Malaria therapy in Spain: 100 years after its introduction as a treatment for the general paralysis of the insane.

This article addresses the implementation of malaria fever therapy in Spain. Neuropsychiatrist Rodríguez-Lafora first used it in 1924, but Vallejo-Nágera was the main advocate for the technique. He had learned the method from Wagner von Jauregg himself, and he worked in the Military Psychiatric Clinic and the San José Mental Hospital, both in Ciempozuelos (Madrid). Vallejo-Nágera worked with the parasitologist Zozaya, who had travelled to England with a Rockefeller Foundation grant in order to learn from British malariologist, Sydney Price James. This article details the results of the uneven implementation of this treatment in Spanish psychiatric institutions. Although syphilologists and internists used fever therapy for the treatment of general paralysis of the insane, they were much less enthusiastic than psychiatrists.

Malaria Fever Therapy for General Paralysis of the Insane: A Historical Cohort Study.

BACKGROUND/AIMS: This year marks the 100th anniversary of the first malaria fever treatment (MFT) given to patients with general paralysis of the insane (GPI) by the Austrian psychiatrist and later Nobel laureate, Julius Wagner-Jauregg. In 1921 Wagner-Jauregg reported an impressive therapeutic success of MFT and it became the standard treatment for GPI worldwide. In this study, MFT practice in the Dutch Vincent van Gogh psychiatric hospital in GPI patients who had been admitted in the period 1924-1954 is explored. METHODS: To identify patients with GPI, cause-of-death statistics was used. Data on MFT were retrieved from annual hospital reports and individual patient records. RESULTS: Data on MFT were mentioned in the records of 43 out of 105 GPI patients. MFT was practiced in a wide range of patients with GPI, including those with disease duration of more than 1 year, up to 70 years of age, and those with a broad array of symptoms and comorbidities, such as (syphilitic) cardiac disease. Inoculation with malaria was done by patient-to-patient transmission of infected blood. CONCLUSIONS: MFT practice and mortality rates in MFT-treated patients correspond to similar findings worldwide. MFT was well tolerated and MFT-treated patients had a significantly longer survival.

Malariablood in the pocket. / Malariablut in der Westentasche.

For the first time on June 5, 1919, at the Hamburg State Hospital Friedrichsberg, two paralytics were artificially infected with malaria, subjecting them to the new malaria fever treatment according to Wagner-Jauregg (1917). This article examines the life stories and medical histories of these patients, an opera singer and a yardmaster, and provides an interpretation based on their medical files. Relevant contemporary medical publications contextualise the specific configurations of their hospital stay. In both cases, a detailed comparison between each medical file and the published case history reveals remarkable.discrepancies. A specific concept of remission, mainly determined by the level of restoration of a patient's working power, i. e. the ability to work, was implemented. Finally, the article considers the question of why the new therapy method was introduced in Hamburg specifically on June 5, 1919.

Pyrotherapy for the Treatment of Psychosis in the 21st Century: A Case Report and Literature Review.

The concept that fevers can improve the condition of patients with certain medical and psychiatric diseases dates back to Hippocrates. Over the centuries, it has been observed that fevers and infectious agents have been beneficial for a broad spectrum of diseases, including neurologic conditions such as epilepsy and psychiatric illnesses including melancholy and psychosis. Interest in the concept of fever as a treatment for disease, termed pyrotherapy or pyretotherapy, peaked in the late 1800s and early 1900s thanks to the Nobel Prize winning work of Julius Wagner-Jauregg for his studies with malaria therapy for general paralysis of the insane, now more commonly referred to as neurosyphilis. The use of inoculations of infectious agents for their fever-inducing effects in the treatment of neurosyphilis quickly spread throughout the world, and, by the 1920s, it was considered by many to be the treatment of choice for neurosyphilis as well as other psychotic disorders. However, with the discovery of penicillin for the treatment of syphilis, which coincided with the advent of convulsion-oriented practices including electroconvulsive therapy and insulin coma for the treatment of psychotic disorders, pyrotherapy soon lost favor among psychiatrists and, since the 1950s, it has largely been overlooked by the scientific community. In this article, the authors provide a brief literature review of the history of pyrotherapy and present a case report of a woman with schizoaffective disorder and severe psychotic symptoms who experienced a remarkable resolution of psychotic symptoms following an episode of bacteremia with high fever.

Fevered Decisions: Race, Ethics, and Clinical Vulnerability in the Malarial Treatment of Neurosyphilis, 1922-1953.

Physicians deliberately inoculated marginalized patients with malaria, using them as reservoirs to facilitate malarial fever therapy for syphilitic patients. The history presents ethical questions in an evolving historical context.

Local tumour hyperthermia as immunotherapy for metastatic cancer.

Abstract Local tumour hyperthermia for cancer treatment is currently used either for ablation purposes as an alternative to surgery or less frequently, in combination with chemotherapy and/or radiation therapy to enhance the effects of those traditional therapies. As it has become apparent that activating the immune system is crucial to successfully treat metastatic cancer, the potential of boosting anti-tumour immunity by heating tumours has become a growing area of cancer research. After reviewing the history of hyperthermia therapy for cancer and introducing methods for inducing local hyperthermia, this review describes different mechanisms by which heating tumours can elicit anti-tumour immune responses, including tumour cell damage, tumour surface molecule changes, heat shock proteins, exosomes, direct effects on immune cells, and changes in the tumour vasculature. We then go over in vivo studies that provide promising results showing that local hyperthermia therapy indeed activates various systemic anti-tumour immune responses that slow growth of untreated tumours. Finally, future research questions that will help bring the use of local hyperthermia as systemic immunotherapy closer to clinical application are discussed.

Profile of patients treated with malariotherapy in a psychiatric hospital in Porto Alegre, Brazil: a historical note / Perfil dos pacientes tratados com malarioterapia em hospital psiquiátrico de Porto Alegre: nota histórica

Introduction: Malariotherapy was a treatment to cure neurosyphilis developed in 1917 by Wagner-Jauregg, by inoculating blood infected with malaria in patients with neurosyphilis. The patient had febrile episodes that often cured him of the syphilitic infection. This treatment won the Nobel Prize in Medicine in 1927 and it was introduced in Hospital Psiquiátrico São Pedro (HPSP) in 1929. Methods: This is a descriptive retrospective cross-sectional study with collection of historical secondary data. Data were collected from a sample of 19 medical records of patients treated with malariotherapy in HPSP, in 1929 and 1930. Results: Most patients were white men aged from 25 to 40 years. The mean length of hospital stay was 1.4 year and the outcomes at this early application of malariotherapy were mostly negative (63.2% died). Discussion: The 19 cases evaluated in this study refer to the first year of application of malariotherapy in HPSP. The statistics available on the total number of dead and cured people over the 10 years this therapy was deployed suggest that the outcomes were better in the subsequent years, possibly due to improvement of technique. As a consequence of this innovative research, which had as its principle reorganizing the central nervous system by using the seizure triggered by malaria fever, other forms of shock therapies were developed, such as insulin therapy, cardiazol shock therapy, and electroconvulsive therapy (AU)

Introdução: A malarioterapia foi um tratamento para a cura da neurossífilis desenvolvido em 1917 por Wagner-Jauregg, através da inoculação de sangue contaminado pela malária em pacientes com neurossífilis. O paciente apresentava episódios febris que, muitas vezes, curavam-no da infecção sifilítica. Esse tratamento recebeu o Prêmio Nobel de Medicina em 1927 e foi introduzido no Hospital Psiquiátrico São Pedro (HPSP) em 1929. Métodos: Este é um estudo transversal retrospectivo descritivo com coleta de dados secundários históricos. Foram coletados dados de uma amostra de 19 prontuários médicos de pacientes tratados com malarioterapia no HPSP, em 1929 e 1930. Resultados: A maioria dos pacientes eram homens brancos com idades entre 25 e 40 anos. O tempo médio de internação foi de 1,4 ano e os desfechos nesse início de aplicação da malarioterapia foram majoritariamente negativos (63,2% foram a óbito). Discussão: Os 19 casos avaliados neste estudo referem-se ao primeiro ano de aplicação da malarioterapia no HPSP. As estatísticas existentes sobre o total de curados e mortos ao longo dos 10 anos de implantação dessa terapêutica sugerem que os desfechos dos anos seguintes foram melhores, possivelmente pelo aprimoramento da técnica. Como consequência dessa pesquisa inovadora, que tinha como princípio reorganizar o sistema nervoso central por meio da convulsão desencadeada pela febre da malária, outras formas de terapias de choque foram desenvolvidas, tais como a insulinoterapia, o choque por cardiazol e a eletroconvulsoterapia (AU)

Julius Wagner-Jauregg (1857-1940): Introducing fever therapy in the treatment of neurosyphilis.

For centuries, heat has been used in various ways for the cure of mental diseases. Hippocrates noted that malarial fever could have a calming effect in epileptics. Centuries later, Galen described a case of melancholy cured as a result of an attack of quartan fever. In 19th century, the eminent French psychiatrist Philippe Pinel, in his treatise on insanity referred to the beneficial effect of fever. An opinion expressed few years later by his pupil Jean-Étienne Dominique Esquirol in his treatise entitled Des maladies mentales considérées sous les rapports médical, hygiénique et médico-légal. However, in 1917, the Austrian neuro-psychiatrist Julius Wagner Jauregg pointed out the therapeutic value of malaria inoculation in the treatment of dementia paralytica. In 1927, Wagner Jauregg received for this work the Nobel Prize in Medicine, being actually the first psychiatrist to win the Nobel Prize. He studied medicine at the University of Vienna and received his doctorate in 1880. In 1889, he was appointed Professor of Psychiatry and Director of the Graz's Psychiatric Clinic, a position that he held until 1928. Working in the asylum, Wagner Jauregg noted that insane patients with general paralysis occasionally became sane after some febrile episode. After experimenting with several artificial methods (streptococci, tuberculin) to induce fever, he concluded that malaria was the most satisfactory. Actually, malaria infection was an acceptable risk for the patients, as quinine would be administered as soon as syphilis was cured. In 1917, he reported the first favorable results of his study. Patients were inoculated via intravenous injections with malaria. Some physicians were starting the administration of anti-syphilitic treatment (bismuth, salvarsan and later penicillin) after 10-12 febrile paroxysms, while others initiated the regimen the first febrile-free day after 8 malarial paroxysms. The therapeutic regimen was completed with the administration of quinine sulfate to terminate the malaria infection. It is worth mentioning that the above treatment was followed in hospital under strict monitoring of patients' vital signs and regular laboratory tests. In the following years of his discovery, artificial fever was induced by any one of the following methods: the introduction into the patient of a parasitic disease; the injection of a foreign protein; injections of chemical substances such as sulphur; electrical means such as the administration of diathermy or radiotherapy, or placing the patient in an electromagnetic field; and simple immersion of the individual in a hot bath, or placing him in a heat cabinet. Wagner Jauregg's therapy was highly admired and was used on neurosyphilis cases well onto the 1950's. However, with the introduction of penicillin in syphilis' treatment, fever therapy effectively ended. Wagner Jauregg's study led to all the methods of stress therapy used in psychiatry, as electric shock, and insulin.

Weather, geography, and vehicle-related hyperthermia in children.

Vehicle-related hyperthermia is an unfortunate tragedy that leads to the accidental deaths of children each year. This research utilizes the most extensive dataset of child vehicle-related hyperthermia deaths in the United States, including 414 deaths between 1998 and 2008. Deaths follow a seasonal pattern, with a peak in July and no deaths in December or January. Also, deaths occurred over a wide range of temperature and radiation levels and across virtually all regions, although most of them took place across the southern United States. In particular, the Phoenix, Houston, Dallas, and Las Vegas metropolitan areas had the greatest number of deaths. We utilize our vehicle hyperthermia index (vhi) to compare expected deaths versus actual deaths in a metropolitan area, based on the number of children in the area who are under the age of five and on the frequency of hot days in the area. The vhi indicates that the Memphis, West Palm Beach-Boca Raton, and Las Vegas metropolitan areas are the most dangerous places for vehicle-related hyperthermia. We conclude by discussing several recommendations with public health policy implications.