Probable cases of tuberculosis in Early Medieval pastoralists of Eastern Europe.

Two anthropological collections of the 8-9th century AD from the forest-steppe area of the southern Eastern Europe has been the subject of analysis of the osteo-articular alterations concerning tuberculosis related lesions. According to archaeological data, the Mayaki and Dmitrievka groups are from the territory of Khazar Khaganate, which is well-known by historical data. It was a traditional population with settled pastoral farming. There were studied 292 adult human remains by macroscopic morphological and radiological methods. The completeness of the skeletons could have been better due to the intentional selection of their parts for the museum funds, so there were limitations for the differential diagnosis of TB by morphological criteria. In general, 31 individuals (20 men, 11 women) were marked as possible candidates with skeletal TB. The number of skeletons with possible specific infections from the two series is comparable, but according to sex distribution, there are some significant differences. If in the Dmitrievka group, there was approximately the same distribution of the number of cases of possible infected men and women; in the Mayaki group then there was a significant difference in the prevalence of the male sample. Various reasons can explain the observed differences. Firstly, we cannot rule out an error in the diagnosis of tuberculosis only by morphological methods since the preservation of the skeletons leaves much to be desired. Secondly, as it is known, only a few percent of tuberculosis patients show skeletal alterations, so the direct quantitative comparison cannot be adequate in paleopathological studies. The ambiguity of morphological criteria, particularly for destructive lesions of bone other than vertebrae, does not allow asserting that all identified cases result from TB. However, the results of differential diagnosis can underline that at least half of the skeletons have skeletal alterations most likely related to TB. The final analysis of the remains by aDNA methods will permit more certain confirmation of the diagnosis.

Tuberculosis before and after the Black Death (1346-1353 CE) in the Hospital of St John the Evangelist in Cambridge, England.

This research explores how the prevalence of tuberculosis (TB) in a medieval hospital was affected by the demographic and social changes that following the Black Death (1346-1353 CE), the initial years of the Second Plague Pandemic. To do this, skeletal remains of individuals buried at the Hospital of St John the Evangelist in Cambridge, England, that could be dated to living before (n = 77) or after (n = 55) the Black Death were assessed for evidence of TB (indicated by destructive lesions of the spine, ribs, large joints, and other recognised criteria). Overall, the odds of females having skeletal lesions caused by TB were over four times higher than males. No significant difference was detected in the prevalence rates in those who lived before and after the Black Death (7.8%, 6/77 before and 11.0%, 6/55 after). However, the odds of females having skeletal evidence of TB were over five times greater after the Black Death than they were before. These findings indicate that women may have been 1) more susceptible to TB, 2) surviving longer post-infection than men, and/or 3) that women with TB were more likely to be admitted to the Hospital especially following the Black Death. It is also possible that impairment due to TB infection may have been a contributing factor for entry into the Hospital for women but not men.

Tuberculosis: the sanatorium season in the early 20th century.

The creation of hospitals providing specialist care is not a prerogative of our time. As the world wonders how to cope with new pandemics and the age-old problems of the transmission of infections and the isolation of the sick, while the COVID-19 pandemic has been raging, it might be worth glancing back at the period - just over a century ago - when sanatoriums were set up in Italy as part of the fight against consumption.

Metagenomic analysis reveals mixed Mycobacterium tuberculosis infection in a 18th century Hungarian midwife.

The Vác Mummy Collection comprises 265 well documented mummified individuals from the late 16th to the early 18th century that were discovered in 1994 inside a crypt in Vác, Hungary. This collection offers a unique opportunity to study the relationship between humans and pathogens in the pre-antibiotic era, as previous studies have shown a high proportion of tuberculosis (TB) infections among the individuals. In this study, we recovered ancient DNA with shotgun sequencing from a rib bone sample of a 18th century midwife. This individual is part of the collection and shows clear skeletal changes that are associated with tuberculosis and syphilis. To provide molecular proof, we applied a metagenomic approach to screen for ancient pathogen DNA. While we were unsuccessful to recover any ancient Treponema pallidum DNA, we retrieved high coverage ancient TB DNA and identified a mixed infection with two distinct TB strains by detailed single-nucleotide polymorphism and phylogenetic analysis. Thereby, we have obtained comprehensive results demonstrating the long-time prevalence of mixed infections with the sublineages L4.1.2.1/Haarlem and L4.10/PGG3 within the local community in preindustrial Hungary and put them in context of sociohistorical factors.

Treatment or Prevention? the matter of Priority in the Anti-tuberculosis Movement at the Turn of the 20th Century France.

The purpose of this paper is to analyze discussions on the matter of priority in treatment and prevention that took place in the medical community, the government and social hygiene associations to tuberculosis referred to as one of the national calamity in France at the turn of the 20th century. In other words, it is to show that treatment and prevention have complementary properties in France's anti-tuberculosis movement, considering the discussions on which institutions should preferably be expanded - between the Sanatorium that values medical treatment and the anti-tuberculosis dispensary that values social prevention. Tuberculosis, which is known to have existed from the ancient times, spread to the era of industrialization and urbanization, resulting in a large loss of lives in the second half of the 19th century following cholera in the first half of the century. Starting in Germany in the middle of this century, Sanatorium established a treatment for tuberculosis patients with air therapy, proper exercise or rest, and diet. In France, a public Sanatorium was built for the lower class, not like a luxury resort style Sanatorium for the wealthy class, from the 1890s. The spread was slow, however, due to financial problems. In the 1900s, anti-tuberculosis dispensary as a health center were increasingly built in working class quarters. The debate over whether to support the sanatorium or the dispensary was ignited at first, but since the mid-to-late 1900s, the two institutions' roles, namely, medical treatment and social prevention, have been recognized as complementary. The Anti-tuberculosis dispensary Act of 1916 and the Sanatorium Act of 1919 systematically supported the complementary relationship between treatment and prevention in fighting against tuberculosis.

Against settler colonial iatrogenesis: Inuit resistance to treatment in Indian Hospitals in Canada.

Canada's program to examine, transfer and treat Indigenous and Inuit peoples with tuberculosis in Indian Hospitals (ca. 1936 and 1969) has generally been framed by official narratives of population health, benevolence, and care. However, letters written by Inuit patients in Indian hospitals and their kin, and which were addressed to government officials and translated by government employees, challenge this assumption. By focusing on the harmful effects of the segregation and long-term detainment of Inuit peoples away from their communities, the letters theorize TB treatment as multiply harmful and iatrogenic. The letters also showcase how Inuit peoples resisted Indian Hospital treatment and articulated the need for care and treatment to occur within a network of intimate relations, rather than in distant sanatoriums.

BCG turns 100: its nontraditional uses against viruses, cancer, and immunologic diseases.

First administered to a human subject as a tuberculosis (TB) vaccine on July 18, 1921, Bacillus Calmette-Guérin (BCG) has a long history of use for the prevention of TB and later the immunotherapy of bladder cancer. For TB prevention, BCG is given to infants born globally across over 180 countries and has been in use since the late 1920s. With about 352 million BCG doses procured annually and tens of billions of doses having been administered over the past century, it is estimated to be the most widely used vaccine in human history. While its roles for TB prevention and bladder cancer immunotherapy are widely appreciated, over the past century, BCG has been also studied for nontraditional purposes, which include (a) prevention of viral infections and nontuberculous mycobacterial infections, (b) cancer immunotherapy aside from bladder cancer, and (c) immunologic diseases, including multiple sclerosis, type 1 diabetes, and atopic diseases. The basis for these heterologous effects lies in the ability of BCG to alter immunologic set points via heterologous T cell immunity, as well as epigenetic and metabolomic changes in innate immune cells, a process called "trained immunity." In this Review, we provide an overview of what is known regarding the trained immunity mechanism of heterologous protection, and we describe the current knowledge base for these nontraditional uses of BCG.

El mundo tuberculoso de Maxence Van der Meersch / The tuberculous world of Maxence Van der Meersch

Resumen Maxence Van der Meersch (1907-1951) fue un escritor francés cuyas novelas exponían las desigualdades sociales de la época. Entre ellas se destacan las asociadas con la tuberculosis, enfermedad frecuente, que aquejó a miembros de su familia y causó la muerte del autor. Las narraciones refieren las formas de presentación del mal, los métodos de diagnóstico, las actitudes de los pacientes y de su entorno, cómo afectaba a su situación laboral, los medios de subsistencia familiar y los recursos y complicaciones de los tratamientos. Al desarrollarse el argumento durante la llamada "era sanatorial de la tuberculosis" se retrata el acaecer en un sanatorio público. Se destaca la similitud de sucesos de la vida real del escritor y su esposa con los que se describen en parejas imaginadas en las novelas. El éxito de Van der Meersch fue opacado en sus últimos años por el agravamiento de su enfermedad y por críticas formuladas a algunos escritos. Resaltan las del cuerpo médico de esos años, que objetaron la crudeza del lenguaje, la inexactitud en la descripción de técnicas y, principalmente, por promover un objetado régimen antituberculoso.

Abstract Maxence Van der Meersch (1907-1951) was a French writer whose novels encompassed social inequities of the time. Among them, those related to tuberculosis are of special interest. This was a common disease that affected his family members and ultimately caused his death. In his narrations, the author refers to the various signs of the illness, the diagnostic methods, the patients' behaviour, their environment, how it affected their employment situation, the economic difficulties, treatment resources and complications. As the novels' plots are developed throughout the so called "sanatorial age of tuberculosis", the author describes the events occurring in a public sanatorium. The similitude among the situations lived by the writer and his wife, and those of the imaginary couples in the novels are highlighted. During his last years, Van der Meersch's success declined due to the complications of his illness, and because of the harsh criticism towards some of his writings. Particularly, the critiques posed by the medical professionals of the time, who rejected the raw language, inaccurate technical descriptions, and, above all, the promotion of an objected anti-tuberculosis regime.

A case of childhood tuberculosis from late mediaeval Somerset, England.

BACKGROUND: The remains of a 3-5 year-old child from the late mediaeval cemetery serving the Priory of St. Peter and St. Paul, Taunton, Somerset, UK was the subject of an aDNA study. OBJECTIVE: The aim was to distinguish between two differential diagnoses suggested by earlier osteological examination of the remains; either tuberculosis or Langerhans cell histiocytosis. FINDINGS: The remains tested positive for MTB complex markers, corroborating this diagnosis reached on osteological grounds. Based on positivity for the mtp40 element and a deletion in the pks15/1 locus, we conclude that infection was due to a strain of the human pathogen M.tuberculosis belonging to lineage 4. Although DNA recovered from the case was heavily fragmented, sex determination by amelogenin PCR suggested these are the remains of a young male child. The findings are discussed considering additions to the literature since the original report. CONCLUSIONS: Descriptions of tuberculosis in children from this period are rare and burial Sk2077 represents the first UK example of a pre-adolescent individual to have a molecular diagnosis combined with osteological pathology. This provides an important reference of childhood tuberculosis and insight into the likely presence of tuberculosis in the mediaeval adult population served by this cemetery.

The 1918 influenza pandemic did not accelerate tuberculosis mortality decline in early-20th century Newfoundland: Investigating historical and social explanations.

OBJECTIVES: The selective mortality hypothesis of tuberculosis after the 1918 influenza pandemic, laid out by Noymer and colleagues, suggests that acute exposure or pre-existing infection with tuberculosis (TB) increased the probability of pneumonia and influenza (P&I) mortality during the 1918 influenza pandemic, leading to a hastened decline of TB mortality in post-pandemic years. This study describes cultural determinants of the post-pandemic TB mortality patterns in Newfoundland and evaluates whether there is support for this observation. MATERIALS AND METHODS: Death records and historical documents from the Provincial Archives of Newfoundland and Labrador were used to calculate age-standardized island-wide and sex-based TB mortality, as well as region-level TB mortality, for 1900-1939. The Joinpoint Regression Program (version 4.8.0.1) was used to estimate statistically significant changes in mortality rates. RESULTS: Island-wide, females had consistently higher TB mortality for the duration of the study period and a significant shift to lower TB mortality beginning in 1928. There was no similar predicted significant decline for males. On the regional level, no models predicted a significant decline after the 1918 influenza pandemic, except for the West, where significant decline was predicted in the late-1930s. DISCUSSION: Although there was no significant decline in TB mortality observed immediately post-pandemic, as has been shown for other Western nations, the female post-pandemic pattern suggests a decline much later. The general lack of significant decrease in TB mortality rate is likely due to Newfoundland's poor nutrition and lack of centralized healthcare rather than a biological interaction between P&I and TB.

Human ancient DNA analyses reveal the high burden of tuberculosis in Europeans over the last 2,000 years.

Tuberculosis (TB), usually caused by Mycobacterium tuberculosis bacteria, is the first cause of death from an infectious disease at the worldwide scale, yet the mode and tempo of TB pressure on humans remain unknown. The recent discovery that homozygotes for the P1104A polymorphism of TYK2 are at higher risk to develop clinical forms of TB provided the first evidence of a common, monogenic predisposition to TB, offering a unique opportunity to inform on human co-evolution with a deadly pathogen. Here, we investigate the history of human exposure to TB by determining the evolutionary trajectory of the TYK2 P1104A variant in Europe, where TB is considered to be the deadliest documented infectious disease. Leveraging a large dataset of 1,013 ancient human genomes and using an approximate Bayesian computation approach, we find that the P1104A variant originated in the common ancestors of West Eurasians ∼30,000 years ago. Furthermore, we show that, following large-scale population movements of Anatolian Neolithic farmers and Eurasian steppe herders into Europe, P1104A has markedly fluctuated in frequency over the last 10,000 years of European history, with a dramatic decrease in frequency after the Bronze Age. Our analyses indicate that such a frequency drop is attributable to strong negative selection starting ∼2,000 years ago, with a relative fitness reduction on homozygotes of 20%, among the highest in the human genome. Together, our results provide genetic evidence that TB has imposed a heavy burden on European health over the last two millennia.

Research on Tuberculosis in Nazi Germany and the Cruelest Medical Experiments on Jewish Children: An Observational Review.

BACKGROUND: Germany was a scientifically advanced country in the 19th and early 20th centuries, particularly in medicine, with a major interest in research and the treatment of tuberculosis. From 1933 until 1945, Nazi Germany perverted scientific research through criminal experimentations on captured prisoners of war and on "subhumans" by scientifically untrained, but politically driven, staff. This article exposes a series of failed experiments on tuberculosis in adults, experiments without scientific validity. Nonetheless, Dr. Kurt Heißmeyer repeated the experiment on Jewish children, who were murdered for the sake of personal academic ambition. It is now 75 years since liberation and the murdered children must be remembered. This observational review raises questions of medical and ethical values.

Human major infections: Tuberculosis, treponematoses, leprosy-A paleopathological perspective of their evolution.

The key to evolution is reproduction. Pathogens can either kill the human host or can invade the host without causing death, thus ensuring their own survival, reproduction and spread. Tuberculosis, treponematoses and leprosy are widespread chronic infectious diseases whereby the host is not immediately killed. These diseases are examples of the co-evolution of host and pathogen. They can be well studied as the paleopathological record is extensive, spanning over 200 human generations. The paleopathology of each disease has been well documented in the form of published synthetic analyses recording each known case and case frequencies in the samples they were derived from. Here the data from these synthetic analyses were re-analysed to show changes in the prevalence of each disease over time. A total of 69,379 skeletons are included in this study. There was ultimately a decline in the prevalence of each disease over time, this decline was statistically significant (Chi-squared, p<0.001). A trend may start with the increase in the disease's prevalence before the prevalence declines, in tuberculosis the decline is monotonic. Increase in skeletal changes resulting from the respective diseases appears in the initial period of host-disease contact, followed by a decline resulting from co-adaptation that is mutually beneficial for the disease (spread and maintenance of pathogen) and host (less pathological reactions to the infection). Eventually either the host may become immune or tolerant, or the pathogen tends to be commensalic rather than parasitic.

Verification of tuberculosis infection among Vác mummies (18th century CE, Hungary) based on lipid biomarker profiling with a new HPLC-HESI-MS approach.

Tuberculosis (TB) was a large burden of infections that peaked during the 19th century in Europe. Mummies from the 18th century CE, discovered in the crypt of a church at Vác, Hungary, had high TB prevalence, as revealed by amplification of key fragments of TB DNA and genome-wide TB analysis. Complementary methods are needed to confirm these diagnoses and one approach uses the identification of specific lipid biomarkers, such as TB mycocerosic acids (MCs). Previously, MC derivatives were profiled by specialised gas chromatography-mass spectrometry (GC-MS), so an alternative more direct approach has been developed. Underivatized MCs are extracted and analysed by high-performance liquid chromatography linked to a mass spectrometer, in heated electrospray ionisation mode (HPLC-HESI-MS). The method was validated using representatives of the Mycobacterium tuberculosis complex and other mycobacteria and tested on six Vác mummy cases, previously considered positive for TB infection. Analysing both rib and soft tissue samples, four out of six cases gave profiles of main C32 and major C29 and C39 mycocerosates correlating well with those of M. tuberculosis. Multidisciplinary methods are needed in the diagnosis of ancient tuberculosis; this new protocol accesses important confirmatory evidence, as demonstrated by the confirmation of TB in the Vác mummies.