[BCG: an almost 100-year-old vaccine]. / BCG: een bijna 100 jaar oud vaccin.

There has been a vaccine against tuberculosis (TB) since 1921. This vaccine contains Bacillus Calmette-Guérin (BCG), a live attenuated strain of the tubercle bacterium Mycobacterium bovis. The vaccine is fairly effective in children, but protection is poor in adults. Protection lasts about 15 years. The vaccine is safe for immunocompetent people, provided it is administered intracutaneously and at the correct dose. This article looks back at the development of the tuberculin skin test and BCG vaccine, and their use in the Netherlands.

The history of tuberculosis: from the first historical records to the isolation of Koch's bacillus.

Tuberculosis (TB) is a contagious, infectious disease, due to Mycobacterium tuberculosis (MT) that has always been a permanent challenge over the course of human history, because of its severe social implications. It has been hypothesized that the genus Mycobacterium originated more than 150 million years ago. In the Middle Ages, scrofula, a disease affecting cervical lymph nodes, was described as a new clinical form of TB. The illness was known in England and France as "king's evil", and it was widely believed that persons affected could heal after a royal touch. In 1720, for the first time, the infectious origin of TB was conjectured by the English physician Benjamin Marten, while the first successful remedy against TB was the introduction of the sanatorium cure. The famous scientist Robert Koch was able to isolate the tubercle bacillus and presented this extraordinary result to the society of Physiology in Berlin on 24 March 1882. In the decades following this discovery, the Pirquet and Mantoux tuberculin skin tests, Albert Calmette and Camille Guérin BCG vaccine, Selman Waksman streptomycin and other anti-tuberculous drugs were developed.

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 ongoing challenge of latent tuberculosis.

The global health community has set itself the task of eliminating tuberculosis (TB) as a public health problem by 2050. Although progress has been made in global TB control, the current decline in incidence of 2% yr(-1) is far from the rate needed to achieve this. If we are to succeed in this endeavour, new strategies to reduce the reservoir of latently infected persons (from which new cases arise) would be advantageous. However, ascertainment of the extent and risk posed by this group is poor. The current diagnostics tests (tuberculin skin test and interferon-gamma release assays) poorly predict who will develop active disease and the therapeutic options available are not optimal for the scale of the intervention that may be required. In this article, we outline a basis for our current understanding of latent TB and highlight areas where innovation leading to development of novel diagnostic tests, drug regimens and vaccines may assist progress. We argue that the pool of individuals at high risk of progression may be significantly smaller than the 2.33 billion thought to be immune sensitized by Mycobacterium tuberculosis and that identifying and targeting this group will be an important strategy in the road to elimination.

Purified protein derivatives of tuberculin--past, present, and future.

The tuberculin skin test, which involves monitoring the immune reaction to an injection of purified protein derivative (PPD), has been the most widely used method for detecting infection with Mycobacterium tuberculosis since its development in 1930s. Until recently, the molecular composition of PPD was unknown. This thwarted the discovery of improved skin testing reagents and drastically hindered efforts to define the mechanism of action. Proteomic evaluation of PPD combined with a detailed analysis in the guinea pig model of tuberculosis led to further definition of the molecular composition of PPD. This communication reviews the history and current status of PPD, in addition to describing candidate next-generation PPD reagents, based on the use of an individual protein or protein cocktails.

A brief history of tuberculosis in Iran during the 19th and 20th centuries.

The history of tuberculosis as a worldwide fatal illness traces back to antiquity, a well-known disease in ancient civilizations. However, its causative agent remained unidentified until the last decades of the 19th century, when discovered by Robert Koch. In due course, preparation of the BCG vaccine, application of the Mantoux intradermal diagnostic tuberculosis test and administration of proper antituberculosis medications eventually controlled tuberculosis. However, despite these significant advancements tuberculosis remained uneradicated, particularly in developing countries after the emergence of both multidrug-resistant tuberculosis and HIV co-infection. Presented here, is a brief review of the history of tuberculosis in the world as well as its historical background in Iran, mainly during the 19th and 20th centuries.

Testing for tuberculosis infection.

The diagnosis and management of latent tuberculosis infection (LTBI) has evolved over the last several years. New guidelines have been issued as our knowledge base continues to improve. We summarize the current understanding of this important topic and review the pathophysiology of the purified protein derivative test, its use and interpretation, the concept of targeted tuberculin testing, the management of latent tuberculosis infection (LTBI), and the role of the newer testing modalities.

The history of tuberculosis.

Tuberculosis has claimed its victims throughout much of known human history. It reached epidemic proportions in Europe and North America during the 18th and 19th centuries, earning the sobriquet, "Captain Among these Men of Death." Then it began to decline. Understanding of the pathogenesis of tuberculosis began with the work of Théophile Laennec at the beginning of the 19th century and was further advanced by the demonstration of the transmissibility of Mycobacterium tuberculosis infection by Jean-Antoine Villemin in 1865 and the identification of the tubercle bacillus as the etiologic agent by Robert Koch in 1882. Clemens von Pirquet developed the tuberculin skin test in 1907 and 3 years later used it to demonstrate latent tuberculous infection in asymptomatic children. In the late 19th and early 20th centuries sanatoria developed for the treatment of patients with tuberculosis. The rest provided there was supplemented with pulmonary collapse procedures designed to rest infected parts of lungs and to close cavities. Public Health measures to combat the spread of tuberculosis emerged following the discovery of its bacterial cause. BCG vaccination was widely employed following World War I. The modern era of tuberculosis treatment and control was heralded by the discovery of streptomycin in 1944 and isoniazid in 1952.

[Clemens Freiherr von Pirquet, developer of the concept of allergy]. / Revolutionär am Krankenbett.

The pediatrician and scientist, Clemens Freiherr von Pirquet (1874-1929) was the first to coin the term "allergy". His experiments with Behring's serum, which he administered to sick children, led him to an awareness of an interaction between the human organism and pathogens. In his article published in the Müncher Medizinischen Wochenschrift in 1906, he laid the foundation stone for modern allergology.