Secondary bacterial infection in Buruli ulcer

Abstract
Buruli ulcer (BU) is a chronic debilitating disease of the skin and soft tissues caused by Mycobacterium ulcerans. It is one of the 17 neglected tropical diseases according to the World Health Organization and has been reported in over 30 countries with tropical and sub-tropical conditions globally. M. ulcerans is traditionally considered as an environmental pathogen and even though BU was discovered over half a century ago, the environmental reservoir and exact mode of transmission of this pathogen remain obscure. This makes it challenging to formulate strategies for its prevention. As such, control strategies geared towards the early detection and treatment of cases are vital to minimize morbidity, disability and the socio-economic burden associated with the disease. The introduction of antibiotic therapy for treatment in 2004 to replace surgery as first-line therapy has brought about an improvement in the management of the disease. However, despite reported successful outcomes with the antibiotic treatment, the healing process is still characterized by long hospitalizations as a result of delayed wound closure.
In this thesis, we explored the factors which could contribute to the observed delayed wound healing in two BU treatment centers in Ghana; the Ga-West Municipal Hospital and the Obom Health Center. Through a combination of clinical, microbiological and histopathological analysis, we identified secondary infection of BU lesions by other bacteria as a major cause of delayed healing. Through quantitative microbiological studies, we analysed the evolution of the bacterial burden and identified increased loads of bacteria post treatment which could negatively impact on the healing potential of the wounds. Furthermore, we explored co-infection with Human immunodeficiency virus (HIV) in the Ga-West Municipal Hospital as a challenge to the management of BU and described challenges associated with the management of this co-infection. Studying the isolated bacterial species through phenotypic, molecular and whole genome approaches helped to identify health-care associated transmission through health workers and equipment as well as self transmission as potential sources of wound infection within the health centers. With these results, we made recommendations for the improvement of wound management in the health centers and made a case for the need for wound management guidelines which were absent in the health centers. We followed this up with the development of local guidelines for wound care and the implementation of several interventions in the health centers. We also identified antibiotic resistance as an increasing problem and described in detail through whole genome sequencing, a recently emerged and rapidly spreading clone of community acquired methicillin resistant Staphylococcus aureus with sequence type 88 in Ghana which has the potential to become a serious public health threat with implications for healthcare. This alarming result therefore calls for the urgent establishment of a surveillance system to monitor the use and distribution of antibiotics in Ghana and the emergence of antibiotic resistant pathogens.