Theses and Dissertations Collection

In 2020 the World Health Organization reported 241 million cases of malaria, a disease caused by Plasmodium parasites transmitted by Anopheles mosquitoes. Patients with severe malaria can exhibit changes in levels of the biogenic amines histamine and serotonin (5-hydroxytryptamine, 5-HT) in circulating plasma. In mosquitoes, histamine and 5-HT are important neuromodulators that control biology and behavioral responses. Given the altered levels of histamine and 5-HT in response to malaria parasite infection and the importance of these biogenic amines as neuromodulators in insects, the impact of ingested histamine and 5-HT at severe malaria associated concentrations (10 nM histamine and 0.15 µM 5-HT) and healthy concentrations (1nM histamine and 1.5 µM 5-HT) on uninfected Anopheles stephensi behavior and infection success were examined. The studies presented here have demonstrated that mosquitoes ingesting histamine and 5-HT at severe malaria concentrations in human blood exhibit altered biting behavior, flight behavior, and infection success with malaria parasites in a manner predicted to favor parasite transmission. Optimistically, this work and these findings can connect clinical interventions with the delivery of novel lures (i.e., delivery of small molecules at attractive bait stations) to manipulate histamine and 5-HT signaling to be leveraged for malaria control.