Discovery of Malaria Inoculation to Treat Dementia Paralytica by https://padlet.com/alexwillingham30/Bookmarks Discovered in 1927 by Julius Wagner-Jauregg en-us 2022-03-26 18:28:59 UTC 2022-04-24 20:16:09 UTC hello@padlet.com Malaria alexwillingham30 https://padlet.com/alexwillingham30/Bookmarks/wish/2150780926 3
Malaria is a parasitic disease that is spread through humans by infected mosquitos. Malaria is fairly common in tropical climates rather than temperate climates where this is rarely an occurrence. Symptoms include: fever, chills, and an overall sick feeling.

In 1878, Alphonse Laveran (a French military doctor) was posted in Algeria within military hospitals. Since Malaria was so prevalent within armies, Alphonse Laveran ended up diving deep into the disease's clinical and physiological aspects.

Originally, they thought that Malaria was caused by some pollutant in the marshland soil ("bad air" from the marshlands). Eventually his research led him to examining the blood of patients, which led him to the life cycle of malaria parasites which occurs in the stomach of Anopheles mosquito.

Source (1) https://www.mayoclinic.org/diseases-conditions/malaria/symptoms-causes/syc-20351184#:~:text=Malaria%20is%20a%20disease%20caused,in%20tropical%20and%20subtropical%20countries.
Souce (2) https://www.cdc.gov/malaria/about/history/laveran.html]]> 2022-04-20 17:58:50 UTC https://padlet.com/alexwillingham30/Bookmarks/wish/2150780926 Dementia Paralytica Disease and Notable Cases alexwillingham30 https://padlet.com/alexwillingham30/Bookmarks/wish/2150782227 1
Dementia Paralytica (or general paresis of the insane) is a chronic psychosis of middle age and it is characterized by progressive mental deterioration. It has symptoms of excitation of the central nervous system, leading to dementia, speech defects, and paralysis. It is a late manifestation of syphilis and it often occurs up to 15 years after the initial infection.

Definitive diagnosis is based on the analysis of cerebrospinal fluid and tests for syphilis. Although there were recorded cases of remission of the symptoms, especially if they had not passed beyond the stage of psychosis, these individuals almost invariably experienced relapse within a few months to a few years.

Some notable cases of Dementia Paralytica include Theo Van Gogh, the brother of Vincent van Gogh, died six months after Vincent in 1891 from this disease. Al Capone died of syphilitic paresis, having contracted syphilis in a brothel in 1919, and not having been properly treated for it in time to prevent his later onset of syphilitic paresis. General Ranald S. Mackenzie was retired from the US Army in 1884 for "general paresis of the insane" 5 years before his death in 1889.

Source (1) https://psycnet.apa.org/buy/2009-01809-012 
Source (2) https://www.collinsdictionary.com/us/dictionary/english/dementia-paralytica  
Source (3) https://en.wikipedia.org/wiki/General_paresis_of_the_insane
]]> 2022-04-20 17:59:45 UTC https://padlet.com/alexwillingham30/Bookmarks/wish/2150782227 Current Treatment of Dementia Paralytica (contemporary) alexwillingham30 https://padlet.com/alexwillingham30/Bookmarks/wish/2150782910 11
There was a gradual decline in the number of articles and a final plateau of around 30 articles per year in 1942. The subsequent plateau in the number of articles occurred due to John Mahoney’s paper in 1943 describing the success of penicillin in treating syphilis.

Penicillin has some ameliorative effect in every stage of neurosyphilis. Meningovascular disease responds most dramatically. Once anatomic damage has occurred, penicillin is not effective in restoring lost function. In addition, blindness secondary to primary optic atrophy or 8th nerve deafness responds poorly to any type of treatment. Penicillin schedules employing more than 5 million units appear more effective than lower dose regimens.

By 1947, penicillin had been shown to be an effective cure for early syphilis and was becoming widely used to treat the disease, and this method is still used today. According to the CDC, Penicillin G, administered parenterally, is the preferred drug for treating patients in all stages of syphilis. The preparation used (i.e., benzathine, aqueous procaine, or aqueous crystalline), dosage, and length of treatment depend on the stage and clinical manifestations of the disease. This information is up to date since March 30, 2022.


Source (1) https://www.jstor.org/stable/44972676?seq=1
Source (2) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3670443/
Source (3) https://en.wikipedia.org/wiki/History_of_syphilis#:~:text=The%20study%20began%20in%201932,used%20to%20treat%20the%20disease.
Source (4) https://www.cdc.gov/std/treatment-guidelines/syphilis.htm#:~:text=Penicillin%20G%2C%20administered%20parenterally%2C%20is,clinical%20manifestations%20of%20the%20disease.

]]> 2022-04-20 18:00:13 UTC https://padlet.com/alexwillingham30/Bookmarks/wish/2150782910 Julius Wagner-Jauregg alexwillingham30 https://padlet.com/alexwillingham30/Bookmarks/wish/2150787163 12
Julius Wagner-Jauregg (March 7th, 1857 – September 27th, 1940) 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. He was born and raised in Wels, Upper Austria.

He attended the Schottengymnasium in Vienna before going on to study Medicine at the University of Vienna from 1874 to 1880, where he also studied with Salomon Stricker in the Institute of General and Experimental Pathology. He obtained his doctorate in 1880, but then left the institute in 1882. Later in life when he retired, many schools, roads and hospitals are named after him in Austria.

Towards his last days Wagner-Jauregg was influenced by Hitler's German nationalism, and became an anti-Semite[7] and sympathizer of Nazism. Documentary evidence indicates that he supported the Nazi party shortly after the invasion of Austria in 1938 by Germany. However, a denazification commission in Austria found that his application for NSDAP membership had been refused "...on grounds of race", as his first wife Balbine Frumkin was Jewish.

Source (1) https://en.wikipedia.org/wiki/Julius_Wagner-Jauregg

]]> 2022-04-20 18:03:08 UTC https://padlet.com/alexwillingham30/Bookmarks/wish/2150787163 Modern Day Thoughts on Dementia Paralytica Treatment with Malaria alexwillingham30 https://padlet.com/alexwillingham30/Bookmarks/wish/2150801905 10
The reported treatment outcome appeared very favorable for a previously considered untreatable condition. However, the evidence to support the efficacy of malaria fever therapy was weak, researchers conclude. In 1933, malaria fever therapy was not yet subjected to a standardized set of regulatory research criteria. While at that time any drug used in the treatment of patients was controlled with formal standards including animal research, toxicity tests, histopathological studies, tests of therapeutic efficacy, and approval by a federal regulatory board. Only observational studies were available with many differences in often poorly described patient characteristics and diagnostic criteria.

 According to researchers, it was not possible to isolate the effect of the induced fever in itself from the effect of concomitant heavy metal therapy and general hygiene strategies taken to improve the patient’s general health. Fresh air, good nutrition, massage, hydrotherapy, and the elimination of physical and mental stress were implemented in the hope of increasing the bodily defense against the syphilitic infection and to strengthen the condition of the patients prior to the exhausting effects of malaria fever therapy.

The history of malaria fever therapy teaches us that a compelling need to contribute to the solution of a global health problem may compromise critical appraisal; in this example the situation led to the introduction of a globally applied and Nobel Prize-awarded treatment of uncertain benefit. Therefore, even in the midst of a pandemic, it is necessary to find the right balance between the rapid availability of therapeutic and preventive measures on the one hand, and careful research and ethical considerations on the other. 

Source (1) https://worldneurologyonline.com/article/treatment-evaluation-takes-time/]]> 2022-04-20 18:13:09 UTC https://padlet.com/alexwillingham30/Bookmarks/wish/2150801905 "On the Effect of Feverish Disease on Psychoses" published in 1887 alexwillingham30 https://padlet.com/alexwillingham30/Bookmarks/wish/2150828102
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Wagner-Jauregg was also interested in trauma, nerve action, and shock therapy. His experiments on shock therapy led him to consider the possible value of fever in the treatment of mental illness. In 1887 he published his first paper on the effects of fevers on psychosis.

According to Wagner-Jauregg, the mental state of his patients seemed to improve after they recovered from a febrile illness. He thought patients with paresis, or dementia paralytica associated with advanced syphilis, particularly benefited from episodes of high fever.

By 1917 he concluded that the pyretic agents he had been using did not produce a permanent cure. He then decided to test malaria therapy, confident that, after he had cured the patient of syphilitic paresis, he could cure the malaria with quinine. 

Source (1)
https://www.jameslindlibrary.org/articles/julius-wagner-jauregg-pyrotherapy-simultanmethode-and-racial-hygiene/
Source (2) https://www.encyclopedia.com/science/encyclopedias-almanacs-transcripts-and-maps/julius-wagner-jauregg]]> 2022-04-20 18:30:17 UTC https://padlet.com/alexwillingham30/Bookmarks/wish/2150828102 Pyrotherapy Experiments alexwillingham30 https://padlet.com/alexwillingham30/Bookmarks/wish/2150830575 4
Pyrotherapy is a method of treatment by raising the body temperature or sustaining an elevated body temperature using a fever. 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. 

Since antiquity, claims had been made about the beneficial effects of fever on psychotic symptoms , and Wagner-Jauregg became interested in this topic through observations of his own patients. The general paresis of the insane caused by neurosyphilis was effectively overcome by the method.

Pyrotherapy was also employed in psychiatry. Of note here is the use of sulfozinum and pyrogenal that was relatively widespread in Soviet psychiatry. Against schizophrenia "Saprovitan" and "Pyrifer" were tried.

Source (1) https://www.jameslindlibrary.org/articles/julius-wagner-jauregg-pyrotherapy-simultanmethode-and-racial-hygiene/
Source (2) https://en.wikipedia.org/wiki/Pyrotherapy]]> 2022-04-20 18:32:10 UTC https://padlet.com/alexwillingham30/Bookmarks/wish/2150830575 Nobel Piece Prize in 1927 alexwillingham30 https://padlet.com/alexwillingham30/Bookmarks/wish/2150832648 7
In 1927 Julius Wagner-Jauregg won the Nobel Prize for his inoculation of malaria with dementia paralytica patients. The main work pursued by Wagner-Jauregg throughout his life was related to the treatment of mental disease by inducing a fever. In 1887 he investigated the effects of febrile diseases on psychoses, making use of erisipela and tuberculin (discovered in 1890 by Robert Koch).

Since these methods of treatment did not work very well, he tried in 1917 the inoculation of malaria parasites, which proved to be very successful in the case of dementia paralytica (also called GPI), caused by neurosyphilis, at that time a terminal disease. It had been observed that some who develop high fevers could be cured of syphilis.

From 1917 to the mid 1940s, malaria induced by the least aggressive parasite, Plasmodium vivax, was used as treatment for tertiary syphilis because it produced prolonged and high fevers. This was considered an acceptable risk because the malaria could later be treated with quinine, which was available at that time. His main publication was a book titled Verhütung und Behandlung der progressiven Paralyse durch Impfmalaria (Prevention and treatment of progressive paralysis by malaria inoculation).

Source (1) https://en.wikipedia.org/wiki/Julius_Wagner-Jauregg#:~:text=Julius%20Wagner%2DJauregg%20(7%20March,the%20treatment%20of%20dementia%20paralytica%22.
Source (2) https://www.jameslindlibrary.org/articles/julius-wagner-jauregg-pyrotherapy-simultanmethode-and-racial-hygiene/]]> 2022-04-20 18:33:43 UTC https://padlet.com/alexwillingham30/Bookmarks/wish/2150832648 Simultanmethode alexwillingham30 https://padlet.com/alexwillingham30/Bookmarks/wish/2150841151 8
When a Danish psychiatrist claimed that a new, non-infectious intervention to induce fever would prove better than malaria-therapy, Wagner-Jauregg replied that this was pure speculation and that a direct ‘head-to head’ comparison in similar patients would be the only method to establish superiority of one treatment over another These methodological issues were addressed by Wagner-Jauregg in a paper published in 1931.

Introducing a term in German – Simultanmethode – for the important methodological principle of unbiased allocation to treatment groups using alternation, Julius Wagner-Jauregg added to the earlier introduction of similar terms in English and French. 

One of Wagner-Jauregg’s former assistants reported that Wagner-Jauregg became skeptical about the scientific validity of case series and studies using historical controls during the 1890s. Julius Wagner-Jauregg also became sceptical of his own observations and expectations.  In the late 1890s, to reduce his own subjective impact on his experiments, he began delegating all experimental treatments to his assistants.

Source (1) https://www.jameslindlibrary.org/articles/julius-wagner-jauregg-pyrotherapy-simultanmethode-and-racial-hygiene/]]> 2022-04-20 18:39:39 UTC https://padlet.com/alexwillingham30/Bookmarks/wish/2150841151 History of Dementia Paralytica alexwillingham30 https://padlet.com/alexwillingham30/Bookmarks/wish/2151035333 2
While retrospective studies have found earlier instances of what may have been the same disorder, the first clearly identified examples of paresis among the insane were described in Paris after the Napoleonic Wars. Dementia Paralytica was first described in 1822 by Antoine Laurent Jesse Bayle. By 1877 an asylum for men in New York reported this institution said this disorder accounted for more than 12% of admissions and more than 2% of deaths.

While Friedrich von Esmarch and the psychiatrist Peter Willers Jessen had asserted as early as 1857 that syphilis caused general paresis (progressive Paralyse),progress toward the general acceptance by the medical community of this idea was only accomplished later by the 19th Century syphilographer Jean Alfred Fournier.

In 1917 Julius Wagner-Jauregg discovered that pyrotherapy involving infecting paretic patients with malaria could halt the progression of general paresis. This is then what led to Julius Wagner-Jauregg getting the Nobel Prize.

Source (1) https://en.wikipedia.org/wiki/General_paresis_of_the_insane

]]> 2022-04-20 21:40:15 UTC https://padlet.com/alexwillingham30/Bookmarks/wish/2151035333 Alexander Rosenblum alexwillingham30 https://padlet.com/alexwillingham30/Bookmarks/wish/2152661728 5
Despite the widespread literature discussing the potentially treatment using fevers in treating psychoses, intermittent fevers were not intentionally induced in patients until 1876, when psychiatrist Alexander Rosenblum induced fever using malaria, typhoid, and relapsing fever.

11 of his 22 psychiatric patients were cured after receiving treatment. However, his discovery did not receive widespread attention because his results were published in an obscure journal. Due to the controversial nature of this, especially with the rise of conservatism in Russia, Rosenblum omitted this fact in his article and in his correspondence with B. Oks, who was responsible for sharing these observations with the German scientific community.

Wagner-Jauregg acknowledged that Rosenblum’s experiment was a formative event in his decision to inoculate his patients with GPI with tertian malaria.  Despite this, Rosenblum’s experiment did not gain widespread recognition in the international field of psychiatry until 1943, when S.J. Zakon translated the original article into English.

Source (1) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3670443/]]> 2022-04-21 20:45:33 UTC https://padlet.com/alexwillingham30/Bookmarks/wish/2152661728 Importance of the Nobel Piece Prize alexwillingham30 https://padlet.com/alexwillingham30/Bookmarks/wish/2152671849 9
In addition to his work on the malaria therapy for the treatment of GPI, Wagner-Jauregg also contributed to the use of iodine in salt to prevent the growth of goiters. In Austria, he was a giant among his peers and published numerous scientific works ranging from cretinism in the thyroid to later works on hereditary and eugenics.

The importance of his discovery of the use of malaria for the treatment of psychosis undermined the “therapeutic nihilism” that was being associated with Kraeplin and the neuropsychiatrists. His discovery demonstrated that psychosis could potentially have a natural cause, and Wagner-Jauregg predicted a rosy future for the field of psychiatry, urging his fellow scientists to search for treatments for psychiatric disorders by identifying the organic root of the problem.

In his Nobel Lecture, Wagner-Jauregg emphasized that although the explanatory mechanism for malariotherapy was unknown, it should be classified as a specific rather than a non-specific treatment. This distinction was important because it promoted the idea that induced fever had a direct, specific action on the organic root of GPI rather than a universal, non-specific course. 

Source (1) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3670443/]]> 2022-04-21 20:55:42 UTC https://padlet.com/alexwillingham30/Bookmarks/wish/2152671849