Healing with malaria: a brief historical review of malariotherapy for neurosyphilis, mental disorders and other infectious diseases.

Ten years ago, two articles about malariotherapy in Chinese human immunodefi ciency virus (HIV) patients once again raised ethical issues about this widely used treatment for infectious and mental diseases. Malariotherapy was born in a context where bioethics was not recognized as we do now, and evidence-based medicine was not yet established. During the pre-penicillin era, there was no effi cient treatment for syphilis. During the natural evolution of the disease, patients sometimes developed neurosyphilis 10 to 25 years after the initial infection. The most severe form of neurosyphilis is general paralysis of the insane (GPI)1, which is fatal in almost all cases because of a progressive degeneration of the nervous system. Physically, GPI is characterized by seizures, ataxia, speech defi cits and general paralysis. Mentally, it causes mania, depression, paranoia, violent behavior, delirium, memory loss, disorientation and apathy2. The curative effect of fevers has been reported since Hippocrates’ time. The Physician of Kos wrote that during and after the intermittent fever, as malaria was then called, patients with mental insanities improved and their aggressiveness was reduced. Reports from the Middle Ages describe improvement in patients in asylums stricken by cholera. In the 15th century, Ruy Diaz de Isla was the fi rst to report that fever had a benefi cial effect on syphilis3. However, 350 years later, Wagner-Jauregg, the father of malariotherapy, described in detail experiments with induced fever in GPI patients. General paralysis of the insane was the main cause of institutionalization in asylums and psychiatric hospitals from the end of 19th century until the 1940s. The prevalence of GPI at that time ranged from 10% to 45% in psychiatric hospitals worldwide1,2.