Therapeutic trials in visceral, dermal, and cutaneous leishmaniasis: Real-world applications and outcomes

The story of antileishmanial drug development has unfolded over a century and continues to evolve. The initial drug development was restricted to and largely guided by case studies. Initial randomized studies were undertaken in Eastern Africa in the 1980s, and since then controlled evaluation of drugs has been undertaken across areas of different endemicities. This chapter presents a succinct historical evolution of drug development and presents the current state of therapeutic interventions for visceral leishmaniasis (VL), post-kala-azar dermal leishmaniasis (PKDL), and cutaneous leishmaniasis (CL). In particular, we discuss the existing evidence derived from recently undertaken large-scale systematic reviews and meta-analyses on VL and PKDL. For CL, we summarize the challenges that continue to pose difficulties for synthesis of evidence, owing to the methodological heterogeneities in trial design and conduct. We discuss opportunities in using real-world data derived from observational databases and national surveillance systems that can fill the evidence vacuum for patient groups frequently excluded in clinical trials, to inform policy and research. Finally, the chapter identifies future opportunities for VL therapeutic advancements, and advocates for pragmatic trials to bridge the gap between controlled research and routine clinical practice.