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This chapter explores the role of indigenous knowledge system (IKS) in the development of informal entrepreneurial models in Africa. This was undertaken through a discussion of the production processes and the marketing platforms used in producing and distributing mpesu (a traditional medicine used for sex enhancement and reproductive healthcare) by Traditional Healthcare Practitioners (THPs) in the Vhembe District of South Africa, and Beitbridge areas of Zimbabwe. The argument is that drawing on Vhavenda IKS-based strategies, entrepreneurs involved in the healthcare product have managed to develop context-appropriate and innovative strategies for marketing mpesu. However, while this model may appear unorthodox, it has helped sustain the appetite and demand for the product. It has also, despite its imperfections, provided economic safety-net for local entrepreneurs.

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