Immunity, drug efficacy and spread of antimalarial drug resistance

Artemisinin Combination Therapy has played a fundamental role in controlling malaria and more than 70 percent of clinical cases globally rely on this therapy to treat this devastating disease. Given how much we depend on Artemisinin Combination Therapy, it is extremely alarming that resistance is now established throughout Southeast Asia, and its spread is now being reported in the Pacific and Africa.

Antimalarial drug resistance is evaluated by examining drug efficacy, which is determined by observing how long a patient takes to clear parasites from their blood. This evaluation is severely impeded by the presence of immunity to malaria which acts by reducing the number of parasites in the blood and improving rates of parasite clearance during drug treatment. The implications are that in areas with high immunity, clinicians and scientists will believe that the drugs are working better than they actually are and early signs of emerging drug resistance will go unnoticed.

Surprisingly, no study has investigated how antimalarial immunity facilitates parasite clearance during treatment with Artemisinin Combination Therapy, and how immunity may mask the emergence of drug resistance. The aim of the proposed study is to understand how host human immunity can interfere with evaluating how well antimalarial drugs work. This knowledge will be used to effectively monitor emerging Artemisinin Combination Therapy resistance.

2019-2024

Utilising patient samples collected through multinational therapeutic efficacy studies of Artemisinin Combination Therapy, we have measured antimalarial antibodies and their functional properties to a range of parasite targets by high throughput immunoassay and demonstrated that antimalarial immunity significantly influences the phenotype of drug resistant Plasmodium falciparum and thus surveillance of emerging resistance to first line antimalarial treatments. We are continuing to monitor this association as novel treatment regimens are rolled out and the transmission of malaria and therefore acquisition of antimalarial immunity in endemic regions changes.

This research provides solid evidence base for defining and quantitating the targets of host immunity that influence antimalarial efficacy. Identifying immune biomarkers that predict antimalarial drug efficacy is needed to ensure accurate measurements of drug efficacy and to effectively monitor emerging drug resistance. Ultimately, this workwill enable us to provide the most accurate estimates of antimalarial drug efficacy and will allow scientists to evaluate the spread of resistance to Artemisinin Combination Therapy to the highest degree. This is particularly imperative to prevent the global spread of resistance to Artemisinin Combination Therapy, which is currently a World Health Organization (WHO) priority.