Anton Ghon and His Colleagues and Their Studies of the Primary Focus and Complex of Tuberculosis Infection and Their Relevance for the Twenty-First Century.

Anton Ghon is well known in the field of childhood tuberculosis, and the tuberculosis primary focus and complex are frequently called the Ghon focus and complex; this is largely the result of the wide publication of the English translation of his monograph "Der primäre Lungenherd bei der Tuberkulose der Kinder." Ghon's studies are frequently quoted, but precise details of his monograph are neglected, his results often misquoted, and his later publications virtually unknown. This review highlights aspects of Ghon's anatomical pathology studies in children and adults not necessarily dying of tuberculosis but with signs of tuberculosis infection. Ghon found a single primary tuberculosis focus in approximately 80% of tuberculosis-infected children situated close to the pleura in two-thirds of cases. Cavitation of the focus was common, and lymphatic spread involved lymph nodes in the abdomen and neck in many children. Studies amongst adults and children frequently found the healed primary tuberculosis focus to be completely calcified without histological signs of tuberculosis activity; however, particularly in the presence of pulmonary tuberculosis, histological signs of tuberculosis activity were often found in the lymph nodes of the angulus venosus, despite apparent healing with extensive calcification. Both earlier studies and more recent investigations, with molecular biological tools, unavailable to Ghon and earlier researchers, have confirmed the presence of viable mycobacteria in apparently normal or healed thoracic nodes and also found molecular biological indications of viable mycobacteria in these nodes. As suggested by Ghon, lympho-haematogenous spread of tuberculosis may be more common than is usually appreciated.

Tuberculosis chemotherapy centre - The beginning.

OBJECTIVE: Establishment of a TB research centre with the aim of studying the feasibility of domiciliary treatment for the masses. METHODS: In-depth case study of the TB chemotherapy Centres's initial activities and development. RESULTS: Successful setting up of a research centre in 1956 at Madras. CONCLUSION: Four agencies collaborated successfully to demonstrate that domiciliary treatment for the masses is feasible.

Paradigm shift in efforts to end TB by 2025.

TB is a deadly infectious disease, in existence since time immemorial. This article traces the journey of TB developments in the last few decades and the path breaking moments that have accelerated the efforts towards Ending TB from National Tuberculosis Control Program (NTCP 1962-1992) to Revised National Tuberculosis Control Program (RNTCP - 1992-2019) and to National Tuberculosis Elimination Program (NTEP) as per the vision of Honorable Prime Minister of India. From increased funding for TB, the discovery of newer drugs and diagnostics, increased access to health facilities, greater investment in research and expanded reach of public health education, seasoned with TB activism and media's proactive role, private sector participation to political advocacy and community engagement, coupled with vaccine trials has renewed the hope of finding the elusive and miraculous breakthrough to END TB and it seems the goal is within the realms of the possibility. The recent paradigm shift in the policy and the drive of several states & UTs to move towards TB free status through rigorous population-based vulnerability mapping and screening coupled with active case finding is expected to act as the driving force to lead the country towards Ending TB by 2025. Continued investments in research, innovations and availability of more effective drugs and the vaccines will add to existing armamentarium towards Ending TB.

Tuberculosis research conducted over the years at the ICMR-National Institute for Research in Tuberculosis (ICMR-NIRT).

This review article highlights some of the key research conducted at the ICMR-National Institute for Research in Tuberculosis (ICMR-NIRT) over the years since its inception in 1956 till the present. The research carried out in the field of tuberculosis at ICMR-NIRT has been a joint effort between the ICMR, NIRT, the TB control program in India with assistance from World Health Organization (WHO) and the National Institutes of Health (NIH), USA. The research carried out at ICMR-NIRT has helped to formulate the national guidelines for the control and the management of tuberculosis in India. The major highlights of the research carried out at ICMR-NIRT are provided in this manuscript.

A systemic review on tuberculosis.

Tuberculosis (TB), which is caused by bacteria of the Mycobacterium tuberculosis complex, is one of the oldest diseases known to affect humans and a major cause of death worldwide. Tuberculosis continues to be a huge peril disease against the human population and according to WHO, tuberculosis is a major killer of the human population after HIV/AIDS. Tuberculosis is highly prevalent among the low socioeconomic section of the population and marginalized sections of the community. In India, National strategic plan (2017-2025) has a national goal of elimination of tuberculosis by 2025. It requires increased awareness and understanding of Tuberculosis. In this review article history, taxonomy, epidemiology, histology, immunology, pathogenesis and clinical features of both pulmonary tuberculosis (PTB) and extra-pulmonary tuberculosis (EPTB) has been discussed. A great length of detailed information regarding diagnostic modalities has been explained along with diagnostic algorithm for PTB and EPTB. Treatment regimen for sensitive, drug resistant and extensive drug resistant tuberculosis has been summarized along with newer drugs recommended for multi drug resistant tuberculosis. This review article has been written after extensive literature study in view of better understanding and to increase awareness regarding tuberculosis, as a sincere effort that will help eliminate tuberculosis off the face of the earth in near future.

Tuberculosis in Iran: a historical overview from al-Tabari, Rhazes, Avicenna and Jorjani to Abolhassan Ziya-Zarifi. Old and new pioneers in the fight against tuberculosis: challenges, pitfalls and hopes.

Tuberculosis is a serious respiratory infectious disease, caused by Mycobacterium tuberculosis bacteria. It has always represented a permanent, serious public health challenge over the course of human history, because of its severe epidemiological, clinical and societal implications. The present review aims at over-viewing the contributions of the Iranian medicine to the control, management and treatment of tuberculosis, from the glorious past of the eighth-ninth centuries to the present, from Ali Abu al-Hasan Ahmad ibn Sahl-e Rabban al-Tabari to Rhazes, Avicenna, Jorjani and Abolhassan Ziya-Zarifi. However, despite the efforts, tuberculosis and, in particular, multidrug-resistant tuberculosis still represent a great public health concern in Iran. On the other hand, this country can capitalize on its millennial, incredibly rich story of major achievements in the battle against tuberculosis to develop and implement ad hoc public health programs for the control of the disorder, including targeted and specialized interventions.

Tuberculosis in Siena: evolution of the disease and its treatment, from the Unification of Italy to the 1930s.

Between the end of the nineteenth century and the first half of the twentieth century, the city of Siena experienced elevated tuberculosis-related morbidity and mortality, to the point that on January 1, 1929 the newspaper La Nazione wrote that "Siena ranks second in the official Tuberculosis (TB) incidence rate". The author presents statistical data relating to a time span ranging from 1898 to 1935, interpreting them in light of social and sanitary conditions found in the city. The result is an exhaustive picture of the most important actions implemented at city level to prevent tuberculosis and to assist and treat the sick, such as: the creation of seaside hospices conceived by Carlo Livi for children suffering from scrofula, as well as centers committed to the prevention of childhood poverty and malnutrition; the realization of activities in the green areas of the ramparts of the Fortress, upon recommendation by the great hygienist Achille Sclavo; the establishment of a Preventorium on the premises of the Monastery of Santa Maria Maddalena to accommodate children from families that included pulmonary tuberculosis patients, and countless activities carried out by the Anti-TB Dispensary. Of particular interest is the identification of the main cause of high TB incidence in the unhealthy houses located in some areas of Siena's district, which, in 1930 engendered a lively debate hinging upon the notion of building restoration.

The Struggle Against Infant Scrofula in Siena Between the Nineteenth and Twentieth Centuries.

Poverty, high population density and unhealthy dwellings in Siena's historic district accounted for the spread of tuberculosis in its various forms between the mid-nineteenth century and the first three decades of the twentieth century. In this paper, the author relies on statistical data relating to a time span between 1898 and 1935 to discuss the high incidence of scrofula, or tuberculosis of the lymphatic glands, among Siena's infant population.The result is a description of the most important actions implemented at city level to prevent tuberculosis and to assist and treat sick children: stays in seaside hospices promoted by Carlo Livi in order prevent and treat poor and malnourished children, the establishment of a Preventorium to accommodate children from families that included members infected with pulmonary tuberculosis, the realization of activities in the green areas of the Fortress on advice of Achille Sclavo. Furthermore, the author recalls the work of great hygienist Sclavo to raise awareness of the hygienic practices among Siena's population, which was fundamental in the prevention of epidemic diseases such as tuberculosis.

Between Donor Interest, Global Models and Local Conditions: Treatment and Decision-Making in the Somalia-Finland Tuberculosis Control Project, 1981-3.

Despite numerous global health initiatives after World War II, tuberculosis still poses a major threat in sub-Saharan Africa. This article examines one attempt to tackle this problem: the Somalia-Finland Tuberculosis Control Project. Conducted in the 1980s as a bilateral development aid project between the two countries, it became the most extensive - and expensive - tuberculosis initiative in Somalia in that decade. An interesting feature of the project is that, despite a lack of previous experience in tuberculosis work in developing countries, the Finnish partner decided not to follow the WHO global guidelines designed to standardise tuberculosis activities across the developing world. Instead, Finns established their own treatment programme based on X-ray and short-course chemotherapy - otherwise rarely used in clinical practice in Africa. Through a close reading and comparison of the correspondence, project plans, memos and minutes, the article analyses the formation of this strategy. Focusing on ground-level decision-making, it argues that the decisions were based not only on a belief in the superior clinical effectiveness of these methods, but also on the fact that they better suited Finnish ambitions and project logic. Thus, the article supports the notion that donor perspectives on resources and project objectives determined what was seen as feasible treatment in a developing country. By shedding light on the debate between the supporters of short-course chemotherapy and the WHO standard treatment strategy, it also contributes to the early history of DOTS (directly observed treatment, short course).

Organ-specific dose coefficients derived from Monte Carlo simulations for historical (1930s to 1960s) fluoroscopic and radiographic examinations of tuberculosis patients.

This work provides dose coefficients necessary to reconstruct doses used in epidemiological studies of tuberculosis patients treated from the 1930s through the 1960s, who were exposed to diagnostic imaging while undergoing treatment. We made use of averaged imaging parameters from measurement data, physician interviews, and available literature of the Canadian Fluoroscopy Cohort Study and, on occasion, from a similar study of tuberculosis patients from Massachusetts, United States, treated between 1925 and 1954. We used computational phantoms of the human anatomy and Monte Carlo radiation transport methods to compute dose coefficients that relate dose in air, at a point 20 cm away from the source, to absorbed dose in 58 organs. We selected five male and five female phantoms, based on the mean height and weight of Canadian tuberculosis patients in that era, for the 1-, 5-, 10-, 15-year old and adult ages. Using high-performance computers at the National Institutes of Health, we simulated 2,400 unique fluoroscopic and radiographic exposures by varying x-ray beam quality, field size, field shuttering, imaged anatomy, phantom orientation, and computational phantom. Compared with previous dose coefficients reported for this population, our dosimetry system uses improved anatomical phantoms constructed from computed tomography imaging datasets. The new set of dose coefficients includes tissues that were not previously assessed, in particular, for tissues outside the x-ray field or for pediatric patients. In addition, we provide dose coefficients for radiography and for fluoroscopic procedures not previously assessed in the dosimetry of this cohort (i.e. pneumoperitoneum and chest aspirations). These new dose coefficients would allow a comprehensive assessment of exposures in the cohort. In addition to providing newly derived dose coefficients, we believe the automation and methods developed to complete these dosimetry calculations are generalizable and can be applied to other epidemiological studies interested in an exposure assessment from medical x-ray imaging. These epidemiological studies provide important data for assessing health risks of radiation exposure to help inform the current system of radiological protection and efforts to optimize the use of radiation in medical studies.

Prescribing Patterns for Treatment of Mycobacterium avium Complex and M. xenopi Pulmonary Disease in Ontario, Canada, 2001-2013.

Surveys suggest that clinicians diverge from guidelines when treating Mycobacterium avium complex (MAC) pulmonary disease (PD). To determine prescribing patterns, we conducted a cohort study of adults >66 years of age in Ontario, Canada, with MAC or Mycobacterium xenopi PD during 2001-2013. Using linked laboratory and health administrative databases, we studied the first treatment episode (>60 continuous days of >1 of a macrolide, ethambutol, rifamycin, fluoroquinolone, linezolid, inhaled amikacin, or, for M. xenopi, isoniazid). Treatment was prescribed for 24% MAC and 15% of M. xenopi PD patients. Most commonly prescribed was the recommended combination of macrolide, ethambutol, and rifamycin, for 47% of MAC and 36% of M. xenopi PD patients. Among MAC PD patients, 20% received macrolide monotherapy and 33% received regimens associated with emergent macrolide resistance. Although the most commonly prescribed regimen was guidelines-recommended, many regimens prescribed for MAC PD were associated with emergent macrolide resistance.

Detection, survival and infectious potential of Mycobacterium tuberculosis in the environment: a review of the evidence and epidemiological implications.

Much remains unknown about Mycobacterium tuberculosis transmission. Seminal experimental studies from the 1950s demonstrated that airborne expulsion of droplet nuclei from an infectious tuberculosis (TB) patient is the primary route of transmission. However, these findings did not rule out other routes of M. tuberculosis transmission. We reviewed historical scientific evidence from the late 19th/early 20th century and contemporary studies investigating the presence, persistence and infectiousness of environmental M. tuberculosis We found both experimental and epidemiological evidence supporting the presence and viability of M. tuberculosis in multiple natural and built environments for months to years, presumably following contamination by a human source. Furthermore, several studies confirm M. tuberculosis viability and virulence in the environment using guinea pig and mouse models. Most of this evidence was historical; however, several recent studies have reported consistent findings of M. tuberculosis detection and viability in the environment using modern methods. Whether M. tuberculosis in environments represents an infectious threat to humans requires further investigation; this may represent an untapped source of data with which to further understand M. tuberculosis transmission. We discuss potential opportunities for harnessing these data to generate new insights into TB transmission in congregate settings.

History of Pulmonary Tuberculosis.

Tuberculosis (TB) parallels the history of human development from the Stone Age to the present. TB continues to be in the top 10 causes of global human mortality over that period. This article highlights the history of pulmonary TB from the onset of human existence to the present. Despite its long history, TB was slowly identified as a major cause of disease, and defined causation and significant treatment strategies advances over the past 150 years. TB remains a major challenge for definitive global prevention and cure. This article gives a brief overview of the history of TB.

O meu samba está de luto: a tuberculose na imprensa carioca e nas letras das composições de Noel Rosa (1930-1938)

A pesquisa tem por objetivos identificar se (e como) a tuberculose influenciou no processo criativo do compositor popular Noel Rosa, morto aos 26 anos em decorrência da doença; e analisar a repercussão na imprensa escrita carioca das mortes dos sambistas Noel Rosa, José Barbosa da Silva (Sinhô) e Luís Barbosa, todos tuberculosos e falecidos precocemente. A obra musical de Noel Rosa é robusta com cerca de 300 composições. A pesquisa se desenvolveu a partir da seleção de 28 músicas que abordam temas variados como regeneração, sofrimento, culpa, boemia, cuidado e doença. A ideia central é identificar elementos que aproximem o universo criativo do compositor com a sua trajetória de artista sadio/doente, bem como indicar a apropriação por parte de Noel Rosa do discurso higienista, em voga na década de 1930. Além das músicas, três cartas escritas para seu médico, sua sogra e sua mãe são analisadas nesta pesquisa. Em relação aos jornais, estabeleceu-se um estudo comparativo da repercussão das mortes dos três sambistas a partir da seleção de 60 notícias, artigos, notas obituárias e reportagens veiculadas em 14 jornais que circularam na cidade do Rio de Janeiro, na década de 1930. O objetivo é identificar as semelhanças e diferenças na abordagem das mortes dos artistas, destacando especialmente a presença de um discurso de culpabilidade da vítima pelo acometimento da doença.(AU)