Drug repurposing and human parasitic protozoan diseases

Abstract

Parasitic diseases have an enormous health, social and economic impact and are a particular problem in tropical regions of the world. Diseases caused by protozoa and helminths, such as malaria and schistosomiasis, are the cause of most parasite related morbidity and mortality, with an estimated 1.1 million combined deaths annually. The global burden of these diseases is exacerbated by the lack of licensed vaccines, making safe and effective drugs vital to their prevention and treatment. Unfortunately, where drugs are available, their usefulness is being increasingly threatened by parasite drug resistance. The need for new drugs drives antiparasitic drug discovery research globally and requires a range of innovative strategies to ensure a sustainable pipeline of lead compounds. In this review we discuss one of these approaches, drug repurposing or repositioning, with a focus on major human parasitic protozoan diseases such as malaria, trypanosomiasis, toxoplasmosis, cryptosporidiosis and leishmaniasis.

Keywords: Antiparasitic; Cryptosporidium; Drug repurposing; Leishmaniasis; Malaria; Toxoplasmosis; Trypanosomiasis.

Graphical abstract

Fig. 1

Distribution and disease impact of major human diseases caused by parasitic protozoa. (A–C) Reproduced, with the permission of the publisher, the World Health Organization, Global Health Observatory Map Gallery (World Health Organization). (D) Data reprinted, with minor modification, from Ref. Torgerson and Mastroiacovo (2013) with permission from Elsevier [license# 3266830155236]. Deaths and disability adjusted life years (DALYs) data taken from Lozano et al. (2012), Murray et al. (2012b), Torgerson and Mastroiacovo (2013), World Health Organization (2013).

Fig. 2

Common antiprotozoal “hits” from whole-cell-based screening of clinical drug libraries. “Hits” present in two or more different parasite species from studies shown in Table 3 are shown. For P. falciparum, data are from the three asexual blood stage screens (Chong et al., 2006; Weisman et al., 2006; Yuan et al., 2011). White boxes – either not defined as a “hit” or not present in library screened.