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Buruli Ulcer

Buruli ulcer Disease (BU) is found in tropical and subtropical regions around the world, with cases reported in at least 33 countries from Africa, Australia, Asia, Latin America and the Pacific (1,2). Incidence has been highest in sub-Saharan Africa, with increasing prevalence in nations such as Ghana, Benin and Côte d'Ivoire (3). In some West African countries, BU is the second most common mycobacterial disease after tuberculosis (4).

Infection usually begins as a nodule on extremities and progresses to an open ulcer characterized by extensive necrosis. Mycobacterium ulcerans produces a polyketide toxin, called mycolactone, that is immunosuppressive and cytotoxic leading to ulcerations and necrosis (5,6). Infections are often extensive, causing severe deformities and sometimes amputation of limbs (7). Infection occurs in all age groups but children 7-15 years of age are predominately affected, followed by adults above the age of 50 years (4, 7, 8). Additional clinical aspects of BU are found in several reviews (1,2,6,9-12).

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Buruli ulcer has severe and lasting morbidity in developing nations of West Africa. Fear of surgery, long distances to treatment facilities, and socioeconomic factors contribute to the rural poor being most negatively affected by BU (13,14). Patients often require extensive surgery and hospital stays, creating economic challenges for families. The WHO reported in Ghana the cost of treating a pre-ulcerative nodule in a patient was nearly 16% of the average annual family income; the cost of treating a patient requiring amputation was 89%; and the average cost of treating a patient in 1994-1996 exceeded the per capita government spending on health (8).

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Ecological mechanisms of BU emergence were historically inferred from observations and epidemiological surveys (1,2,15). Most recently, field research in highly endemic foci of Australia and West Africa have provided quantitative information on environmental reservoirs and potential vectors important to disease transmission (16-26), including laboratory research demonstrating that a puncture is needed for infection in mammalian model.

However, much remains unknown regarding the transmission, ecology and environmental distribution of M. ulcerans. This is due to several issues including technical difficulties culturing, identifying and quantifying M. ulcerans from the environment; potential geographic differences in ecological reservoirs/vectors (27-30); unknown time lags regarding human and environmental incubation and reservoir/vector dynamics (31). These areas of inquiry have inspired many studies on BU, but few have been based in ecological theory.

Our current work takes an eco-evo approach to understanding how M. ulcerans functions, persists and disperses in the natural environment, bringing it closer to human hosts.

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References

  1. Merritt, R.W., Benbow, M.E., and Small, P.L.C. (2005). Unraveling an Emerging Disease Associated with Disturbed Aquatic Environments: The Case of Buruli Ulcer. Frontiers in Ecology and the Environment 3(6), 323-331.

  2. Merritt, R.W., Walker, E.D., Small, P.L., Wallace, J.R., Johnson, P.D., Benbow, M.E., et al. (2010). Ecology and transmission of Buruli ulcer disease: a systematic review. PLoS Negl Trop Dis 4(12), e911.

  3. van der Werf, T.S., Stienstra, Y., Johnson, C., Phillips, R., Adjei, O., Fleischer, B., et al. (2005). Mycobacterium ulcerans disease. Bulletin of the World Health Organization 83, 785-791.

  4. Debacker, M., Aguiar, J., Steunou, C., Zinsou, C., Meyers, W.M., Scott, J.T., et al. (2004). Mycobacterium ulcerans disease: role of age and gender in incidence and morbidity. Trop Med Int Health 9(12), 1297-1304.

  5. George, K.M., Welty, D., Pascopella, L., and Small, P.L.C. (2000). The Mycobacterium ulcerans mycolactone causes apoptosis in tissue culture cells and in guinea pig ulcers. Infection and Immunity 68, 877-883.

  6. Johnson, P.D.R., Stinear, T.P., Small, P.L.C., Pluschke, G., Merritt, R.W., Portaels, F., et al. (2005). Buruli ulcer (M. ulcerans Infection): new insights, new hope for disease control. PLoS Med 2(4), e108.

  7. WHO (2000). "Buruli ulcer - diagnosis of Mycobacterium ulcerans disease". (Geneva: World Health Organization, Geneva, Switzerland).

  8. WHO (2008). "Buruli ulcer: progress report, 2004-2008," in Weekly epidemiological record, ed. WHO. (Geneva, Switzerland: World Health Organization), 83, 145-156.

  9. Thangaraj, H.S., Phillips, R.O., Evans, M.R.W., and Wansbrough-Jones, M.H. (2003). Emerging aspects of Buruli ulcer. Expert Rev. Anti-infect. Ther. 1(2), 217-222.

  10. Duker, A.A., Portaels, F., and Hale, M. (2006). Pathways of Mycobacterium ulcerans infection: A review. Environment International 32(4), 567-573.

  11. Benbow, M.E., Hall, B.S., Mosi, L., Roberts, S., Simmonds, R., and Williamson-Jordan, H.R. (2016). "Mycobacterium ulcerans and Buruli ulcer," in Human Emerging and Re-Emerging Infections: Bacterial & Mycotic Infections, ed. S.K. Singh. (New Jersey: John Wiley & Sons, Ltd), 841-861.

  12. Benbow, M.E., Simmonds, R., RW Merritt, R.W., and Jordan, H.R. (2017). "Buruli ulcer: case study of a neglected tropical disease," in Advances in Environmental Microbiolog: Modeling the transmission and prevention of infectious disease, ed. C.J. Hurst. (Cham, Switzerland: Springer International Publishing), 105-149.

  13. Asiedu, K., and Etuaful, S. (1998). Socioeconmoic implications of Buruli ulcer in Ghana: a three-year review. Trans. R. Soc. Trop. Med. & Hyg. 59, 1015-1022.

  14. Raghunathan, P.L., Whitney, E.A.S., Asamoa, K., Stienstra, Y., Taylor, T.H., Jr., Amofah, G.K., et al. (2005). Risk factors for Buruli Ulcer disease (Mycobacterium ulcerans Infection): results from a case-control study in Ghana. Clinical Infectious Diseases 40, 1445-1453.

  15. Jacobsen, K.H., and Padgett, J.J. (2010). Risk factors for Mycobacterium ulcerans infection. International Journal of Infectious Diseases 14(8), e677-e681.

  16. Johnson, P.D.R., Azuolas, J., Lavender, C.J., Wishart, E., Stinear, T.P., Hayman, J., et al. (2007). Mycobacterium ulcerans in mosquitoes captured during outbreak of Buruli ulcer, Southeastern Australia. Emerg Infect Dis 13(11), 1653-1660.

  17. Benbow, M., Williamson, H., Kimbirauskus, R., McIntosh, M., Kolar, R., Quaye, C., et al. (2008). Aquatic invertebrates as unlikely vectors of Buruli ulcer disease. Emerg Infect Dis . http://www.cdc.gov/EID/content/14/8/1247.htm.

  18. Williamson, H.R., Benbow, M.E., Nguyen, K.D., Beachboard, D.C., Kimbirauskas, R.K., McIntosh, M.D., et al. (2008). Distribution of Mycobacterium ulcerans in Buruli ulcer endemic and non-endemic aquatic sites in Ghana. PLoS Neglected Tropical Diseases 2(3), e205.

  19. Fyfe, J.A.M., Lavender, C.J., Handasyde, K.A., Legione, A.R., O'Brien, C.R., Stinear, T.P., et al. (2010). A major role for mammals in the ecology of Mycobacterium ulcerans. Plos Neglected Tropical Disease 4(8), e791.

  20. Williamson, H.R., Benbow, M.E., Campbell, L.P., Johnson, C.R., Ghislain, S., Barogui, Y., et al. (2012). Detection of Mycobacterium ulcerans in the environment predicts prevalence of Buruli ulcer in Benin. PLoS Negl Trop Dis 6(1), 9.

  21. Benbow, M., Kimbirauskus, R., McIntosh, M., Williamson, H., Quaye, C., Boakye, D., et al. (2013). Aquatic macroinvertebrate assemblages of Ghana, West Africa: understanding the ecology of Buruli ulcer disease. EcoHealth DOI: 10.1007/s10393-013-0886-7.

  22. Roche, B., Benbow, M.E., Merritt, R.W., Kimbirauskas, R.K., McIntosh, M.D., Small, P.L.C., et al. (2013). Identifying Achilles' heel of multi-host pathogens: the concept of keystone "host" species illustrated by Mycobacterium ulcerans transmission. Environmental Research Letters 8(4):045009.

  23. McIntosh, M., Williamson, H., Benbow, M.E., Kimbirauskas, R., Quaye, C., Boakye, D., et al. (2014). Associations Between Mycobacterium ulcerans and Aquatic Plant Communities of West Africa: Implications for Buruli Ulcer Disease. EcoHealth 11(2), 184-196.

  24. Morris, A., Guégan, J.-F., Benbow, M.E., Williamson, H., Small, P.L., Quaye, C., et al. (2016). Functional Diversity as a New Framework for Understanding the Ecology of an Emerging Generalist Pathogen. EcoHealth 13(3), 570-581

  25. Garchitorena, A., Ngonghala, C.N., Texier, G., Landier, J., Eyangoh, S., Bonds, M.H., et al. (2015). Environmental transmission of Mycobacterium ulcerans drives dynamics of Buruli ulcer in endemic regions of Cameroon. Scientific Reports 5.

  26. Wallace, J.R., Mangas, K.M., Porter, J.L., Marcsisin, R., Pidot, S.J., Howden, B., et al. (2017). Mycobacterium ulcerans low infectious dose and mechanical transmission support insect bites and puncturing injuries in the spread of Buruli ulcer. PLoS Neglected Tropical Diseases 11(4), e0005553.

  27. Wagner, T., Benbow, M.E., Brenden, T., Qi, J., and Johnson, R.C. (2008a). Buruli ulcer disease prevalence in Benin, West Africa: associations with land use/cover and the identification of disease clusters. International Journal of Health Geographics 7(1), 25.

  28. Wagner, T., Benbow, M.E., Burns, M., Johnson, R.C., Merritt, R., Qi, J., et al. (2008b). A Landscape-based Model for Predicting Mycobacterium ulcerans Infection (Buruli Ulcer Disease) Presence in Benin, West Africa. EcoHealth 5(1), 69-79.

  29. van Ravensway, J., Eric Benbow, M.E., Tsonis, A.A., Pierce, S.J., Campbell, L.P., Fyfe, J.A.M., et al. (2012). Climate and Landscape Factors Associated with Buruli ulcer Incidence in Victoria, Australia. PLoS ONE 7(12), e51074.

  30. Vandelannoote, K., Meehan, C.J., Eddyani, M., Affolabi, D., Phanzu, D.M., Eyangoh, S., et al. (2017). Multiple introductions and recent spread of the emerging human pathogen Mycobacterium ulcerans across Africa. Genome Biology Evolution 9(3), 414-426.

  31. Marion, E., Eyangoh, S., Yeramian, E., Doannio, J., Landier, J., Aubry, J., et al. (2010). Seasonal and regional dynamics of M. ulcerans transmission in environmental context: deciphering the role of water bugs as hosts and vectors. Plos Neglected Tropical Diseases 4(7), e731.