Malaria has plagued humankind for more than 4,000 years, causing every second human death since the Middle Ages. There has never been an effective vaccine against malaria or any other human parasite, mostly because they tend to be very complex, single-celled organisms (malaria, sleeping sickness, Leishmania) or complex multicellular organisms, like the worms that cause lymphatic filariasis and schistosomiasis.
Moreover, according to the Entomological Society of America, malaria has been exercising its evolutionary flexibility in various vertebrates (likely including the dinosaurs) for over 100 million years. This means malaria is uniquely adept at survival, including becoming resistant to all of the methods we use to combat it. Resistance has been reported against quinine, chloroquine, mefloquine, pyrimethamine-sulfadoxine and ACTs (artemisinin-based combination therapies, the current front-line malaria treatment). Mosquitoes carrying malaria have even circumvented the bed nets by feeding earlier in the evening, catching people before they retire for the night.