Buruli ulcer: Case study of a neglected tropical disease.

Neglected tropical diseases affect almost all human communities in rural areas of mostly developing nations. They have staggering negative effects on human health and local, regional, and national economies through mortality and morbidity. These diseases are neglected in many large-scale disease management and control programs and therefore do not recieve the research and funding attention of diseases with higher pharmaceutical potential. One such disease that epitomozies this situation is Buruli ulcer disease, also known as Mycobacterium ulcerans infection. This necrotizing skin disease results in severe and lasting morbidity that primarily affects children in rural regions of Africa and other tropical and subtropical regions. It is caused by a mycobacterium related to other pathogens that are the agents for two other diseases, leprosy and tuberculosis; however, this pathogen secretes myolactone which is a cytotoxic molecule that is both necrotizing and immunodepressive and is unique within its phylogeny. As a neglected tropical disease, research and funding has generally been sporadic and diffuse among countries and agencies, limiting scientific gains in better understanding some basic disease system tenants such as the mode of transmission and where the pathogen grows and replicates in the environment. These limitations compounded with the fact that it focally affects rural and poor populations have made the control of Buruli ulcer disease challenging. Further, disease emergence and reemergence is thought to be associated with landscape modifications such as deforestation, dam construction, farming, and mining, coupling this disease with degraded environmental conditions that may faciliate either the emergence or sustainability of other water-related diseases of the rural poor. This chapter generally reviews Buruli ulcer disease within the context of neglected tropical diseases in a way that integrates the research that occurs at the molecular and cellular level of pathogen and host investigation with broader ecosystem factors that include other biological interactions (e.g., food webs) considered to be important to elucidating transmission of the pathogen, all of which must be assessed in combination to achieve successful future disease management activities.