Investigators at the University of Melbourne and Monash University identified compounds that inhibit the barber’s pole worm, and were interested in screening them against other infectious worms. BVGH connected them with an investigator at University of Buea, who is developing inhibitors against Onchocerca. The University of Buea will screen the University of Melbourne compounds against Onchocerca volvulus to identify potential drug candidates.
Malaria kills almost half a million people each year, mostly young children in sub-Saharan Africa. Decreased sensitivity of malaria parasite field isolates to artemisinin, the most recent antimalarial to be used in the field, is emerging, and it is of crucial importance to maintain an active research to develop new interventions. People living in malaria endemic areas develop naturally acquired immunity (NAI) after repeated exposure to malaria. However, the mechanism of NAI is not well understood. The fellowship aims to improve the understanding of how naturally acquired immunity works to protect against clinical malaria. For that purpose, the host scientists Darren Creek and Christian Doerig at Monash University, Australia, and the fellow Abdirahman Abdi from the Kenya Medical Research Institute have conducted controlled human malaria infection on Kenyan adults who had had varying levels of prior exposure to natural malaria infection.
Malaria is a major public health threat in sub-Saharan Africa, and drug resistance is a major threat to current control efforts. Resistance to traditional antimalarials, including chloroquine and the antifolates, is widespread among the major causative parasite, Plasmodium falciparum. Artemisinin combination therapies, comprising an artemisinin derivative combined with a longer-acting partner drug such as lumefantrine or piperaquine, are the recommended treatment for falciparum malaria. However, resistance to the partner drugs is now widespread, and artemisinin resistance has recently spread throughout South-East Asia. Alarming reports of artemisinin resistance in sub-Saharan Africa are beginning to emerge, and improved methods to detect and monitor drug resistance in the field are urgently required.
The fellow Deus Ishengoma has an established research program monitoring antimalarial drug resistance in Tanzania, and aims to improve detection tools to allow routine monitoring in field settings. The host scientists Christian Doerig and Darren Creek at Monash University have developed advanced techniques for system-wide biochemical analysis of malaria parasites. These mass spectrometry and infrared (ATR-IR) spectroscopy approaches allow highly sensitive metabolomics and proteomics analyses, and may provide an alternative approach for detecting drug resistance phenotypes to established genetic tools such as mutation-dependent PCR tests.
Recent work from Darren Creek has revealed that the levels of a specific protein (Kelch13), haemoglobin-derived peptides and antioxidant molecules are associated with artemisinin-resistant parasites of South-East Asian origin (Siddiqui G, et al., J Infect Dis. In press). The collaboration wants to determine whether the abundance of these, or other specific molecules, is also associated with drug resistance in African parasites. The hypothesis that underlies this project is that metabolite and/or protein signatures of drug resistance will allow the development of point-of-care testing devices for antimalarial drug resistance.