Chapter 6: Drugs for Kinetoplastid Diseases – Current Situation and Challenges

The current situation and challenges for treatments for the three human diseases caused by kinetoplastid parasites, leishmaniasis, Chagas disease and human African trypanosomiasis (HAT), are very different. New formulations, therapeutic switching and the potential for combinations of the established drugs, have significantly improved the opportunities for the treatment of visceral leishmaniasis (VL), especially in the Indian subcontinent. However, for HAT, Chagas disease and cutaneous leishmaniases there has been limited progress over the past decade. For the treatment of HAT the only advances over the past two decades have been the demonstrations that an eflornithine/nifurtimox co-administration and a new regime for melarsoprol can shorten treatment duration. Future hopes for the treatment of the CNS stage of this disease are based upon a nitroimidazole, fexinidazole, currently in Phase I clinical studies. A diamidine derivative and an oxoborazole are in the later stages of pre-clinical studies. For Chagas disease, some anti-fungal triazoles, which showed potential in experimental studies over a decade ago, are now moving into clinical studies. Treatments for early chronic and indeterminate infections have been given priority and clinical studies with benznidazole, a drug only previously recommended for acute stage treatment, are in progress. Cutaneous leishmaniasis remains the most neglected disease with little promised.