The main work pursued by Wagner-Jauregg throughout his life was related to the treatment of mental disease by inducing a fever, an approach known as pyrotherapy. In 1887 he investigated the effects of febrile diseases on psychoses, making use of erisipela and tuberculin (discovered in 1890 by Robert Koch). Since these methods of treatment did not work very well, he tried in 1917 the inoculation of malariaparasites, which proved to be very successful in the case of dementia paralytica (also called general paresis of the insane), caused byneurosyphilis, at that time a terminal disease. It had been observed that some who develop high fevers could be cured of syphilis. Thus, for a brief time malaria was used as treatment for tertiary syphilis because it produced prolonged and high fevers (a form of pyrotherapy). This was considered an acceptable risk because the malaria could later be treated with quinine, which was available at that time. This discovery earned him the Nobel Prize in Medicine in 1927. His main publication was a book titled Verhütung und Behandlung der progressiven Paralyse durch Impfmalaria (Prevention and treatment of progressive paralysis by malaria inoculation) in the Memorial Volume of the Handbuch der experimentellen Therapie,
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