Malaria therapy

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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]

Contents

Background

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  [ ru ] 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]

Related Research Articles

Psychosis is a condition of the mind or psyche that results in difficulties determining what is real and what is not real. Symptoms may include delusions and hallucinations, among other features. Additional symptoms are incoherent speech and behavior that is inappropriate for a given situation. There may also be sleep problems, social withdrawal, lack of motivation, and difficulties carrying out daily activities. Psychosis can have serious adverse outcomes.

<span class="mw-page-title-main">Syphilis</span> Sexually transmitted infection

Syphilis is a sexually transmitted infection caused by the bacterium Treponema pallidum subspecies pallidum. The signs and symptoms depend on the stage it presents: primary, secondary, latent or tertiary. The primary stage classically presents with a single chancre though there may be multiple sores. In secondary syphilis, a diffuse rash occurs, which frequently involves the palms of the hands and soles of the feet. There may also be sores in the mouth or vagina. Latent syphilis has no symptoms and can last years. In tertiary syphilis, there are gummas, neurological problems, or heart symptoms. Syphilis has been known as "the great imitator" because it may cause symptoms similar to many other diseases.

<span class="mw-page-title-main">Fever</span> Raised body temperature due to disease

Fever or pyrexia in humans is a symptom of organism's anti-infection defense mechanism that appears with body temperature exceeding the normal range due to an increase in the body's temperature set point in the hypothalamus. There is no single agreed-upon upper limit for normal temperature: sources use values ranging between 37.2 and 38.3 °C in humans.

<span class="mw-page-title-main">General paresis of the insane</span> Organic mental disorder caused by late-stage syphilis

General paresis, also known as general paralysis of the insane (GPI), paralytic dementia, or syphilitic paresis is a severe neuropsychiatric disorder, classified as an organic mental disorder, and is caused by late-stage syphilis and the chronic meningoencephalitis and cerebral atrophy that are associated with this late stage of the disease when left untreated. GPI differs from mere paresis, as mere paresis can result from multiple other causes and usually does not affect cognitive function. Degenerative changes caused by GPI are associated primarily with the frontal and temporal lobar cortex. The disease affects approximately 7% of individuals infected with syphilis, and is far more common in developing countries where fewer options for timely treatment are available. It is more common among men.

<span class="mw-page-title-main">Roseola</span> Human disease caused by human herpesviruses

Roseola, also known as sixth disease, is an infectious disease caused by certain types of human herpes viruses. Most infections occur before the age of three. Symptoms vary from absent to the classic presentation of a fever of rapid onset followed by a rash. The fever generally lasts for three to five days, while the rash is generally pink and lasts for less than three days. Complications may include febrile seizures, with serious complications being rare.

<span class="mw-page-title-main">Congenital syphilis</span> Presence of syphilis in a baby due to its mother being infected

Congenital syphilis is syphilis that occurs when a mother with untreated syphilis passes the infection to her baby during pregnancy or at birth. It may present in the fetus, infant, or later. Clinical features vary and differ between early onset, that is presentation before 2-years of age, and late onset, presentation after age 2-years. Infection in the unborn baby may present as poor growth, non-immune hydrops leading to premature birth or loss of the baby, or no signs. Affected newborns mostly initially have no clinical signs. They may be small and irritable. Characteristic features include a rash, fever, large liver and spleen, a runny and congested nose, and inflammation around bone or cartilage. There may be jaundice, large glands, pneumonia, meningitis, warty bumps on genitals, deafness or blindness. Untreated babies that survive the early phase may develop skeletal deformities including deformity of the nose, lower legs, forehead, collar bone, jaw, and cheek bone. There may be a perforated or high arched palate, and recurrent joint disease. Other late signs include linear perioral tears, intellectual disability, hydrocephalus, and juvenile general paresis. Seizures and cranial nerve palsies may first occur in both early and late phases. Eighth nerve palsy, interstitial keratitis and small notched teeth may appear individually or together; known as Hutchinson's triad.

<span class="mw-page-title-main">Julius Wagner-Jauregg</span> Austrian physician

Julius Wagner-Jauregg was an Austrian physician, who won the Nobel Prize in Physiology or Medicine in 1927, and is the first psychiatrist to have done so. His Nobel award was "for his discovery of the therapeutic value of malaria inoculation in the treatment of dementia paralytica".

Tick-borne diseases, which afflict humans and other animals, are caused by infectious agents transmitted by tick bites. They are caused by infection with a variety of pathogens, including rickettsia and other types of bacteria, viruses, and protozoa. The economic impact of tick-borne diseases is considered to be substantial in humans, and tick-borne diseases are estimated to affect ~80 % of cattle worldwide. Most of these pathogens require passage through vertebrate hosts as part of their life cycle. Tick-borne infections in humans, farm animals, and companion animals are primarily associated with wildlife animal reservoirs. Many tick-borne infections in humans involve a complex cycle between wildlife animal reservoirs and tick vectors. The survival and transmission of these tick-borne viruses are closely linked to their interactions with tick vectors and host cells. These viruses are classified into different families, including Asfarviridae, Reoviridae, Rhabdoviridae, Orthomyxoviridae, Bunyaviridae, and Flaviviridae.

Cognitive disorders (CDs), also known as neurocognitive disorders (NCDs), are a category of mental health disorders that primarily affect cognitive abilities including learning, memory, perception, and problem-solving. Neurocognitive disorders include delirium, mild neurocognitive disorders, and major neurocognitive disorder. They are defined by deficits in cognitive ability that are acquired, typically represent decline, and may have an underlying brain pathology. The DSM-5 defines six key domains of cognitive function: executive function, learning and memory, perceptual-motor function, language, complex attention, and social cognition.

<span class="mw-page-title-main">Vertically transmitted infection</span> Infection caused by pathogens that use mother-to-children transmission

A vertically transmitted infection is an infection caused by pathogenic bacteria or viruses that use mother-to-child transmission, that is, transmission directly from the mother to an embryo, fetus, or baby during pregnancy or childbirth. It can occur when the mother has a pre-existing disease or becomes infected during pregnancy. Nutritional deficiencies may exacerbate the risks of perinatal infections. Vertical transmission is important for the mathematical modelling of infectious diseases, especially for diseases of animals with large litter sizes, as it causes a wave of new infectious individuals.

<span class="mw-page-title-main">Neurosyphilis</span> Infection of the central nervous system in a patient with syphilis

Neurosyphilis is the infection of the central nervous system in a patient with syphilis. In the era of modern antibiotics, the majority of neurosyphilis cases have been reported in HIV-infected patients. Meningitis is the most common neurological presentation in early syphilis. Tertiary syphilis symptoms are exclusively neurosyphilis, though neurosyphilis may occur at any stage of infection.

<span class="mw-page-title-main">Genital herpes</span> Infection by herpes simplex viruses of the genitals

Genital herpes is a herpes infection of the genitals caused by the herpes simplex virus (HSV). Most people either have no or mild symptoms and thus do not know they are infected. When symptoms do occur, they typically include small blisters that break open to form painful ulcers. Flu-like symptoms, such as fever, aching, or swollen lymph nodes, may also occur. Onset is typically around 4 days after exposure with symptoms lasting up to 4 weeks. Once infected further outbreaks may occur but are generally milder.

<i>Anaplasma phagocytophilum</i> Species of bacterium

Anaplasma phagocytophilum is a Gram-negative bacterium that is unusual in its tropism to neutrophils. It causes anaplasmosis in sheep and cattle, also known as tick-borne fever and pasture fever, and also causes the zoonotic disease human granulocytic anaplasmosis.

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<span class="mw-page-title-main">History of malaria</span>

The history of malaria extends from its prehistoric origin as a zoonotic disease in the primates of Africa through to the 21st century. A widespread and potentially lethal human infectious disease, at its peak malaria infested every continent except Antarctica. Its prevention and treatment have been targeted in science and medicine for hundreds of years. Since the discovery of the Plasmodium parasites which cause it, research attention has focused on their biology as well as that of the mosquitoes which transmit the parasites.

<span class="mw-page-title-main">Pyrotherapy</span> Raising body temperature for medical purposes

Pyrotherapy is a method of treatment by raising the body temperature or sustaining an elevated body temperature using a fever. In general, the body temperature was maintained at 41 °C (105 °F). Many diseases were treated by this method in the first half of the 20th century. In general, it was done by exposing the patient to hot baths, warm air, or (electric) blankets. The technique reached its peak of sophistication in the early 20th century with malariotherapy, in which Plasmodium vivax, a causative agent of malaria, was allowed to infect already ill patients in order to produce intense fever for therapeutic ends. The sophistication of this approach lay in using effective anti-malarial drugs to control the P. vivax infection, while maintaining the fever it causes to the detriment of other, ongoing, and then-incurable infections present in the patient, such as late-stage syphilis. This type of pyrotherapy was most famously used by psychiatrist Julius Wagner-Jauregg, who won the Nobel Prize for Medicine in 1927 for his elaboration of the procedure in treating neurosyphilitics.

<span class="mw-page-title-main">History of syphilis</span>

The first recorded outbreak of syphilis in Europe occurred in 1494/1495 in Naples, Italy, during a French invasion. Because it was spread geographically by French troops returning from that campaign, the disease was known as "French disease", and it was not until 1530 that the term "syphilis" was first applied by the Italian physician and poet Girolamo Fracastoro. The causative organism, Treponema pallidum, was first identified by Fritz Schaudinn and Erich Hoffmann in 1905 at the Charité Clinic in Berlin. The first effective treatment, Salvarsan, was developed in 1910 by Sahachiro Hata in the laboratory of Paul Ehrlich. It was followed by the introduction of penicillin in 1943.

<span class="mw-page-title-main">Meningeal syphilis</span> Medical condition

Meningeal syphilis is a chronic form of syphilis infection that affects the central nervous system. Treponema pallidum, a spirochate bacterium, is the main cause of syphilis, which spreads drastically throughout the body and can infect all its systems if not treated appropriately. Treponema pallidum is the main cause of the onset of meningeal syphilis and other treponemal diseases, and it consists of a cytoplasmic and outer membrane that can cause a diverse array of diseases in the central nervous system and brain.

Immuno-psychiatry, according to Pariante, is a discipline that studies the connection between the brain and the immune system. It differs from psychoneuroimmunology by postulating that behaviors and emotions are governed by peripheral immune mechanisms. Depression, for instance, is seen as malfunctioning of the immune system.

<span class="mw-page-title-main">Hobart Reimann</span> American physician

Hobart Ansteth Reimann (1897–1986) was an American virologist and physician. Reimann made contributions to medicine with his 1938 landmark article on atypical pneumonia ; and articles on periodic disease and the common cold (1948). He was active in the testing of streptomycin against typhoid, with "the first publicly reported successful experiments."

References

  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. PMC   1046408 . 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. S2CID   4774586.
  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. S2CID   54264869.
  6. 1 2 3 4 5 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. 1 2 3 Zakon, S. J. (1943). "Alexander Samoilovich Rosenblium: His Contribution to Fever Therapy". Archives of Dermatology and Syphilology. 48 (1): 52–59. doi:10.1001/archderm.1943.01510010056009.
  8. 1 2 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. PMC   3670443 . PMID   23766744.
  9. ↑ Gerstmann, Josef (1928). Die Malariabehandlung der Progressiven Paralyse (in German) (Zweite, Neubearbeitete und Wesentlich vermehrte Auflage ed.). Springer-Verlag. p. 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. 1 2 3 Bruetsch, Walter L. (1944). "Priority on the Discovery of Fever Therapy in Psychosis". 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". 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". 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. PMC   3956094 . 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.
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