show that the freshwater food-web collapse driven by land-use change has a nonlinear effect on the abundance of preferential hosts of a generalist bacterial pathogen, Mycobacterium ulcerans. This leads to an increase of the pathogen within systems at certain levels of environmental disturbance. The complex link between aquatic, terrestrial, and EID processes highlights the potential importance of species community composition and structure and species life history traits in disease risk estimation and mapping. Mechanisms such as the one shown here are also central in predicting how human-induced environmental change, for example, deforestation and changes in land use, may drive emergence.

A Field Study in Benin to Investigate the Role of Mosquitoes and Other Flying Insects in the Ecology of Mycobacterium ulcerans.

BACKGROUND: Buruli ulcer, the third mycobacterial disease after tuberculosis and leprosy, is caused by the environmental mycobacterium M. ulcerans. There is at present no clear understanding of the exact mode(s) of transmission of M. ulcerans. Populations affected by Buruli ulcer are those living close to humid and swampy zones. The disease is associated with the creation or the extension of swampy areas, such as construction of dams or lakes for the development of agriculture. Currently, it is supposed that insects (water bugs and mosquitoes) are host and vector of M. ulcerans. The role of water bugs was clearly demonstrated by several experimental and environmental studies. However, no definitive conclusion can yet be drawn concerning the precise importance of this route of transmission. Concerning the mosquitoes, DNA was detected only in mosquitoes collected in Australia, and their role as host/vector was never studied by experimental approaches. Surprisingly, no specific study was conducted in Africa. In this context, the objective of this study was to investigate the role of mosquitoes (larvae and adults) and other flying insects in ecology of M. ulcerans. This study was conducted in a highly endemic area of Benin. METHODOLOGY/PRINCIPAL FINDINGS: Mosquitoes (adults and larvae) were collected over one year, in Buruli ulcer endemic in Benin. In parallel, to monitor the presence of M. ulcerans in environment, aquatic insects were sampled. QPCR was used to detected M. ulcerans DNA. DNA of M. ulcerans was detected in around 8.7% of aquatic insects but never in mosquitoes (larvae or adults) or in other flying insects. CONCLUSION/SIGNIFICANCE: This study suggested that the mosquitoes don't play a pivotal role in the ecology and transmission of M. ulcerans in the studied endemic areas. However, the role of mosquitoes cannot be excluded and, we can reasonably suppose that several routes of transmission of M. ulcerans are possible through the world.

Buruli ulcer in South Western Nigeria: a retrospective cohort study of patients treated in Benin.

Nigeria is known to be endemic to Buruli ulcer, but epidemiological data are remarkably rare. Here, we present a large cohort of 127 PCR-confirmed M. ulcerans infection patients coming from Nigeria and treated in a neighbouring country, Benin. Severe lesions and delay of consultation are factors that should encourage establishment of a treatment centre in South Western Nigeria.

Topography and land cover of watersheds predicts the distribution of the environmental pathogen Mycobacterium ulcerans in aquatic insects.

BACKGROUND: An understanding of the factors driving the distribution of pathogens is useful in preventing disease. Often we achieve this understanding at a local microhabitat scale; however the larger scale processes are often neglected. This can result in misleading inferences about the distribution of the pathogen, inhibiting our ability to manage the disease. One such disease is Buruli ulcer, an emerging neglected tropical disease afflicting many thousands in Africa, caused by the environmental pathogen Mycobacterium ulcerans. Herein, we aim to describe the larger scale landscape process describing the distribution of M. ulcerans. METHODOLOGY: Following extensive sampling of the community of aquatic macroinvertebrates in Cameroon, we select the 5 dominant insect Orders, and conduct an ecological niche model to describe how the distribution of M. ulcerans positive insects changes according to land cover and topography. We then explore the generalizability of the results by testing them against an independent dataset collected in a second endemic region, French Guiana. PRINCIPAL FINDINGS: We find that the distribution of the bacterium in Cameroon is accurately described by the land cover and topography of the watershed, that there are notable seasonal differences in distribution, and that the Cameroon model does not predict the distribution of M. ulcerans in French Guiana. CONCLUSIONS/SIGNIFICANCE: Future studies of M. ulcerans would benefit from consideration of local structure of the local stream network in future sampling, and further work is needed on the reasons for notable differences in the distribution of this species from one region to another. This work represents a first step in the identification of large-scale environmental drivers of this species, for the purposes of disease risk mapping.

Ecological niche modelling of Hemipteran insects in Cameroon; the paradox of a vector-borne transmission for Mycobacterium ulcerans, the causative agent of Buruli ulcer.

BACKGROUND: The mode of transmission of the emerging neglected disease Buruli ulcer is unknown. Several potential transmission pathways have been proposed, such as amoebae, or transmission through food webs. Several lines of evidence have suggested that biting aquatic insects, Naucoridae and Belostomatidae, may act as vectors, however this proposal remains controversial. MATERIALS AND METHODS: Herein, based on sampling in Cameroon, we construct an ecological niche model of these insects to describe their spatial distribution. We predict their distribution across West Africa, describe important environmental drivers of their abundance, and examine the correlation between their abundance and Buruli ulcer prevalence in the context of the Bradford-Hill guidelines. RESULTS: We find a significant positive correlation between the abundance of the insects and the prevalence of Buruli ulcer. This correlation changes in space and time, it is significant in one Camerounese study region in (Akonolinga) and not other (Bankim). We discuss notable environmental differences between these regions. CONCLUSION: We interpret the presence of, and change in, this correlation as evidence (though not proof) that these insects may be locally important in the environmental persistence, or transmission, of Mycobacterium. ulcerans. This is consistent with the idea of M. ulcerans as a pathogen transmitted by multiple modes of infection, the importance of any one pathway changing from region to region, depending on the local environmental conditions.

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

BACKGROUND: Buruli 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 FINDINGS: From 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/1,000 py. 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/SIGNIFICANCE: Our 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.