SHE - Strategies for Hookworm Eradication (SHE): Harnessing the parasite developmental keys for designing targeted clinical approaches
Hookworm (Necator americanus or Ancylostoma duodenale) infections represent a major neglected tropical disease, affecting 700 million people worldwide and causing morbidity due to their impact on nutrient uptake and their need to feed on host blood resulting in severe anemia. Hookworm mainly infects people living in impoverished conditions without access to adequate sanitation and is characterized clinically by anemia, malnutrition in pregnant women, and an impairment of the growth and cognitive development of children. While the host immune response to hookworm infection is relatively robust, activating both strong humoral and cellular immune responses, it fails to elicit protection, and people tend to exhibit heavier worm burdens with age.
To date, there is no anti-helminth vaccine, and chemotherapy is the current treatment of choice. However, of the four chemotherapeutic agents currently available against soil-transmitted helminths, all target worm motility and only albendazole produces adequate efficacy against Hookworm. As a consequence, current control strategies rely solely on regular mass treatment with albendazole in at-risk human populations. Given widespread drug resistance in helminth of livestock animals, together with the current strategy of repeated mass administration of monotherapies to humans, there are grave concerns about the development of drug-resistance in human parasites. Thus, there is a pressing need for both the identification of new vaccine targets and the development of new anthelmintic drugs, particularly those that target novel molecular pathways in parasites.
The overarching goal of this research proposal is to identify new intervention strategies against soil-transmitted helminths, and in particular against hookworms. More specifically, the programme of research will focus on two complementary approaches: i) the identification of compounds that can be used as drugs, which target biological pathways of importance in the development, establishment and survival of soil-transmitted helminths, and; ii) the identification of new vaccine targets that could be used to block the establishment of the parasite. These could then be used to create a combined vaccine with the current lead hookworm vaccine antigen Aspartic protease 1 (APR-1).