Lethal Infectious Diseases as Inborn Errors of Immunity: Toward a Synthesis of the Germ and Genetic Theories.

It was first demonstrated in the late nineteenth century that human deaths from fever were typically due to infections. As the germ theory gained ground, it replaced the old, unproven theory that deaths from fever reflected a weak personal or even familial constitution. A new enigma emerged at the turn of the twentieth century, when it became apparent that only a small proportion of infected individuals die from primary infections with almost any given microbe. Classical genetics studies gradually revealed that severe infectious diseases could be driven by human genetic predisposition. This idea gained ground with the support of molecular genetics, in three successive, overlapping steps. First, many rare inborn errors of immunity were shown, from 1985 onward, to underlie multiple, recurrent infections with Mendelian inheritance. Second, a handful of rare and familial infections, also segregating as Mendelian traits but striking humans resistant to other infections, were deciphered molecularly beginning in 1996. Third, from 2007 onward, a growing number of rare or common sporadicinfections were shown to result from monogenic, but not Mendelian, inborn errors. A synthesis of the hitherto mutually exclusive germ and genetic theories is now in view.

A 21st century view of infection control in everyday settings: Moving from the Germ Theory of Disease to the Microbial Theory of Health.

BACKGROUND: The growing understanding of the importance of a healthy microbiome is challenging traditional thinking that resulted in the general acceptance of the Germ Theory of Disease. We propose a more encompassing Microbial Theory of Health that will have implications for the way that we address our relationship with microbes, including hygiene policy and community-based infection control practices. METHODS: This paper considers theories over the last 30 years that have impacted hygiene policy and consumer practice, from the Germ Theory of Disease and the Hygiene Hypothesis, to the Microbial Theory of Health, including the concept of Bidirectional Hygiene. Here we present a high-level review of the literature on pathogen transmission and the cycle of infection in the home and everyday settings. RESULTS: Targeted hygiene is an evidence-based hygiene policy that is employed to prevent transmission of pathogens and the transmission of infectious diseases through targeting only sites, surfaces, and practices that are considered high risk for pathogen transmission. Targeted hygiene also discourages the indiscriminate use of broad-spectrum microbicides for lower-risk activities and surfaces. CONCLUSIONS: The Microbial Theory of Health, including age-appropriate and health-appropriate hygiene practices for home and everyday life, should usher in a new era in which pathogen reduction can be accomplished without indiscriminate elimination of potentially beneficial microbes from the human and environmental microbiomes.

Spontaneous Generation and an Eighteenth Century Italian Rabbi-Physician.

Spontaneous generation is usually stated to have been laid to rest by Louis Pasteur with his swan-necked flask experiments. However, a century and a half earlier an Italian physician-Rabbi, Isaac Lampronti, was so convinced of the falsity of spontaneous generation that he was willing to overturn Jewish legal precedent.

From germ theory to germ therapy.

Germ theory of disease and Koch's postulates has been governing our understanding of the role of microbes in human health since 19th century. The discovery of Helicobacter pylori (H. pylori) and H. pylori associated diseases has typically represented the concept and framework of Koch's postulates. Eradication of H. pylori to prevent peptic ulcers recurrence and gastric cancer is the triumph of this microbiology paradigm. Advances of next generation sequencing provide great insight into the unculturable microbes and show trillions of microbes have evolved with human beings. Research into the microbiome-the microbial communities (microbiota) and the host environment that they inhabit-has changed our understanding about microbes in human health and disease. The gut microbiota, the largest reservoir of the microbiome in human, plays a critical role in our catabolic-metabolism and immunity. This review will show the changes of the view of microbes on human health. We will briefly discuss dysbiosis, the disruption of symbiotic relationship between the host and microbiota, and the associated diseases. This leads to an idea to manipulate the microbiota, either by restoring missing functions or by eliminating harmful functions, to prevent or treat a variety of diseases. Current evidences of two common germ therapies, fecal microbiota transplantation and probiotics, in treating diseases will be reviewed.

Universal etiology, multifactorial diseases and the constitutive model of disease classification.

Infectious diseases are often said to have a universal etiology, while chronic and noncommunicable diseases are said to be multifactorial in their etiology. It has been argued that the universal etiology of an infectious disease results from its classification using a monocausal disease model. In this article, I will reconstruct the monocausal model and argue that modern 'multifactorial diseases' are not monocausal by definition. 'Multifactorial diseases' are instead defined according to a constitutive disease model. On closer analysis, infectious diseases are also defined using the constitutive model rather than the monocausal model. As a result, our classification models alone cannot explain why infectious diseases have a universal etiology while chronic and noncommunicable diseases lack one. The explanation is instead provided by the Nineteenth Century germ theorists.

Infection, contagion and causality in Colonial Britain: the 1889-90 influenza pandemic and the British Medical Journal.

The influenza pandemic of 1889 was the first truly global flu outbreak in scope. Characterised by high morbidity and low mortality, it spread rapidly across Europe and the rest of the world along trading routes. It reached mainland Britain in December 1889. The responses of medical practitioners in Britain and the British colonies to the pandemic were heavily featured in the British Medical Journal and reveal a confusing picture around causality, contagion and infection. Cases from the colonies (Cape Town, India, Australia, Samoan Islands, Hong Kong) as presented in the journal are explored in an attempt to reconstruct the mainstream medical belief of the time. The evidence sadly shows a lack of confidence in contagionism, almost complete absence of monocausalism and a vague picture of the epidemic constitution. Original case studies from colonial medical officers as well as editorials triggered a debate in the pages of the BMJ. In this context, the journal succeeded in playing a key role in recording the first thoroughly documented attack of influenza. In a world that was only learning to be interconnected, the BMJ became the point of reference for the British medical establishment, which ranged from London to Scotland and from Africa and India to Oceania.

Reorganizing Hospital Space: The 1894 Plague Epidemic in Hong Kong and the Germ Theory.

This paper examined whether the preventive measures taken by the Hong Kong's colonial authorities were legitimate during the 1894 Hong Kong plague epidemic, and illuminated the correlation between the plague epidemic and hospital space in Hong Kong in the late 19th century. The quarantine measures taken by the colonial authorities were neither a clear-cut victory for Western medicine nor for a rational quarantine based on scientific medical knowledge. Hong Kong's medical officials based on the miasma theory, and focused only on house-to-house inspections and forced quarantine or isolation, without encouraging people to wear masks and without conducting disinfection. Even after Hong Kong plague spread, the Hong Kong's colonial authorities were not interested in what plague bacilli were, but in where they were to be found and how to prevent and control an outbreak of the disease. The germ theory brought significant changes to the disease classification system. Until the 1890s, Hong Kong's colonial authority had classified cause of death mainly on the basis of symptoms, infectious diseases, parts of the body and diseases of systems. Microbiological analysis of the cause of death in Hong Kong was started by Hunter, a bacteriologist, in 1902. He used bacteriological tests with a microscope to analyze the cause of death. New disease recognition and medical recognition brought large changes to hospital space as well. In particular, from the 1880s to the early 1900s, Western medical circles witnessed shifts from miasma theory to the germ theory, thereby influencing Hong Kong's hospital spaces. As the germ theory took ground in Hong Kong in 1894, the bacteriological laboratory and isolation ward became inevitable facilities, and hospital space were reorganized accordingly. However, the colonial authorities and local elites' strategy was different. As a government bacteriologist, Hunter established a central facility to unify several laboratories and to manage urban space from ouside the hospital. On the contrary, the Tungwah Hospital tried to transform hospital space with isolation ward and Receiving Ward System as the eclectic form of Chinese and Western medicine. The 1894 Hong Kong plague promoted the introduction of germ theory and the reorganization of hospital space.

Enteric immunity, the gut microbiome, and sepsis: Rethinking the germ theory of disease.

Sepsis is a poorly understood syndrome of systemic inflammation responsible for hundreds of thousands of deaths every year. The integrity of the gut epithelium and competence of adaptive immune responses are notoriously compromised during sepsis, and the prevalent assumption in the scientific and medical community is that intestinal commensals have a detrimental role in the systemic inflammation and susceptibility to nosocomial infections seen in critically ill, septic patients. However, breakthroughs in the last decade provide strong credence to the idea that our mucosal microbiome plays an essential role in adaptive immunity, where a human host and its prokaryotic colonists seem to exist in a carefully negotiated armistice with compromises and benefits that go both ways. In this review, we re-examine the notion that intestinal contents are the driving force of critical illness. An overview of the interaction between the microbiome and the immune system is provided, with a special focus on the impact of commensals in priming and the careful balance between normal intestinal flora and pathogenic organisms residing in the gut microbiome. Based on the data in hand, we hypothesize that sepsis induces imbalances in microbial populations residing in the gut, along with compromises in epithelial integrity. As a result, normal antigen sampling becomes impaired, and proliferative cues are intermixed with inhibitory signals. This situates the microbiome, the gut, and its complex immune network of cells and bacteria, at the center of aberrant immune responses during and after sepsis.

O micróbio protagonista: notas sobre a divulgação da bacteriologia na Gazeta Médica da Bahia, século XIX / The protagonist microbe: notes on the communication of bacteriology in the Gazeta Médica da Bahia journal, nineteenth century

Resumo A teoria dos germes, decorrente, em especial, dos trabalhos de Louis Pasteur e Robert Koch, fez estremecer as bases do saber médico a partir da segunda metade do período oitocentista e promoveu uma revolução na “arte de curar”. A busca por micróbios específicos para as doenças norteou as investigações de pesquisadores convertidos aos dogmas pasteurianos. Este trabalho procura mostrar, em linhas gerais, o papel desempenhado pela Gazeta Médica da Bahia no processo de divulgação da bacteriologia junto às comunidades médicas baiana e nacional. O artigo apresenta alguns trabalhos e reflexões de colaboradores do periódico e destaca algumas controvérsias que ajudaram a traçar um panorama da difusão da teoria dos germes pelo Brasil ao longo do século XIX.

Abstract Germ theory, derived particularly from the work of Louis Pasteur and Robert Koch, shook the foundations of medical knowledge in the second half of the nineteenth century and triggered a revolution in the “art of healing.” The search for specific microbes for diseases guided the investigations of the researchers converted to the Pasteurian tenets. This paper aims to show what role the Gazeta Médica da Bahia journal played in spreading knowledge about bacteriology to the medical communities in Bahia and throughout Brazil. Some works and reflections by the newspaper’s authors at the time are presented, as are some of the controversies that help depict the way germ theory was divulged in Brazil throughout the nineteenth century.

[The protagonist microbe: notes on the communication of bacteriology in the Gazeta Médica da Bahia journal, nineteenth century]. / O micróbio protagonista: notas sobre a divulgação da bacteriologia na Gazeta Médica da Bahia, século XIX.

Germ theory, derived particularly from the work of Louis Pasteur and Robert Koch, shook the foundations of medical knowledge in the second half of the nineteenth century and triggered a revolution in the "art of healing." The search for specific microbes for diseases guided the investigations of the researchers converted to the Pasteurian tenets. This paper aims to show what role the Gazeta Médica da Bahia journal played in spreading knowledge about bacteriology to the medical communities in Bahia and throughout Brazil. Some works and reflections by the newspaper's authors at the time are presented, as are some of the controversies that help depict the way germ theory was divulged in Brazil throughout the nineteenth century.

Felix Platter and a historical perspective of the meningioma.

INTRODUCTION: Felix Platter is one of the pioneer anatomists and physicians of the 16th century who described various human diseases including meningioma. In this historical article, we present the details of Platter's life and his pioneering work on meningioma. FIRST CASE OF MENINGIOMA: In 1614, Dr. Platter described the first case of meningioma. He described the tumor as a round, fleshy mass shaped like an acorn and as large as a medium-sized apple, and full of holes. The tumor was covered with its own membrane, had no connection with the matters of the brain, and left behind a cavity after removal. This first clear description of an intracranial tumor is most consistent with encapsulated meningioma. The succeeding scholar, Harvey Cushing, coined the term "meningioma" for this tumor; neurosurgeons today describe the tumor as "parasagittal or falcine meningioma." OTHER CONTRIBUTIONS: In addition to his contribution to meningioma study, Dr. Platter was also the first to describe Dupuytren's disease, hypertrophy of the thalamus, and the retina as the sensory organ of the eye. He contributed to the germ theory of disease and gave substantial accounts of mental illnesses, gynecological disorders, and certain dermatological conditions. PUBLICATIONS: Dr. Platter published numerous accounts on various diseases. In 1614 he reported the case of meningioma in the book entitled "Platerus Observations in Hominis". Additionally, Dr. Platter published his work, 'Praxeos Medicae,' which contains his most important contribution on psychiatry and his classification of psychiatric diseases. CONCLUSION: Because of his many contributions to neuroscience, particularly his identification of meningioma, Dr. Platter should be highly credited as a pioneer in the field of neurosurgery.

On putative periodontal pathogens: an epidemiological perspective.

The current understanding on the role of microbiology on periodontitis causation is reviewed. An appraisal of the literature reveals several issues that have limited the attempts to investigate candidate periodontal pathogens as causes of periodontitis and confirms that only limited epidemiological evidence is available. Several aspects of the contemporary understanding on causal inference are discussed with examples for periodontitis.

Disinfection in the laboratory: theory and practice in disinfection policy in late C19th and early C20th England.

This article examines the relationship between theory and practice in nineteenth century English public health disinfection practice. Disinfection undertaken by local authorities and practised on objects, spaces and people became an increasingly common public health practice in the last quarter of the nineteenth century, and was part of a newly developed public health system of 'stamping out' disease as described by Hardy. Despite disinfection's key role in public health policy, it has thus far not received significant investigation or historiographical attending. This article explores the development of disinfection policy at local level, highlighting that despite commentators assumptions that increasingly exacting standards of disinfection required professional oversight rather than that of the 'amateur' public, there was a significant gap between laboratory based knowledge and evidence derived from practical experience. Laboratory conditions could not replicate those found in day-to-day disinfection, and there were myriad debates about how to create a mutually understandable scientific standard for testing. Despite increasing efforts to bring local disinfection in line with new ideas promulgated by central government and disinfection researchers, the mismatches between the two meant that there was greater divergence. This tension lay at the heart of the changes in disinfection theory and practice in the second half of the nineteenth century, and illustrate the complexities of the impact of germ theory on public health policy.

Análisis bacteriológico de superficies inertes / Bacteriological analysis of inert surfaces

Objetivo: analizar microrganismos presentes en las superficies inertes, que representen un riesgo para la salud de los estudiantes. Métodos: se realizó un estudio observacional, exploratorio y transversal realizado en el periodo febrero- julio de 2012. Se efectuó en un muestreo aleatorio utilizando el método del hisopo y se obtuvieron 72 muestras. Las unidades de análisis fueron mesas, microscopios y charolas por considerarse superficies de mayor contacto con alumnos. Resultados: se encontraron hongos en el 100 por ciento de los cultivos realizados y bacterias en el 66 por ciento. De estas, el 25 por ciento (12) correspondieron a bacterias de flora normal, el 62,5 por ciento (30) a bacterias oportunistas y 12,5 por ciento (6) a bacterias patógenas. Conclusión: las mesas y los microscopios de los laboratorios de enseñanza se encuentran contaminados por hongos y bacterias como Salmonella paratyphi A y Salmonella sp que constituyen un riesgo de infección para los estudiantes que realizan prácticas educativas(AU)

Objective: analyze microorganisms present on inert surfaces which represent a health hazard for students. Methods: an observational cross-sectional exploratory study was conducted from February to July 2012. Random sampling was performed using the swab method. Seventy-two samples were obtained. The study surfaces were tables, microscopes and trays, i.e. the surfaces most commonly touched by students. Results: fungi were found in 100 percent of the cultures. Bacteria were found in 66%. Of the latter, 25 percent (12) were normal flora bacteria, 62.5 percent (30) were opportunistic, and 12.5 (6) were pathogenic. Conclusion: tables and microscopes in teaching laboratories were contaminated with fungi and bacteria such as Salmonella paratyphi A and Salmonella sp., which constitutes an infection hazard for students doing laboratory practice(AU)

From germ theory to germ therapy: skin microbiota, chronic wounds, and probiotics.

BACKGROUND: Microorganisms living throughout the body comprise the human "microbiota" and play an important role in health and disease. Recent research suggests that alterations in the skin microbiota may underlie chronic wound pathology. Probiotics are bacteria or yeast that confer a health benefit on the host and may have a role in preventing and treating nonhealing wounds by modulating host-microbe interactions. METHODS: The English literature on skin microbiota, chronic wounds, biofilms, and probiotics is reviewed. RESULTS: Recent evidence indicates that disruption of microbial communities and bacteria-host interactions may contribute to impaired wound healing. Preclinical and human studies highlight the potential of probiotics to prevent or treat various infectious, immune-mediated, and inflammatory diseases. CONCLUSIONS: Advances in molecular sequencing and microbiology have shed light on the importance of the human microbiota in development, health, and disease. Probiotics represent a novel approach to altering the microbial environment with beneficial bacteria. Ongoing challenges include the need for better understanding of therapeutic mechanisms, improved regulation of manufacturing practices, and validation in controlled human trials. Current evidence suggests that probiotic-based therapies have considerable potential to exploit host-microbe relationships and improve clinical outcomes.