Clinical and Parasitological Characteristics of Plasmodium vivax Malaria in Malaria-Naïve Patients: A Review of Malaria Fever Therapy in Patients with Schizophrenia and Neurosyphilis during the 1950s and 1960s in Vienna, Austria.

On the basis of the findings of Austrian psychiatrist Julius Wagner-Jauregg, malaria fever therapy became the standard treatment for end-stage syphilis associated with generalized paralysis in the early 20th century. The parasitological and clinical features of iatrogenically induced Plasmodium vivax malaria in patients with schizophrenia and neurosyphilis during the 1950s and 1960s in Vienna, Austria, are described in the current study. All patients treated for schizophrenia or neurosyphilis at the Department of Psychiatry of the General Hospital of Vienna between 1951 and 1969 who underwent malaria fever therapy were analyzed regarding the parasitological and clinical characteristics of induced malaria. A total of 322 patients who underwent malaria fever therapy were included in the analysis (schizophrenia: n = 147; neurosyphilis: n = 175). The route of inoculation was mainly intravenous, and the dose varied between 4 and 8 mL of blood. The first fever peaks appeared ∼7 days post-inoculation. Temperature increased over time in consecutive fever paroxysms, whereas the afebrile time interval between fever peaks shortened progressively from 41 to 31 hours. After a mean of 5-6 fever peaks, all patients received standard antimalarial therapy with quinine monotherapy or combination therapy. These data reveal that the extra-hepatic incubation period of P. vivax is ∼7 days after intravenous inoculation. The current study reveals a surprisingly short periodicity between fever paroxysms, shedding light on the natural course of infection. The evaluation of historic patient data from malaria fever therapy provides a unique opportunity to study the clinical and parasitological features of untreated malaria.