Biology:Malaria therapy

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Short description: Medical procedure of treating diseases using artificial injection of malaria parasites

The malaria therapy (or malaria inoculation,[1] and sometimes malariotherapy[2]) is an archaic medical procedure of treating diseases using artificial injection of malaria parasites.[3] It is a type of pyrotherapy (or pyretotherapy) by which high fever is induced to stop or eliminate symptoms of certain diseases. In malaria therapy, malarial parasites (Plasmodium) are specifically used to cause fever, and an elevated body temperature reduces the symptoms of or cure the diseases. As the primary disease is treated, the malaria is then cured using antimalarial drugs.[4] The method was developed by Austrian physician Julius Wagner-Jauregg in 1917 for the treatment of neurosyphilis for which he received the 1927 Nobel Prize in Physiology or Medicine.[5]


The beneficial effects of infections in mental problems were known in the Ancient world. Hippocrates in the 4th century BCE recorded bacterial infections such as dysentery and dropsy reducing the symptoms of madness; and that malaria (quartan fever) could stop epileptic convulsions. Galen in the 2nd century CE described a case of mental illness that ended after malarial infection. There are medical records from the 19th century which indicate that insanity stopped temporarily or permanently when the individuals had severe infections.[6]

Russian psychiatrist Alexander Samoilovich Rosenblum was the first to experimentally use infections for the treatment of psychosis. In 1876, he induced fever in psychotic individuals using malaria, typhoid, and relapsing fever. He claimed that he cured 50% of all those he treated. However, his work was not widely known as his publication in 1877 was in a small journal in Odesa, Ukraine, and written in Russian.[7] He also preferred not to spread his findings. He understood that it was a dangerous experiment and potentially controversial.[8] It was, however, reported by J. Motschukoffsky in a German medical journal Centralblatt für die Medicinischen Wissenschaften,[9] but the underlying cause of how malaria cured psychosis was not understood, and Rosenblum's experiment remained unknown for several decades.[10] Rosenblum never repeated the study or tried to develop specific method for the medical treatment.[11] The importance of the study was realised only in 1938 when Austrian physician Julius Wagner-Jauregg discussed the research at the International Neurological Congress in London.[12]

In 1943, Samuel J. Zakon at the Northwestern University Medical School in Chicago, US, acquired the original paper of Rosenblum and published an English translation with commentary in the Journal of the American Medical Association.[7] The commentary concluded:

Rosenblium [alternative spelling[11][13]] was certainly the first to appreciate the curative effect of fever itself on the psychoses. He understood and reported on the value of malaria and typhoid in the treatment of mental disease. He was the first to inoculate psychotic patients with a febrile disease. Rosenblium, though practically forgotten for over half a century, must be acknowledged as the true pioneer in this field.[8][7]

Rediscovery and clinical application

Although the priority of using malaria therapy in brain disorders is generally attributed to Rosenblum, the credit of developing malaria therapy as a standard medical practice and explaining the underlying scientific principle is to Austrian physician Julius Wagner-Jauregg.[11][14] Wagner-Jauregg, working at the First Psychiatry Clinic at the Asylum of Lower Austria, investigated cases of brain disorders since 1883, publishing his first paper on psychosis in 1887 titled "Über die Einwirkung fieberhafter Erkrankungen auf Psychosen" ("The Effect of Feverish Disease on Psychoses").[6] He soon realised that a severe type of psychosis was related to neurosyphilis, an infection of the central nervous system with syphilis (caused by a bacterium identified in 1905 as Spirochaeta pallida, later renamed Treponema pallidum[15]). Syphilis was at the time a deadly disease characterised by delusions, paralysis, and dementia; and known as "The Great Pox" and the "disease of the century."[6] Neurosyphilis was prevalent in Europe during the 19th century, leading to an increased asylum population during this period.[16]

Wagner-Jauregg came to the conclusion that fever could cure psychosis after reviewing his own experiments and the historical accounts based on three phenomena: (a) the appearance of fever coincided with the disappearance of the symptoms of psychosis in medical history; (b) his findings that fever was the only possible cause for the cure of psychosis; and (c) although all psychotic individuals were not cured, the number of cures increased whenever malaria spread.[6] He made three postulates:

  1. The agent of treatment, febrile disease, while curing mental disorder, can still induce disease in healthy people.
  2. Febrile disease strengthens (makes healthier) individuals with mental disorder.
  3. Elevation of body temperature due to febrile disease is key to suppressing psychotic symptoms.[6]


  1. Ironside, Redvers N. (1925). "On the Treatment of General Paralysis by Malaria Inoculation". British Journal of Venereal Diseases 1 (1): 58–63. doi:10.1136/sti.1.1.58. PMID 21772478. 
  2. Austin, S. C.; Stolley, P. D.; Lasky, T. (1992). "The history of malariotherapy for neurosyphilis. Modern parallels". JAMA 268 (4): 516–519. doi:10.1001/jama.1992.03490040092031. PMID 1619744. 
  3. Kohl, F. (1993). "Wagner von Jauregg and development of malaria therapy". Psychiatrische Praxis 20 (4): 157–159. ISSN 0303-4259. PMID 8362029. 
  4. Daey Ouwens, Ingrid M.; Lens, C. Elisabeth; Fiolet, Aernoud T. L.; Ott, Alewijn; Koehler, Peter J.; Kager, Piet A.; Verhoeven, Willem M. A. (2017). "Malaria Fever Therapy for General Paralysis of the Insane: A Historical Cohort Study". European Neurology 78 (1–2): 56–62. doi:10.1159/000477900. PMID 28633136. 
  5. Raju, T. N. (1998). "The Nobel chronicles. 1927: Julius Wagner-Jauregg (1857-1940)". Lancet 352 (9141): 1714. doi:10.1016/s0140-6736(05)61500-0. PMID 9853480. 
  6. 6.0 6.1 6.2 6.3 6.4 Lipper, S.; Werman, D. S. (1977). "Schizophrenia and intercurrent physical illness: a critical review of the literature". Comprehensive Psychiatry 18 (1): 11–22. doi:10.1016/s0010-440x(77)80003-5. ISSN 0010-440X. PMID 318959. 
  7. 7.0 7.1 7.2 Zakon, S. J. (1943). "Alexander Samoilovich Rosenblium: His Contribution to Fever Therapy" (in en). Archives of Dermatology and Syphilology 48 (1): 52–59. doi:10.1001/archderm.1943.01510010056009. 
  8. 8.0 8.1 Tsay, Cynthia J. (2013). "Julius Wagner-Jauregg and the legacy of malarial therapy for the treatment of general paresis of the insane". The Yale Journal of Biology and Medicine 86 (2): 245–254. ISSN 1551-4056. PMID 23766744. 
  9. Gerstmann, Josef (1928) (in De). Die Malariabehandlung der Progressiven Paralyse (Zweite, Neubearbeitete und Wesentlich vermehrte Auflage ed.). Vienna. pp. 291. ISBN 978-3-7091-2192-4. OCLC 913702988. 
  10. Wagner-Jauregg, J.; Bruetsch, W. L. (1946). "The history of the malaria treatment of general paralysis". The American Journal of Psychiatry 102 (5): 577–582. doi:10.1176/ajp.102.5.577. PMID 21026839. 
  11. 11.0 11.1 11.2 Bruetsch, Walter L. (1944). "Priority on the Discovery of Fever Therapy in Psychosis" (in en). Journal of the American Medical Association 125 (3): 228. doi:10.1001/jama.1944.02850210050023. ISSN 0002-9955. 
  12. Gonda, V. E. (1957). "Wagner-Jauregg and the priority of producing artificial fever for treatment of general paresis". The American Journal of Psychiatry 114 (6): 561–562. PMID 13478779. 
  13. Reynolds, Frank W. (1947). "Syphilis: A Review of the Recent Literature" (in en). Archives of Internal Medicine 79 (1): 92–112. doi:10.1001/archinte.1947.00220070088001. ISSN 0730-188X. PMID 20283865. 
  14. Fleischmann, Walter (1944). "Priority in the Discovery of Fever Therapy in Psychosis" (in en). Journal of the American Medical Association 125 (3): 228. doi:10.1001/jama.1944.02850210050025. ISSN 0002-9955. 
  15. Tampa, M.; Sarbu, I.; Matei, C.; Benea, V.; Georgescu, S. R. (2014). "Brief history of syphilis". Journal of Medicine and Life 7 (1): 4–10. ISSN 1844-3117. PMID 24653750. 
  16. Scheck, D. N.; Hook, E. W. (1994). "Neurosyphilis". Infectious Disease Clinics of North America 8 (4): 769–795. doi:10.1016/S0891-5520(20)30626-7. ISSN 0891-5520. PMID 7890932.