Buruli Ulcer Research at MSU

The overall goal of the proposed study is to examine, build and test predictive models that define the relationships between landscape change and ecological disturbance in freshwater food webs and the ecological distribution of Mycobacterium ulcerans in water bodies along a gradient of human infection incidence in Ghana, Africa This study will be the first of its kind to examine these relationships, information that will make a substantial contribution to understanding broader patterns of human environmental impacts, ecologically related changes, disease emergence, transmission, prevention and control.

The specific aim of the proposed study is to determine the possible role(s) of aquatic invertebrates as potential reservoirs of Mycobacterium ulcerans within and among aquatic habitats in Ghana, Africa. Because the DNA of M. ulcerans has been detected in several aquatic invertebrates, a food web-based hypothesis of potential aquatic invertebrate reservoirs of this bacterium has been proposed. Based upon this hypothesis and recent laboratory studies demonstrating that at least one aquatic insect is capable of transmitting this mycobacterium to mice, we propose to determine the extent of M. uclerans within the aquatic invertebrate trophic community structure of standing waterbodies (e.g., swamps, slow moving rivers, and wetlands) in BU endemic and non-endemic areas. We will take an innovative, systematic, and hierarchical approach to identifying the trophic relationships and links of potential aquatic invertebrate reservoirs, and how they might facilitate the movement of M. ulcerans in the aquatic environment. The hierarchical approach is based upon the following spatial scales: regional, landscape, habitat, and community. We also will use GIS to assess immediate landscape features (e.g., deforestation, agriculture, population density) potentially influencing the ecological distribution and trophic structure of aquatic invertebrate taxa of waterbodies in endemic and non-endemic regions. The project objectives and associated hypotheses are addressed within the following spatially explicit hierarchical framework:

Regional Scale

Objective #1: GIS Mapping and Site Selection - We propose to map landscape features and biophysical attributes associated with known occurrences of Buruli Ulcer. We will use GIS to overlay high resolution data coverages of landscape uses (e.g., agriculture, urban, forests, lakes, and streams) and Buruli Ulcer prevalence to stratify regions with waterbodies associated with Buruli Ulcer outbreaks from those that do not, and to statistically determine waterbody trophic condition relationships with M. ulcerans occurrence. The mapping will be used to select appropriate study sites for focused limnological studies

Hypothesis: We predict that regions with higher rates of Buruli Ulcer disease will be associated with landscape features such as deforestation and human created aquatic impoundments, each known to be associated with the habitats and distribution of potential aquatic invertebrate reservoirs of M. ulcerans.

Landscape Scale

Objective #2: Limnological Studies - We will conduct intensive limnological studies of the selected waterbodies to identify abiotic and biotic relationships that may interact to influence the extent of M. ulcerans in the environment, whether through invertebrate feeding interactions (trophic links) or abiotic landscape constraints (e.g., aquatic vegetation coverage).

Hypothesis: We predict that specific limnological variables (e.g. water clarity, oxygen conditions, vegetation types) will determine the density and distribution of aquatic invertebrates that potentially harbor M. ulcerans. The direction of these constraints will occur from both bottom-up (e.g., biofilm biomass) and top-down (e.g., fish) mechanisms.

Habitat Scale

Objective #3: Trophic Structure (Intra-waterbody Transmission) - The biotic component of the limnological studies will be used to identify the trophic structure and possible feeding linkages of each waterbody. The trophic structure will include an inventory of the macrophytes, invertebrates, and fish and their functional feeding group classifications and associations.

Hypothesis: We predict that the trophic relationships among aquatic invertebrates will help to identify the ecological distribution and potential modes of intra-waterbody transmission of M. ulcerans.

Community Scale

Objective #4: PCR Detection of M. ulcerans - The extent of M. ulcerans in the environment and among aquatic invertebrates, fish and other biotic components (plants, biofilm) will be determined for individual taxa representing different trophic groups using PCR assays (using primers specific for M. ulcerans).

Hypothesis: We predict that the position of particular invertebrates within the food web (their functional feeding group designation) will determine the probability of harboring M. ulcerans.

BU 12

A flow diagram showing the scale of measurement and linkages of potential research interest for determining ecological connections important to BU incidence and future control effort.