A twenty-first century perspective on concepts of modern epidemiology in Ignaz Philipp Semmelweis' work on puerperal sepsis.

We aimed to review Semmelweis's complete work on puerperal sepsis mortality in maternity wards in relation to exposure to cadavers and chlorine handwashing and other factors from the perspective of modern epidemiological methods. We reviewed Semmelweis' complete work and data as published by von Györy 1905 according to current standards. We paid particular attention to Semmelweis's definition of mortality in and of itself, to concepts of modern epidemiology that were already recognizable in Semmelweis's work, and to bias sources. We did several quantitative bias analyses to address selection bias and information bias from outcome measurement error. Semmelweis addressed biases that have become known to modern epidemiology, such as confounding, selection bias and bias from outcome misclassification. Our bias analysis shows that differential loss to follow-up is an unlikely explanation for his results. Bias due to outcome misclassification would only be relevant if misclassification differed between time periods. Confounding by health status was likely but could not be quantitatively addressed. Semmelweis was aware that cause-specific mortality is a function of incidence and prognosis. He reasoned in potential outcome terms to estimate the reduced number of deaths from an intervention. He advanced a hypothesis of clinic overcrowding as a risk factor for puerperal sepsis mortality that turns out to be wrong. Semmelweis' data provide a great pool for illustrating the logic of scientific discovery by use of the numerical method. The explanatory power of his work was strong and Semmelweis was able to refute several previous causal explanations.

What can the early infection preventing pioneers teach infection prevention and control teams today?

BACKGROUND: Puerperal fever and erysipelas were common Streptococcal infections of the 18th and 19th centuries which caused extensive nosocomial outbreaks. With dramatic clinical presentations and high-mortality, physicians struggled to understand and prevent them. Three infection prevention and control (IPC) pioneers (Gordon, Holmes and Semmelweis) in the pre-antibiotic and pre-epidemiology era made significant discoveries. Although much has been written of their breakthroughs, this has been selective and at times misinterpreted. METHODS: The primary sources of the three IPC pioneers (1 translation) were reviewed to present 3 narratives of their discoveries. An interpretation of the pioneers' discoveries in the current context is provided. RESULTS: The IPC pioneers' achievements are much wider than acknowledged in extant hand hygiene guidance - in relation to the role of indirect contact transmission (environment and equipment), e.g. Semmelweis considered the primary measure to prevent infection to be the avoidance of contamination - not hand hygiene. CONCLUSIONS: The pioneers provided strong evidence of both direct and indirect transmission to significant 18th -19th century infections. They make a strong case for environment and equipment decontamination and cleanliness alongside decontaminating hands.

Vindicating a traduced genius: Ignaz Philipp Semmelweis (1818-1865).

Anglophone narratives of Semmelweis's discovery of the cause and prophylaxis of childbed (puerperal) fever are based on a deficient historical record because important information about what happened to Semmelweis in Vienna, Austria, is contained in primary documents that had never been translated into English until very recently. The gaps in these narratives have been filled with invented facts and causal attributions that traduce Semmelweis by berating his character, education, and writing proficiency to hold him solely responsible for the rejection of his theory by most of his contemporaries and to explain the most puzzling aspect of his life: why he did not publish the results of his groundbreaking research in a medical journal for 11 years. This article presents the historical evidence contained in these primary documents that were missing from previous narratives and that provide very rational and understandable explanations for Semmelweis's actions. It also presents evidence that flatly contradicts the claims that have been made about Semmelweis's character, education, and writing skills and offers a more veridical portrayal of what happened to Semmelweis in Vienna that caused him to leave the city and delay publishing his results.

[Puerperal insanity:a comparative reading of Argentina and Colombia, 1880-1950]. / Las locuras puerperales: una lectura comparada entre Argentina y Colombia, 1880-1950.

Our goal is to understand the appearance and spread of forms of puerperal insanity in Argentina and Colombia in the late nineteenth and early twentieth century, as well as their decline or disappearance around the 1940s. This is a historical and hermeneutical study, which uses the concepts of "field of visibility" and "ecological niche" for a transitory disease. There was no correlation between pregnancy, childbirth and puerperium and the state of delirium that led to commitment, which was attributed to predisposing factors; furthermore, forms of puerperal insanity were nosographically distinct due to their unique etiopathogeneses. As clinical cases of puerperal insanity started to emerge, the disciplinary field of obstetrics converged with psychiatry, with the former exerting more weight.

El objetivo es comprender la aparición y propagación de locuras puerperales en Argentina y Colombia, a finales del siglo XIX y principios del XX, así como su decadencia o desvanecimiento hacia la década de 1940-1950. Investigación histórico-hermenéutica, según los conceptos de "campo de visibilidad" y "nicho ecológico" de una enfermedad transitoria. No existió correlación entre embarazo, parto y puerperio con el estado delirante que motivaba la internación, atribuido a factores predisponentes y, asimismo, tuvieron una autonomía nosográfica en virtud de etiopatogenias singulares. Al tiempo que empezó a emerger el tipo clínico locura puerperal, se entrecruzaron el campo disciplinar de la obstetricia con el alienismo, con una mayor preponderancia del primero.

Las locuras puerperales: una lectura comparada entre Argentina y Colombia, 1880-1950 / Puerperal insanity: a comparative reading of Argentina and Colombia, 1880-1950

Resumen El objetivo es comprender la aparición y propagación de locuras puerperales en Argentina y Colombia, a finales del siglo XIX y principios del XX, así como su decadencia o desvanecimiento hacia la década de 1940-1950. Investigación histórico-hermenéutica, según los conceptos de "campo de visibilidad" y "nicho ecológico" de una enfermedad transitoria. No existió correlación entre embarazo, parto y puerperio con el estado delirante que motivaba la internación, atribuido a factores predisponentes y, asimismo, tuvieron una autonomía nosográfica en virtud de etiopatogenias singulares. Al tiempo que empezó a emerger el tipo clínico locura puerperal, se entrecruzaron el campo disciplinar de la obstetricia con el alienismo, con una mayor preponderancia del primero.

Abstract Our goal is to understand the appearance and spread of forms of puerperal insanity in Argentina and Colombia in the late nineteenth and early twentieth century, as well as their decline or disappearance around the 1940s. This is a historical and hermeneutical study, which uses the concepts of "field of visibility" and "ecological niche" for a transitory disease. There was no correlation between pregnancy, childbirth and puerperium and the state of delirium that led to commitment, which was attributed to predisposing factors; furthermore, forms of puerperal insanity were nosographically distinct due to their unique etiopathogeneses. As clinical cases of puerperal insanity started to emerge, the disciplinary field of obstetrics converged with psychiatry, with the former exerting more weight.

Rediscovering Ignaz Philipp Semmelweis (1818-1865).

Ignaz Philipp Semmelweis was a Hungarian obstetrician who discovered the cause of puerperal or childbed fever (CBF) in 1847 when he was a 29-year-old Chief Resident ("first assistant") in the first clinic of the lying-in division of the Vienna General Hospital. Childbed fever was then the leading cause of maternal mortality, and so ravaged lying-in hospitals that they often had to be closed. The maternal mortality rate (MMR) from CBF at the first clinic where Semmelweis worked, and where only medical students were taught, was 3 times greater than at the second clinic, where only midwives were taught, and Semmelweis was determined to find out why. Semmelweis concluded that none of the purported causes of CBF could explain the difference in MMR between the 2 clinics, as they all affected both clinics equally. The clue to the real cause came after Semmelweis' beloved professor, Jacob Kolletschka, died after a student accidentally pricked Kolletscka's finger during an autopsy. Semmelweis reviewed Kolletschka's autopsy report, and noted that the findings were identical to those in mothers dying of CBF. He then made 2 groundbreaking inferences: that Kolletschka must have died of the same disease as mothers dying of CBF, and that the cause of CBF must be the same as the cause of Kolletschka's death, because if the 2 diseases were the same, they must have the same cause. Semmelweis quickly realized why the MMR from CBF was higher on the first clinic: medical students, who assisted at autopsies, were transferring the causative agent from cadavers to the birth canal of mothers in labor with their hands, and he soon discovered that it could also be transferred from living persons with purulent infections. Bacteria had not yet been discovered to cause infections, and Semmelweis called the agent "decaying animal organic matter." He implemented chlorine hand disinfection to remove this organic matter from the hands of the attendants, as soap and water alone had been ineffective. Hand disinfection reduced the MMR from CBF 3- to 10-fold, yet most leading obstetricians rejected Semmelweis' doctrine because it conflicted with all extant theories of the cause of CBF. His work was also used in the fight raging over academic freedom in the University of Vienna Medical School, which turned Semmelweis chief against him, and forced Semmelweis to return to Budapest, where he was equally successful in reducing MMR from CBF. But Semmelweis never received the recognition that his groundbreaking work deserved, and died an ignominious death in 1865 at the age of 47 in an asylum, where he was beaten by his attendants and died of his injuries. Fifteen years later, his work was validated by the adoption of the germ theory, and honors were belatedly showered on Semmelweis from all over the world; but over the last 40 years, a myth has been created that has tarnished Semmelweis' reputation by blaming the rejection of his work on Semmelweis' character flaws. This myth is shown to be a genre of reality fiction that is inconsistent with historical facts.

Birthing life and death: women's reproductive health in early twentieth-century Rio de Janeiro / Vida e morte no parto: saúde reprodutiva das mulheres no Rio de Janeiro do início do século XX

Abstract This article explores women's reproductive health in early twentieth-century Rio de Janeiro, showing that elevated and sustained stillbirth and maternal mortality rates marked women's reproductive years. Syphilis and obstetric complications during childbirth were the main causes of stillbirths, while puerperal fever led maternal death rates. Utilizing traditional sources such as medical dissertations and lesser-used sources including criminal investigations, this article argues that despite official efforts to medicalize childbirth and increase access to clinical healthcare, no real improvements were made to women's reproductive health in the first half of the twentieth century. This, of course, did not make pregnancy and childbirth any easier for the women who embodied these statistics in their reproductive lives.

Resumo O artigo aborda a saúde reprodutiva das mulheres no Rio de Janeiro do início do século XX, mostrando que taxas elevadas de mortalidade materna e de contínua natimortalidade marcavam os anos reprodutivos das mulheres. As principais causas de natimortalidade eram sífilis e complicações obstétricas, enquanto febre puerperal encabeçava as taxas de morte materna. Utilizando fontes tradicionais como teses doutorais e fontes como investigações criminais, o artigo discute que, apesar dos esforços oficiais para medicalizar o parto e aumentar o acesso aos serviços de saúde, nenhuma melhoria real foi feita na saúde reprodutiva das mulheres na primeira metade do século XX. Isso, certamente, não facilitou a gravidez e o parto das mulheres que compunham as estatísticas em suas vidas reprodutivas.

[200th birth anniversary of Ignatius Philipp Semmelweis] / Uz 200. obljetnicu rodenja Ignaza Philippa Semmelweisa

Ignaz Phillip Semmelweis's significance for the history of medicine lies in his discovery of the cause of puerperal fever. He discovered it during his work at the First Obstetrics Clinic of the Vienna's Allgemeines Krankenhaus. Since the mentioned Clinic, led by the doctors, had much higher mortality rates of the child-bearing women than the Second Obstetrics Clinic, led by the midwives, he wanted to determine the causes of such a state. He came to the conclusion that puerperal sepsis was transmitted by the doctors and medical students, who after performing the anatomical sections started to perform the births with their hands beforehand washed only with soap. Semmelweis instead proposed a mandatory hand washing in a potassium-hypochlorite solution thus making the mortality at the First equivalent to the mortality at the Second Obstetrics Clinic. Despite this, his discovery was rejected by the established medical circuits.

[Semmelweis - a contemplating human. Scientific historical lessons]. / Semmelweis ­ egy gondolkodó ember. Tudománytörténeti tanulságok.

In this article we examine why Semmelweis's seemingly simple, logical and practical discovery was categorically dismissed by the majority of his contemporaries, and why even many years after his death it was accepted with such reservation. We invoke wherever possible Semmelweis's own words citing from the series of articles appearing in the 'Orvosi Hetilap' [Hungarian Medical Weekly Journal] published in 1858 in Hungary, and also from the German language summary of the Journal published in 1860. We came to the conclusion that although Semmelweis did everything in his power to show the causal relationship between the development of puerperal fever (childbed fever) and some infectious substance on the hands of examining doctors and medical students, this was not convincing enough. The predominant theory at the time held that infection was caused by miasma transmitted in the air and therefore stubbornly precluded any notion of infectious matter physically transmitted on unclean hands. We also concluded that the causal sequence observed by Semmelweis was missing an essential empirical element: visual proof of the infectious agent he correctly postulated as physically transmitted. Visually demonstrating the presence of the infectious agent by means of a microscope would have made his case. This finally did occur but only two years after Semmelweis's death. Had the renowned Hungarian obstetrician realized the significance of taking advantage of the opportunity afforded by Dávid Gruby who was conducting experiments in the same town, a more convincing argument could have been made for his theory. In the 1840s and 1850s, Dávid Gruby was experimenting with various microscopic techniques and their application with success in Vienna before continuing his work in France. Gruby's work, especially that of microscopic observations of tissues, received international acceptance. Therefore, the involvement of Gruby and his work with microscopes to support Semmelweis's observations would most probably have forestalled much of the criticism and rejection his theory was initially awarded (among which perhaps Virchow's rejection proved the most damaging). Had Semmelweis utilized microscopic techniques, he would have been celebrated among the first to discover bacterial pathogens, contributing to the development of the currently predominant germ theory. Failure to utilize the microscope was the root cause leading to the tragedy of Semmelweis's rejection by the medical establishment of the time. Despite the increasing numbers of scientists utilizing the microscope at the University of Pest, offered to corroborate his daims with microscopic observations. Efforts have been made have since been to rehabilitate him as the key figure who not only discovered the method of transmission of infectious disease, but also implemented measures of prevention. Elevating him among the ranks of the ten greatest doctors who ever lived is certainly recognition due, but sadly denied to him in his lifetime. Orv Hetil. 2018; 159(26): 1055-1064.

[The savior of mothers and newborns, whom we shall always be proud of: Ignác Semmelweis (1818-1865). One who defeated the disease, yet could not convince the people, Doctor of Medical Sciences and Surgery, Master of Obstetrics, Professor of Theoretical and Practical Obstetrics at the Pest Royal Hungarian University of Sciences]. / Az anyák és az újszülöttek megmentoje, akire mindig büszkék leszünk: Semmelweis Ignác (1818­1865). Aki legyozte a kórt, de nem gyozte meg a kort, az orvostudományok és a sebészet doktora, szülészmester, a Pesti Királyi Magyar Tudományegyetemen az elméleti és gyakorlati szülészet nyilvános, rendes tanára.

Semmelweis finally achieved results from his persistent research work. Those being the scientific analysis of clinical statistical data and his animal experiments, which recognized the dreadful disease of puerperal fever and its prevention. "He not only discovered the real cause of puerperal fever but he also created antiseptic prophylaxis, which he introduced in obstetrics and laid the foundations of modern surgery (asepsis). The theory and practice of asepsis stemmed from the discovery of the etiology of puerperal fever and therefore originating from the genius idea of Semmelweis. The discoveries of bacteriology by Lister, Pasteur and Koch only provided a scientific proof of the intuitive statements of Semmelweis." Semmelweis was a pioneer of clinical etiological research whose findings were aggressively disapproved by his colleagues due to earlier medical misunderstandings. Semmelweis is given due respect by posterity as a remuneration, to all the bitterness that he had suffered throughout his life. Semmelweis is considered the savior of mothers and infants. The Hungarian nation is very proud of him as he is one of our models whose oeuvre is acknowledged not only in Hungary but throughout the world. The message of his short, tragic yet effective life is eternal. The figure of Ignác Semmelweis is depicted as a statue and is placed in Chicago among the statues of the most innovative doctors and health care professionals of the world. The statue of Semmelweis is next to the statues of Louis Pasteur and Wilhelm Conrad Röntgen. "Semmelweis reflex" is a new expression which appeared and spread in English speaking countries. The word does not relate to a medical phenomenon but describes a social phenomenon when experts or the whole society automatically rejects discoveries and new recognitions without examination or justification. This phenomenon frequently occurs, even in our times. Orv Hetil. 2018; 159(26): 1041-1054.

[Ignác Semmelweis and the Hungarian Medical Weekly Journal]. / Semmelweis Ignác és az Orvosi Hetilap.

Ignác Semmelweis did not publish his discovery in Vienna - i.e., that the puerperal fever may be prevented by careful washing of the hand in chlorine solution (asepsis) - for ten years. The Medical Weekly started its publications edited by Lajos Markusovszky in Pest in 1857. Semmelweis as a professor of theoretical and practical obstetrics at the University of Pest published a study about puerperal fever in the first volume, and Hungarian physicians became familiar with Semmelweis' opinion from this medical journal. Semmelweis was not only an author of the Medical Weekly, but he also edited a supplement of the Medical Weekly entitled Gynaecology and Paediatry. The Medical Weekly published regular accounts of the work of the clinic written by lecturers of Semmelweis and articles describing the most interesting cases of the clinic. Orv Hetil. 2018; 159(26): 1065-1070.

Birthing life and death: women's reproductive health in early twentieth-century Rio de Janeiro.

This article explores women's reproductive health in early twentieth-century Rio de Janeiro, showing that elevated and sustained stillbirth and maternal mortality rates marked women's reproductive years. Syphilis and obstetric complications during childbirth were the main causes of stillbirths, while puerperal fever led maternal death rates. Utilizing traditional sources such as medical dissertations and lesser-used sources including criminal investigations, this article argues that despite official efforts to medicalize childbirth and increase access to clinical healthcare, no real improvements were made to women's reproductive health in the first half of the twentieth century. This, of course, did not make pregnancy and childbirth any easier for the women who embodied these statistics in their reproductive lives.

[Study on the 19(th) century puerperal fever epidemic: Semmelweis-an often neglected pioneer epidemiologist].

Puerperal fever was a major cause of maternal death in Europe in the 19(th) century. Many efforts were made to investigate the cause of the epidemic but failed. In 1846, Semmelweis, a young obstetrician in Vienna General Hospital, started his historical investigation. His breakthrough was largely due to his doctor friend's accidental injury during autopsy and his consequential death. Semmelweis found the pathological findings in his friend's post mortem examination were very similar to puerperal fever. He postulated his friend's death might be caused by "cadaverous particles" from cadavers and further inferred that puerperal fever might also be caused by the cadaverous particles that doctors brought to the delivering women after autopsy classes. He advocated hand-washing with chlorinated lime solution to wash off those particles, which rapidly reduced the maternal mortality in his department by 80% (from 10.65% to 1.98%). However, what his unprecedented work brought him was only denial, mockery and career setback rather than support, honor and compliments. Under substantial psychological pressure, he had a mental breakdown and died in a psychiatry asylum at the age of 47. He was a pioneer in epidemiological investigations before John Snow and in aseptic techniques before Joseph Lister, but his work is still often neglected.