Global and local environmental changes as drivers of Buruli ulcer emergence

Abstract

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.

Figure 1

Two types of lesions caused by Buruli ulcer (BU). (A) An ulceration of the knee; (B) A plaque on the arm. These photographs were provided by Professor Pierre Couppié (Cayenne Hospital), who has an ethical agreement with the patients.

Figure 2

Global distribution of Buruli ulcer (BU) cases, from 2002 to 2015. The map displays the total number of BU cases reported to the World Health Organization in 2016 on a red color scale. This information was completed for French Guiana by collaborators, on the basis of hospital records (Professor Pierre Couppié, personal communication). The map was created using ArcMap v.10.2.2.

Figure 3

Distribution of Mycobacterium ulcerans (MU) DNA across the entire aquatic food web. Organisms assimilate carbon (C) and nitrogen (N) stable isotopes by feeding, and analysis of their stable isotope signatures thus allows for the study of trophic food webs. The direction of the arrow and the pictures of some MU hosts illustrate the food web, from low to high trophic levels: aquatic plants (Araceae), Baetidae, Belostomatidae, Nepidae and fish (Cichlidae). The average δ¹³C and δ¹⁵N signatures were obtained from stable isotope analyses of each taxon of the aquatic environment sampled from 17 sites in French Guiana (South America) and tested positive by qPCR for IS2404 and KR genetic markers. The amplification of these markers confirms the presence and abundance of MU. For each taxon, the average bacterial load (for example, number of bacteria per mg of organism) is represented by the size of the red circles on the basis of transformed data using the square root mean number of bacteria (detailed information in Supplementary Table S2). Adapted from Morris et al.

Figure 4

Schematic representation of the links between land-use changes and climatic patterns favoring the emergence of Mycobacterium ulcerans (MU) in the environment. Red dots represent the distribution of MU in the environment (panels 1, 2 and 3) as well as among host carrier species communities (panel 4). The top panel shows a pristine ecosystem with MU in low abundance within the aquatic ecosystem. However, in the second panel, deforestation and climatic events (for example, heavy rain) result in intensive flooding and redistribution of MU in the ecosystem. On the left riverbank, the forest has been cut down, whereas on the right, the ecosystem remains pristine.The third panel shows water receding, thus allowing for the formation of small oxbows, which (when the trees have been cut down) are subjected to higher temperatures, higher biofilm development and lower pH and oxygen levels (conditions that are prone to cause the bacterial proliferation). MU is not established in the shaded oxbow. When associated with an increase in contact rates with humans due to a change in land use, the infectious risk of BU becomes greater. The bacterial distribution in the environment and within a high diversity of hosts suggests multiple routes of transmission to humans. The position of aquatic hosts in the water column illustrates their trophic level, from low trophic level organisms (for example, grazing invertebrates) to higher trophic level organisms (for example, fish). Aquatic organisms of a low trophic level generally present greater bacterial loads compared with organisms of a higher trophic level; zero dots represent the absence of MU, and four dots represent a high MU load. Illustration by Emily S. Damstra.