Wagner-Jauregg's malaria therapy for neurosyphilis

General paralysis of the insane, the late stage of syphilis in the brain, brought paralysis together with dementia or psychosis, and it usually killed within a few years. It accounted for roughly 5 to 10 percent of psychiatric admissions before 1945. Salvarsan and mercury did little for it. The 1927 Nobel presentation speech put full remissions, spontaneous or treated, at about 1 percent.

Julius Wagner-Jauregg, a Vienna psychiatrist, had been thinking about fever since 1883, when he saw a woman with severe psychosis recover after erysipelas. He published on febrile illness and psychoses in 1887. He tried erysipelas once, with an unfortunate result. Koch's tuberculin, which caused fever, looked better. He began giving it in 1890, stopped for some years after reports of deaths from the drug, and in 1900 and 1901 compared 69 paretic patients given tuberculin with 69 untreated ones. More of the treated patients went into remission.

In 1917 a colleague, Alfred Fuchs, asked him whether a soldier with tertian malaria should get quinine. Wagner-Jauregg took the soldier's blood and injected it into nine patients with general paralysis. After 7 to 12 days of fever they were given quinine and the arsenical Neosalvarsan. In his Nobel lecture Wagner-Jauregg said six of the nine had an extensive remission and three stayed well. A 2013 history by Cynthia Tsay gives a harsher count: one death, two sent to asylums, and four relapses among the six who improved. By late 1921 he reported more than 200 patients treated, 50 of them well enough to go back to work.

Others copied the method quickly. Watson Eldridge gave the first malaria inoculation in the United States in 1922 at St. Elizabeths Hospital in Washington. American and British psychiatrists let infected Anopheles mosquitoes bite their patients, which Wagner-Jauregg opposed in case the insects escaped. A review of 35 studies by 1926 found full remission in 27.5 percent, partial remission in 26.5 percent, and death or no change in 46 percent. Tsay writes that one Swedish professor on the Nobel committee, B. Gadelius, called Wagner-Jauregg a criminal for injecting malaria, and that the prize waited until Gadelius retired.

The patients had not consented to being infected. Penicillin, which John Mahoney reported in 1943 as a treatment for early syphilis, made malaria therapy obsolete. After the Anschluss, Wagner-Jauregg, who wrote on heredity and eugenics late in life, applied twice to join the Nazi Party. He died on 27 September 1940.