Von Pirquet Research Articles

Remembering innovative paediatrician Clemens von Pirquet on the 150th anniversary of his birth.

Remembering innovative paediatrician Clemens von Pirquet on the 150th anniversary of his birth.

Clemens von Pirquet: Preeminent researcher, teacher, clinician and advocate.

Clemens von Pirquet: Preeminent researcher, teacher, clinician and advocate.

Doubtful Guests, Harassed Hosts, and the Golden Rule

Doubtful Guests, Harassed Hosts, and the Golden Rule

Early priming of asthma and respiratory allergies: Future aspects of prevention: A statement by the European Forum for Education and Research in Allergy and Airway Disease (EUFOREA) and the EAACI-Clemens von Pirquet Foundation.

In order to summarize recent research on the prevention of allergies-particularly asthma-and stimulate new activities for future initiatives, a virtual workshop sponsored by the EAACI Clemens von Pirquet foundation and EUFOREA was held in October 2021. The determinants of the "allergic march" as well as the key messages from intervention studies were reviewed by an international faculty of experts. Several unmet needs were identified, and a number of priorities for future studies were proposed.

Latent tuberculosis testing through the ages: the search for a sleeping killer.

Tuberculosis has been present in the world’s population for as long as there has been written language. It is a disease known to the ancient Egyptians, Greeks, Romans, and Hebrews, but its etiology eluded the world for thousands of years. Even after the germ theory was accepted and early scientists hypothesized a pathogen as the cause, the identity of the sleeping killer in society remained a mystery. That is until Robert Koch was able to grow and visualize Mycobacterium tuberculosis. Koch introduced his Old Tuberculin solution as a diagnostic therapy of tuberculosis (TB), with the intent to reduce the number of infected persons and stop its spread. Old Tuberculin’s ability to treat TB proved minimal, but its diagnostic potential paved the way for more effective tests from von Pirquet, Calmette, Wolff-Eisner, and Mantoux. Florence Seibert set out to identify and purify the active principle in Koch’s Old Tuberculin and ended up creating purified protein derivative (PPD) tuberculin which is still used as the standard for the tuberculin skin test (TST). Interferon-γ release assays (IGRAs) are a more modern diagnostic tool for detecting latent TB infection that offer some benefits (and some disadvantages) to TST. TSTs and IGRAs can determine if an individual has been infected with M. tuberculosis but are equally unable to predict progression to active tuberculosis, the diagnosis of which relies on assessment of clinical symptoms, radiographic imaging, and sample culture.

Allergic inflammation

Relatively not so long ago, the doctrine of the inflammatory response was enriched by the concept of "allergic inflammation" (von Pirquet 1907-08). However, the subsequent experimental and clinical study of these inflammatory forms has deepened our understanding of the pathogenesis of each inflammatory reaction so much that it can rightfully be called a stage in the new history of inflammation. From time immemorial, the doctor knew the variety of forms of development and course of inflammation. The construction of these numerous modifications of inflammation in most cases remained unclear. In his practice, each doctor encounters forms of extremely rapidly developing inflammation. Notae verae inflammationis is especially prominent in these cases. Tissue lesions end in necrosis. This one symptom already indicates the rapid development of this form of inflammation. But the rate of its formation can also be registered when studying other inflammatory signs preceding necrosis. A characteristic feature of the development of a normal skin test in an allergic person is the appearance within the first half an hour, literally "before the eyes" of the observer, hyperemia, edema on the periphery of the injection and even infiltration at the injection site.

Clemens von Pirquet

Clemens Peter Freiherr von Pirquet, a great physician-scientist who described serum sickness and opened the field of allergy, was born in Hirschstetten near Vienna on 12 May 1874 into a...

Editorial introductions.

Editorial introductions.

Single Dose Oral Food Challenge at Diagnosis Accelerates Cows Milk Allergic Infants’ Acquisition of Oral Tolerance to Milk, But Progress is Influenced by Maternal Anxiety

Background: Cow’s milk protein allergy (CMPA) is one of the most common food allergies in infancy. Parents often display significant anxiety about this condition. Single dose challenges are a new method of assessing dose reactivity in food allergic children. Methods: We recruited children referred for evaluation of CMPA to a randomised, controlled trial of single dose challenge to cow’s milk, using the validated dose of milk that would elicit reactions in 5% of CMPA subjects - the ED 05 - before implementation of graded exposure to CM (using the 12 step iMAP Milk Tolerance Induction Ladder) at home. Parents completed food allergy quality of life and State and Trait Anxiety Inventories (STAI). Results: Sixty patients were recruited, 57 (95%) were followed to 6 months. By 6 months 27/37 (73%) intervention subjects had reached step 6 or above on the milk ladder compared to 10/20 (50%) control subjects (p=0.048). By 6 months 11/37 (30%) intervention subjects had reached step 12 (ie drinking unheated cow’s milk) compared to 2/20 (10%) of the controls (p=0.049). Twelve months post randomisation 31/36(86%) of the intervention group and 15/19(79%) of the control group were on step 6 or above. However, 24/37 (65%) of the intervention group were at step 12 compared to 7/20 (35%) of the control group (p=0.03). Maternal STAIs were significantly associated with their infants’ response/progress on the milk ladder and with changes in skin prick test and spIgE levels at 6 and 12 months. Conclusion: Using the 12 step iMAP milk ladder accelerates natural tolerance induction in infants under 12 months with CMPA. A supervised single dose at the ED 05 significantly accelerates this further, probably by giving parents the confidence to proceed. Maternal anxiety generally reflects infants’ progress towards tolerance but preexisting high levels of maternal anxiety are associated with poorer progress. Funding: YD was in receipt of a Clinical Research Fellowship from the National Childrens Research Centre Ireland. Declaration of Interest: AM received research funding from Aimmune Therapeutics, RvR declares consultancies for HAL Allergy BV, Citeq BV, Angany Inc, speaker fees from HAL Allergy BV, ThermoFisher Scientific, ALK and stock options from Angany Inc. ADG receives research funding and speaker fees from Aimmune Therapeutics JO’BH receives research funding, speaker fees and consultancy fees from Aimmune Thereputics, research funding and speaker fees from DBV Technologies, research funding from Johnson&Johnson, Clemens von Pirquet Foundation and Temple st Hospital Research Foundation. Ethical Approval: Ethical approval was obtained from the Clinical Research Ethics Committees of the Cork Teaching Hospitals and Crumlin Hospital. Approval was granted on 26th September 2017.

Editorial introductions

Editorial introductions

Editorial introductions

Editorial introductions

Current state and future of pediatric allergology in Europe: A road map.

The history of pediatric allergology (PA) in Europe is relatively youthful, dating back to 1984, when a small group of pediatricians founded the European Working Group on Pediatric Allergy and Immunology-later giving rise to ESPACI (European Society on Pediatric Allergology and Clinical Immunology). In 1990, the first dedicated journal, Pediatric Allergy and Immunology (PAI), was founded. There are striking differences across Europe, and even within European countries, in relation to the training pathways for doctors seeing children with allergic disease(s). In 2016, the EAACIClemens von Pirquet Foundation (CvP) organized and sponsored a workshop with the European Academy of Allergy and Clinical Immunology (EAACI) Pediatric Section. This collaboration focussed on the future of PA and specifically on education, research, and networking/ advocacy. The delegates representing many countries across Europe have endorsed the concept that optimal care of children with allergic diseases is delivered by pediatricians who have received dedicated training in allergy, or allergists who have received dedicated training in pediatrics. In order to meet the needs of children and families with allergic disease(s), the pediatric allergist is highly encouraged to develop several networks. Our challenge is to reinforce a clear strategic approach to scientific excellence to across our member base and to ensure and enhance the relevance of European pediatric research in allergy. With research opportunities in basic, translational, clinical, and epidemiologic trials, more trainees and trained specialists are needed and it is an exciting time to be a pediatric allergologist.

Clemens von Pirquet: A Remarkable Life and Career

From 1908 to 1929, Clemens von Pirquet was one of the world's most acclaimed pediatricians. Von Pirquet (1874-1929) trained at Vienna's Universitäts Kinderklinic under Theodor Escherich, the first Pediatric Infectious Diseases physician [1], and became the first Professor and Chair of Pediatrics at Johns Hopkins in 1909. He then succeeded his mentor Escherich as Professor and Chair of Pediatrics in Vienna, the most prestigious European pediatric position, when Escherich died unexpectedly in 1911. He held that position in Vienna until his shocking double suicide at age 54 with his wife in 1929. Von Pirquet's pioneering contributions from 1903 to 1910 related to host reactions to foreign substances, providing much of the foundation for modern "Immunology". In 1905, he and his student Bela Schick described and named "serum sickness" in children administered animal antiserum. He recognized that animal antiserum resulted in both protection against an infection but also sensitization (sometimes with serious or fatal consequences), ie, that immune responses caused some diseases. In 1906, he proposed the term "allergy" for the altered reactivity induced by what he termed an "allergen", a foreign substance. He recognized that sensitization to an allergen leads to accelerated responses on subsequent allergen administration, analogous to differences between primary and subsequent smallpox vaccine responses. In 1908, von Pirquet presented his invention, the "tuberculin skin test", recognizing its ability to identify individuals with previous tuberculosis infection, then the most prevalent infectious disease. This led to the new understanding that many or most tuberculosis-infected individuals are asymptomatic but at risk for future active disease, introducing the concept of "latent tuberculosis". Von Pirquet was a consummate pediatrician-scientist, translating scientific discoveries directly into improved care of children, and he also pioneered study of the social, nutritional, and public health aspects of pediatrics, especially during and after World War I.

The discovery of IgE 50 years later

In 1906, Von Pirquet1 used the term supersensitivity without immunity to describe (1) symptoms of inhalant allergy, (2) positive immediate skin test results, and (3) the fact that the results of other tests of immunity were not positive in these patients. The other tests he referred to were precipitin tests and complement fixation. Thus, he opened up the question of serum tests for supersensitivity. In 1919, Ramirez2 reported that a patient who had received a blood transfusion from a horse allergic donor became allergic to horse dander. At this point, Prausnitz and Kustner3 set out to investigate whether the serum of allergic individuals contained a factor or factors that could sensitize the skin. In 1921, they reported that the local injection of serum from a fish allergic individual, Kustner, to an individual who was only allergic to pollen, Prausnitz, would transfer specific sensitivity.3 This transfer of sensitivity came to be known as the P-K test and was used widely to study sensitivity not only to common allergens but also to extracts as diverse as those obtained from schistosomes.4,5 Furthermore, in New York, Cooke et al6 identified that there were other antibodies in the serum that increased during desensitization treatment and could block the skin-sensitizing activity. By the 1950s, it was clear that the transferred sensitivity was specific, that it could be diluted extensively, and that the skin remained locally sensitive for days if not weeks after the injection of serum.7,8 It was also already clear that the ability to sensitize the skin was lost after moderate heating of the serum.7 Several studies had also been reported on the physical properties of P-K activity. Indeed, Heimlich et al9 at Cal Tech reported on the sedimentation properties of skin-sensitizing antibodies in 1960. However, the studies before 1964 had not succeeded in defining the nature of these antibodies.

The sticky relationship between allergies and infections.

For this general concept of a changed reactivity, I proposed the term allergy Clemens von Pirquet, 1906 [1].

Terminology of allergic phenomena.

Over the last 2,000 years a variety of terms have been used for the description of phenomena possibly related to allergy. Many have been forgotten, while some of them have remained. In Greco-Roman literature the term 'idiosyncrasy' was used to describe an individual characterization of a health condition, possibly comparable to 'constitution'. The same term was also used to describe individual reaction patterns, and the term 'antipathy' was used in a similar sense. 'Hypersensitivity' originated from the German word 'Überempfindlichkeit' and was first used in a medical sense by Emil von Behring when he described untoward reactions to his antitoxin containing serum therapy. 'Anaphylaxis' was coined by Richet and Portier to describe the new phenomenon of a life-threatening general pathogenic reaction after repeated injection of antigen. In 1906, Clemens von Pirquet introduced the term 'allergy' in order to bring more clarity to the confusing debate regarding protective and harmful immunity. In order to characterize the familial occurrence of hypersensitivity reactions such as asthma, hay fever and others, the American allergists A.F. Coca and R.A. Cooke introduced the term 'atopy'. Contrary to anaphylaxis, which was experimentally induced, this type of 'hypersensitiveness' occurred spontaneously. The nature of the pathogenic factor was called the 'atopic reagin' and was found to be transferable with serum by Prausnitz and Küstner. After the detection of immunoglobulin (Ig) E as the carrier of this type of hypersensitivity, the term 'atopy' gained a new sense, since IgE is a characteristic - yet not exclusive - parameter of the so-called atopic diseases. Clinically similar diseases such as asthma, rhinoconjunctivitis or eczema can be found in the absence of IgE, and are then called 'intrinsic' variants of the same disease.

Imagining ‘reactivity’: allergy within the history of immunology

An allergy is commonly understood to be an overreaction of the immune system to harmless substances that are misrecognised as foreign. This concept of allergy as an abnormal, misdirected immune response—a biological fault—stems from the idea that the immune system is an inherently defensive operation designed to protect the individual through an innate capacity to discriminate between the benign and toxic, or self and nonself. However, this definition of allergy represents a radical departure from its original formulation. Literally meaning ‘altered reactivity’, the term was coined in 1906 by Austrian paediatrician Clemens von Pirquet, to describe the fundamentally mutable nature of the immune response.This paper argues that the conventional interpretation of allergy-as-pathology derives from specific concepts of ‘organism’, ‘response’, and ‘normal’ immune function that have—for over a century—governed the perception and study of immune phenomena within immunology. Through an examination of Louis Pasteur’s conceptualisation of the host body/microorganism relationship, I argue that immunology is founded on a view of the organism as a discrete, autonomous entity, and on a concomitant notion of the immune response as essentially reactive. Revisiting the concept of ‘altered reactivity’, this paper points to the fact that allergy was initially posited as a general theory of immune responsiveness and, importantly, one that poses a significant challenge to orthodox notions of immunopathology. It suggests that Pirquet’s unique view of immune responsiveness presents an account of organismic or biological identity that encapsulates, rather than reduces, its ecological complexity.

Continuity and Innovation in Pediatric Allergy & Immunology

Continuity and Innovation in Pediatric Allergy & Immunology

Management of tuberculosis in HIV infection: where T-cells matter

Even 127 years after Robert Koch's identification of Mycobacterium tuberculosis as the causative agent of tuberculosis (TB), the diagnosis of active disease still depends in many parts of the world on the same tools that Koch has used: specifically staining of the bacilli and visual observation by microscopy 1. Thirty years later, von Pirquet developed the tuberculin skin-test (TST), which, instead of observing the pathogenic microbe itself, measures the immunological response to it 2. We now know that the specific induration in the skin-test is mediated by specifically activated T-lymphocytes that elicit a delayed-type hypersensitivity (DTH) response via production of a variety of inflammatory cytokines. While both test systems are still widely used, their sensitivity is highly variable and ranges from 20 to 60% for microscopy 3, 4, and 67 to 80% for skin-testing 5, 6. In patients with HIV infection and other forms of immunosuppression, the sensitivity is even worse and far beyond being adequate for a modern diagnostic test 7, 8. In their recent manuscript, Leidl et al. 9 now compare the performance …

A modern epidemic

Allergy: The History of a Modern Malady by Mark Jackson Reaktion Books, London, UK 288 pp, $40/£25 ISBN 1861892713 ![][1] The great epidemics of the past resulted from infection: influenza, yellow fever and the plague. Today, these have largely been replaced by new epidemics of chronic disease—such as cardiovascular disease and type II diabetes—the etiologies of which are as much social and economic as they are biological. In Allergy: The History of a Modern Malady , Mark Jackson traces one such epidemic from its roots in nineteenth‐century immunology to its current status as one of the most pervasive maladies afflicting mankind. In doing so, he has written a remarkably concise, accessible, and yet intellectual account of the essential role that history has in understanding the socioeconomic, cultural, and environmental origins of allergy and other modern diseases. Throughout the book, Jackson provides an historical overview of the term ‘allergy’, describing how its meaning has changed over time and how, at any one moment, its perception has varied between scientists, clinicians and the lay public. In 1905, Clemens von Pirquet, an Austrian … [1]: /embed/graphic-1.gif