Neglected Diseases
Kinetoplastid infections include three diseases: leishmaniasis; Chagas’ disease (also known as American trypanosomiasis); and sleeping sickness (human African trypanosomiasis).
Leishmaniasis – caused by Leishmania parasites and spread by phlebotomine sand flies – has three forms: visceral (the most severe form, often fatal without treatment); cutaneous (the most common); and mucocutaneous. Chagas’ disease – caused by Trypanosoma cruzi and predominantly spread by the blood-sucking triatomine bug – has two stages. Symptoms in the acute stage are often mild or absent, resulting in under-diagnosis. Left untreated, infected individuals will progress to the chronic second stage, and 20-30% will develop life-threatening complications. Sleeping sickness is caused by the parasite Trypanosoma brucei and spread by tsetse flies. It also has two stages, with early-stage disease symptoms difficult to distinguish from other viral illnesses. In late-stage disease, the parasite infects the brain and central nervous system, causing confusion and – without treatment – coma and death.
Kinetoplastid diseases (Chagas’ disease, leishmaniasis and HAT) lack approved vaccines, and current development efforts are in their early stages. Chagas’, however, has a relatively full preclinical pipeline and leishmaniasis a candidate in Phase II trials. Many gaps remain with respect to diagnosis: HAT requires a point-of-care test for T.b. rhodesiense (r-HAT), simpler confirmatory tests, tests of cure and high-volume testing on dried blood samples as endemic countries move towards surveillance and/or post-elimination maintenance. The existing cutaneous leishmaniasis diagnostic, CL Detect, failed to demonstrate satisfactory standalone accuracy in various endemic settings including Morocco, Afghanistan and Ethiopia, underlining the importance of novel diagnostic tools, while Chagas’ needs tests of cure and for congenital infection. Improved and safer drugs are needed, particularly for r-HAT, pregnant women infected with Chagas’, and oral drug regimens in leishmaniasis. Biologics and therapeutic vaccines are of particular interest for Chagas’, but still lack either a mature candidate or approved product.
ChAd63-KH, a vectored Leishmania therapeutic vaccine with demonstrated safety and immunogenicity, completed a Phase IIb efficacy trial for treating PKDL in 2023. Trial results published in 2023 showed acoziborole, a novel compound with the potential to be used as a one-day, single-dose treatment for sleeping sickness caused by T.b. gambiense, to be efficacious, with a cure rate of over 95%. A clinical trial is also underway investigating acoziborole for a paediatric indication.