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.

2,000 Year old ß-thalassemia case in Sardinia suggests malaria was endemic by the Roman period.

OBJECTIVES: The island of Sardinia has one of the highest incidence rates of ß-thalassemia in Europe due to its long history of endemic malaria, which, according to historical records, was introduced around 2,600 years ago by the Punics and only became endemic around the Middle Ages. In particular, the cod39 mutation is responsible for more than 95% of all ß-thalassemia cases observed on the island. Debates surround the origin of the mutation. Some argue that its presence in the Western Mediterranean reflects the migration of people away from Sardinia, others that it reflects the colonization of the island by the Punics who might have carried the disease allele. The aim of this study was to investigate ß-globin mutations, including cod39, using ancient DNA (aDNA) analysis, to better understand the history and origin of ß-thalassemia and malaria in Sardinia. MATERIALS AND METHODS: PCR analysis followed by sequencing were used to investigate the presence of ß-thalassemia mutations in 19 individuals from three different Roman and Punic necropolises in Sardinia. RESULTS: The cod39 mutation was identified in one male individual buried in a necropolis from the Punic/Roman period. Further analyses have shown that his mitochondrial DNA (mtDNA) and Y-chromosome haplogroups were U5a and I2a1a1, respectively, indicating the individual was probably of Sardinian origin. CONCLUSIONS: This is the earliest documented case of ß-thalassemia in Sardinia to date. The presence of such a pathogenic mutation and its persistence until present day indicates that malaria was likely endemic on the island by the Roman period, earlier than the historical sources suggest.

Malaria was a weak selective force in ancient Europeans.

Malaria, caused by Plasmodium parasites, is thought to be one of the strongest selective forces that has shaped the genome of modern humans and was endemic in Europe until recent times. Due to its eradication around mid-twentieth century, the potential selective history of malaria in European populations is largely unknown. Here, we screen 224 ancient European genomes from the Upper Palaeolithic to the post-Roman period for 22 malaria-resistant alleles in twelve genes described in the literature. None of the most specific mutations for malaria resistance, like those at G6PD, HBB or Duffy blood group, have been detected among the available samples, while many other malaria-resistant alleles existed well before the advent of agriculture. We detected statistically significant differences between ancient and modern populations for the ATP2B4, FCGR2B and ABO genes and we found evidence of selection at IL-10 and ATP2B4 genes. However it is unclear whether malaria is the causative agent, because these genes are also involved in other immunological challenges. These results suggest that the selective force represented by malaria was relatively weak in Europe, a fact that could be associated to a recent historical introduction of the severe malaria pathogen.

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.

Paleopathology and Paleomicrobiology of Malaria.

Malaria is a disease caused by parasites of the genus Plasmodium, transmitted through the bites of female anopheles flies. Plasmodium falciparum causes severe malaria with undulating high fever (malaria tropica). Literary evidence of malarial infection dates back to the early Greek period, when Hippocrates described the typical undulating fever highly suggestive of plasmodial infection. Recent immunological and molecular analyses describe the unambiguous identification of malarial infections in several ancient Egyptian mummies and a few isolated cases in Roman and Renaissance Europe. Although the numbers of cases are low, there is evidence that the overall infection rates may have been relatively high and that this infectious disease may have had a significant impact on historical populations.

Ethnopharmacology in the fight against Plasmodium parasites and brain disorders: In memoriam of Philippe Rasoanaivo.

Prof. Philippe Rasoanaivo was a highly dedicated and brilliant scientist in the field of ethnopharmacology. He worked for the Institut Malgache de Recherches Appliquées and the University of Antananarivo, Madagascar. His research was mainly focused on the endemic medicinal and aromatic plants used by traditional healers in Madagascar against a range of parasites, with special reference to Plasmodium spp. In this Editorial, we resumed the key findings of his research activity, with special reference to the discovery of alkaloids that markedly enhance the action of chloroquine against malaria parasites.

On the history of Cinchona bark in the treatment of Malaria.

How and when the medical value of Cinchona bark was discovered is obscure, but it is said that the powder was given to a European for malaria for the first time in the 1630s. The bark was brought to Europe by Spanish missionaries and it was recommended by the cardinal Juan de Lugo. In the 1660s, the use of Cinchona bark became known in England - and in Denmark by Thomas Bartholin. It was used for the treatment of malaria, but several debates on its value continued up to the 1730s. However, successful treatment of malaria was obtained by Thomas Sydenham, Robert Tabor and Francesco Torti. Sydenham emphasized a modern view that Cinchona bark was a unique specific drug for the treatment of malaria, and the treatment was fully accepted when Torti's Therapeutice specialis appeared. In the early 18th century, botanical expeditions were arranged in search of the most valuable Cinchona species for cultivation. The content of quinine was impor- tant, and determination of quinine was realized when Pierre Pelletier and Joseph Caventou isolated the alkaloid from the bark in 1820. Dutch plantations and quinine industry dominated the market, but the supply of quinine came to an end when the Japanese occupied Indonesia in 1942, cutting off the rest of the world from the main supplies of Cinchona. Synthetic antimalarials were developed and chloroquine became the drug of choice, but the intensive use of these drugs caused drug resistance. Chloroquine-resistant strains of P. falciparum are now treated with other drugs as artemisinin and artemether.

A historical perspective on malaria control in Brazil.

Malaria has always been an important public health problem in Brazil. The early history of Brazilian malaria and its control was powered by colonisation by Europeans and the forced relocation of Africans as slaves. Internal migration brought malaria to many regions in Brazil where, given suitable Anopheles mosquito vectors, it thrived. Almost from the start, officials recognised the problem malaria presented to economic development, but early control efforts were hampered by still developing public health control and ignorance of the underlying biology and ecology of malaria. Multiple regional and national malaria control efforts have been attempted with varying success. At present, the Amazon Basin accounts for 99% of Brazil's reported malaria cases with regional increases in incidence often associated with large scale public works or migration. Here, we provide an exhaustive summary of primary literature in English, Spanish and Portuguese regarding Brazilian malaria control. Our goal was not to interpret the history of Brazilian malaria control from a particular political or theoretical perspective, but rather to provide a straightforward, chronological narrative of the events that have transpired in Brazil over the past 200 years and identify common themes.

A historical perspective on malaria control in Brazil

Malaria has always been an important public health problem in Brazil. The early history of Brazilian malaria and its control was powered by colonisation by Europeans and the forced relocation of Africans as slaves. Internal migration brought malaria to many regions in Brazil where, given suitableAnopheles mosquito vectors, it thrived. Almost from the start, officials recognised the problem malaria presented to economic development, but early control efforts were hampered by still developing public health control and ignorance of the underlying biology and ecology of malaria. Multiple regional and national malaria control efforts have been attempted with varying success. At present, the Amazon Basin accounts for 99% of Brazil’s reported malaria cases with regional increases in incidence often associated with large scale public works or migration. Here, we provide an exhaustive summary of primary literature in English, Spanish and Portuguese regarding Brazilian malaria control. Our goal was not to interpret the history of Brazilian malaria control from a particular political or theoretical perspective, but rather to provide a straightforward, chronological narrative of the events that have transpired in Brazil over the past 200 years and identify common themes.

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.

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)

Science in the service of colonial agro-industrialism: the case of cinchona cultivation in the Dutch and British East Indies, 1852-1900.

The isolation of quinine from cinchona bark in 1820 opened new possibilities for the mass-production and consumption of a popular medicine that was suitable for the treatment of intermittent (malarial) fevers and other diseases. As the 19th century European empires expanded in Africa and Asia, control of tropical diseases such as malaria was seen as crucial. Consequently, quinine and cinchona became a pivotal tool of British, French, German and Dutch empire-builders. This comparative study shows how the interplay between science, industry and government resulted in different historical trajectories for cinchona and quinine in the Dutch and British Empires during the second half of the 19th century. We argue that in the Dutch case the vectors of assemblage that provided the institutional and physical framework for communication, exchange and control represent an early example of commodification of colonial science. Furthermore, both historical trajectories show how the employment of the laboratory as a new device materialised within the colonial context of agricultural and industrial production of raw materials (cinchona bark), semi-finished product (quinine sulphate) and plant-based medicines like quinine. Hence, illustrating the 19th century transition from 'colonial botany' and 'green imperialism' to what we conceptualise as 'colonial agro-industrialism'.

An Empire's Extract: Chemical Manipulations of Cinchona Bark in the Eighteenth-Century Spanish Atlantic World.

In 1790, the Spanish Crown sent a "botanist-chemist" to South America to implement production of a chemical extract made from cinchona bark, a botanical medicament from the Andes used throughout the Atlantic World to treat malarial fevers. Even though the botanist-chemist's efforts to produce the extract failed, this episode offers important insight into the role of chemistry in the early modern Atlantic World. Well before the Spanish Crown tried to make it a tool of empire, chemistry provided a vital set of techniques that circulated among a variety of healers, who used such techniques to make botanical medicaments useful and intelligible in new ways.