Leprosy in medieval Denmark: Exploring life histories through a multi-tissue and multi-isotopic approach.

OBJECTIVES: By focusing on two Danish leprosaria (Naestved and Odense; 13th-16th c. CE) and using diet and origin as proxies, we follow a multi-isotopic approach to reconstruct life histories of patients and investigate how leprosy affected both institutionalized individuals and the medieval Danish community as a whole. MATERIALS AND METHODS: We combine archaeology, historical sources, biological anthropology, isotopic analyses (δ13 C, δ15 N, δ34 S, 87 Sr/86 Sr) and radiocarbon dating, and further analyze bones with different turnover rates (ribs and long bones). RESULTS: The δ13 C, δ15 N and δ34 S results indicate a C3 terrestrial diet with small contributions of marine protein for leprosy patients and individuals from other medieval Danish sites. A similar diet is seen through time, between males and females, and patients with and without changes on facial bones. The isotopic comparison between ribs and long bones reveals no significant dietary change. The δ34 S and 87 Sr/86 Sr results suggest that patients were local to the regions of the leprosaria. Moreover, the radiocarbon dates show a mere 50% agreement with the arm position dating method used in Denmark. CONCLUSIONS: A local origin for the leprosy patients is in line with historical evidence, unlike the small dietary contribution of marine protein. Although only 10% of the analyzed individuals have rib/long bone offsets that undoubtedly show a dietary shift, the data appear to reveal a pattern for 25 individuals (out of 50), with elevated δ13 C and/or δ15 N values in the ribs compared to the long bones, which points toward a communal type of diet and reveals organizational aspects of the institution.

Ancient genomes reveal a high diversity of Mycobacterium leprae in medieval Europe.

Studying ancient DNA allows us to retrace the evolutionary history of human pathogens, such as Mycobacterium leprae, the main causative agent of leprosy. Leprosy is one of the oldest recorded and most stigmatizing diseases in human history. The disease was prevalent in Europe until the 16th century and is still endemic in many countries with over 200,000 new cases reported annually. Previous worldwide studies on modern and European medieval M. leprae genomes revealed that they cluster into several distinct branches of which two were present in medieval Northwestern Europe. In this study, we analyzed 10 new medieval M. leprae genomes including the so far oldest M. leprae genome from one of the earliest known cases of leprosy in the United Kingdom-a skeleton from the Great Chesterford cemetery with a calibrated age of 415-545 C.E. This dataset provides a genetic time transect of M. leprae diversity in Europe over the past 1500 years. We find M. leprae strains from four distinct branches to be present in the Early Medieval Period, and strains from three different branches were detected within a single cemetery from the High Medieval Period. Altogether these findings suggest a higher genetic diversity of M. leprae strains in medieval Europe at various time points than previously assumed. The resulting more complex picture of the past phylogeography of leprosy in Europe impacts current phylogeographical models of M. leprae dissemination. It suggests alternative models for the past spread of leprosy such as a wide spread prevalence of strains from different branches in Eurasia already in Antiquity or maybe even an origin in Western Eurasia. Furthermore, these results highlight how studying ancient M. leprae strains improves understanding the history of leprosy worldwide.

Learning from the past in the COVID-19 era: rediscovery of quarantine, previous pandemics, origin of hospitals and national healthcare systems, and ethics in medicine.

After the dramatic coronavirus outbreak at the end of 2019 in Wuhan, Hubei province, China, on 11 March 2020, a pandemic was declared by the WHO. Most countries worldwide imposed a quarantine or lockdown to their citizens, in an attempt to prevent uncontrolled infection from spreading. Historically, quarantine is the 40-day period of forced isolation to prevent the spread of an infectious disease. In this educational paper, a historical overview from the sacred temples of ancient Greece-the cradle of medicine-to modern hospitals, along with the conceive of healthcare systems, is provided. A few foods for thought as to the conflict between ethics in medicine and shortage of personnel and financial resources in the coronavirus disease 2019 era are offered as well.

Leprosy in skulls from the Paris Catacombs.

Background: The Paris Catacombs contain the remains of approximately 6 million people dating back to the 15th century, when leprosy was endemic in France.Aims: The aim of this palaeopathological study was to identify the presence of leprosy in skulls from the Paris Catacombs.Subjects and methods: Macroscopic examination of skulls in situ for bone changes secondary to oronasal soft tissue infection by leprosy. Skulls were categorised as having "probable" signs of leprosy if they had an enlarged nasal (pyriform) aperture, resorption of the anterior nasal spine, and resorption of the alveolar processes of maxilla, and as having "possible" signs of leprosy if they met one of these three criteria.Results: Skulls from 123 sections within the Catacombs (approximately 1500 remains in total) were triaged, with 367 skulls identified as suitable for examination. Of these, 74 had central facial bone alterations/abnormalities and underwent detailed examination, yielding 0.5% (2/367) classified as having probable, and 5.7% (21/367) possible signs of leprosy.Conclusions: The proportion of skulls with probable signs of leprosy gives an approximate estimate (0.5%) for the prevalence of this disease in the population of Paris (or districts of Paris) during the 15-18th centuries.

Tuberculosis and leprosy associated with historical human population movements in Europe and beyond - an overview based on mycobacterial ancient DNA.

Context: Tuberculosis and leprosy are readily recognised in human remains due to their typical palaeopathology. Both Mycobacterium tuberculosis (MTB) and Mycobacterium leprae (ML) are obligate pathogens and have been detected in ancient human populations. Objective: To demonstrate historical tuberculosis and leprosy cases in Europe and beyond using molecular methods, as human populations are associated with different mycobacterial genotypes. Methods: MTB and ML ancient DNA (aDNA) has been detected by DNA amplification using PCR, or by whole genome sequencing. Mycobacterial cell wall lipids also provide specific markers for identification. Results: In 18th century Hungary, the European indigenous MTB genotype 4 strains have been found. However, many individuals were co-infected with up to three MTB sub-genotypes. In 8th-14th century Europe significant differences in ML genotypes were found between northwest Europe compared with central, southern, or eastern Europe. In addition, several co-infections of MTB and ML were detected in historical samples. Conclusion: Both MTB and ML strain types differ between geographically separate populations. This is associated with ancient human migration after an evolutionary bottleneck and clonal expansion. The absence of indigenous leprosy in Europe today may be due to the greater mortality of tuberculosis in individuals who are co-infected with both organisms.

Lessons From Leprosy: Peripheral Neuropathies and Deformities in Chronic Demyelinating Diseases.

In light of the World Health Organization's push to accelerate progress toward a leprosy-free world by 2020, it is fitting to look back on the evolution of progress in treating lepromatous neuropathy and limb deformities. To date, no surgeon has had as great an impact on the understanding and treatment of this disease as Dr Paul Brand. Before Dr Brand's accomplishments, few surgeons participated in the management of the deformed leprous patient. By challenging conventional beliefs, Dr Brand revealed that many of the deformities associated with leprosy were in fact caused by nerve damage and subsequent limb anesthesia. His pioneering work centered on tendon transfers to provide hand and foot mobility to leprous patients, revolutionizing the surgical management of this patient population and restoring functionality to the lives of otherwise stigmatized and functionally handicapped individuals. In the process, he provided us with the surgical principles and techniques that we still apply today. Because of its predilection for the peripheral nervous system, leprosy also provides an excellent opportunity to investigate mechanisms of demyelination and chronic nerve degeneration in nonacute peripheral neuropathies. Processes underlying demyelination of infectious, traumatic, and genetic etiologies overlap and precede the onset of acute neuronal derangement. Glial pathology has been shown to be a common pathological element in leprosy, Charcot-Marie-Tooth type I, multiple sclerosis, and chronic nerve compression injury. The aim of this article is to provide an overview of lepromatous neuropathy with its subsequent deformities as it relates to the pathophysiology, surgical management, and potential therapeutic targets of other modern peripheral neuropathies.

Arresting Leprosy: Therapeutic Outcomes Besides Cure.

This essay focuses on the use of the concept of "arrest" in Hansen's disease (leprosy) in the United States in the early to middle part of the 20th century, as well as the transformations the concept underwent with the arrival of sulfone drugs and the implications of these changes for patients and public health officers. An "arrest" was a therapeutic outcome characterized by a long course of treatment, noncontagiousness, a very small chance of reactivation, and a need for postdischarge maintenance that depended on sociomedical infrastructures beyond the clinic as well as self-imposed lifestyle limitations. The concept of disease arrest shows that experts and laypeople alike have valued therapeutic outcomes other than "cure" that signal certain optimal therapeutic milestones, despite the practical difficulties they imply and despite the fact that they do not promise a return to a pre-illness stage.

Leprosy's Untainted Child.

In the face of an obdurate disease, the Mission to Lepers made a virtue out of "saving" children from leprosy and from paganism by separating them from their parents so that they became a source of publicity, sponsorship, and fund-raising. This policy transformed a benevolent work of mercy into a professional one, for it soon became clear that children separated from their parents did not develop leprosy. Consequently, the asylum became a site where scientific conclusions were made about the transmission of the disease, and the authority of the mission was enhanced at international medical conferences. This nascent professionalism became sufficient for the Philippines to also be persuaded to remove children from their leprosy-infected parents. In turn, Culion-based research on the observations of children ensured the authority of the American and Philippine doctors in informing decisions made by the League of Nations and later the World Health Organization.

The effect of leprotic infection on the risk of death in medieval rural Denmark.

INTRODUCTION: Paleopathological studies of leprosy in Danish skeletal collections show that many individuals suffered from this stigmatized disease during the Middle Ages. This study examines the risk of death associated with leprotic infection in individuals from the Danish rural cemetery of Øm Kloster (AD 1172-1536). Specifically, we modeled the influence of leprotic infection on age-specific mortality accounting also for sex and social status (lay person / monastic). MATERIALS AND METHODS: The sample consisted of 311 adult individuals from the Øm Kloster skeletal collection housed at the Institute of Forensic Medicine, University of Southern Denmark (ADBOU). We modeled morbidity and mortality using a three-state illness-death model with the following parameterizations for the three transition hazards: (1) nonlesioned to lesioned: constant; (2) nonlesioned to dead: Gompertz-Makeham; and (3) lesioned to dead: Gompertz-Makeham, directly proportional to the hazard of the well to dead transition. RESULTS: The mortality hazard of lesioned individuals exceeded that of nonlesioned individuals by a factor of 1.4 (40%) across all individuals, 1.7 for females, 1.0 for males, 1.3 for lay persons, and 1.7 for monastics. Overall, 15% of the sample died with skeletal manifestations of leprosy, though it is likely that a higher percentage of the population carried the bacterium. DISCUSSION: This study improves understanding of past health and population dynamics focusing on a chronic infectious disease. The methods employed could informatively be applied to larger analyses of community health from skeletal collections by incorporating more than one disease into the multistate model and inferring individual frailty using various skeletal markers.

Leprosy in a Lombard-Avar cemetery in central Italy (Campochiaro, Molise, 6th-8th century AD): ancient DNA evidence and demography.

BACKGROUND: The study of past infectious diseases increases knowledge of the presence, impact and spread of pathogens within ancient populations. AIM: Polymerase chain reaction (PCR) was used to examine bones for the presence of Mycobacterium leprae ancient DNA (aDNA) as, even when leprosy is present, bony changes are not always pathognomonic of the disease. This study also examined the demographic profile of this population and compared it with two other populations to investigate any changes in mortality trends between different infectious diseases and between the pre-antibiotic and antibiotic eras. SUBJECTS AND METHODS: The individuals were from a site in Central Italy (6th-8th CE) and were examined for the presence of Mycobacterium leprae aDNA. In addition, an abridged life mortality table was constructed. RESULTS: Two individuals had typical leprosy palaeopathology, and one was positive for Mycobacterium leprae aDNA. However, the demographic profile shows a mortality curve similar to that of the standard, in contrast to a population that had been subjected to bubonic plague. CONCLUSIONS: This study shows that, in the historical population with leprosy, the risk factors for health seem to be constant and distributed across all age classes, similar to what is found today in the antibiotic era. There were no peaks of mortality equivalent to those found in fatal diseases such as the plague, probably due to the long clinical course of leprosy.

A synopsis of the history of Hansen's disease.

Leprosy is a contagious infectious disease caused by the bacillus Mycobacterium leprae. This microorganism was discovered by Dr. Gerhard Hansen, and the illness was then baptized as Hansen's disease. For a long time, Hansen's disease was thought to be hereditary-a curse or a punishment from God. The disease affects skin and nerves and can cause severe damage. Due to its destructive effects, leprosy has caused fear, segregation, and prejudice in all societies since Biblical times. Patients with Hansen's disease have not been treated humanely around the world throughout the ages. This article is a summary of curious and interesting facts about the history and cultural aspects of Hansen's disease, which has chastised humanity for centuries. These facts are about the discovery of the disease, its propagation, the evolution of treatments, and the prejudice of society towards patients.

Humanitarian quarantine in practice: medicine, religion and leprosy in New Caledonia.

Medicine and religion worked in close synchronisation during the leprosy outbreak of New Caledonia (1890-1950). Once isolation of leprosy-affected people became mandatory doctors and missionaries came together to promote a particular form of medical practice that tied charitable zeal with cutting-edge medical research, developing a sophisticated set of medical practices that catered for the soul as well as the body. Such practices went hand-in-hand with ideas developed by doctors in the earlier stages of the epidemic about the way in which the disease had entered the Kanak (local Melanesian) population. Doctors and missionaries admitted that immoral colonial channels had upset the delicate balance of local social and biological rhythms. Yet they also believed that the highly contagious nature of the outbreak was linked to the inferior state of Kanak. This paper aims to highlight the way in which the leprosaria system in New Caledonia represented a double-edged moral high-ground within the French medical colonial narrative. It tracks the complex way in which emotionally charged arguments about contagion, science and spirituality constructed an ideology of humanitarian quarantine which was used to justify a highly aggressive form of medical biocontrol.

A Modern History of 'Imperial Medicine' Surrounding Hansen's Disease: Strategies to Manage Public Opinion in Modern Japanese Media.

The purpose of this study is to understand the reality of imperial medicine by exploring the strategic attitude of the Japanese authority targeting the public who were not patients of Hansen's disease. For this purpose, this study examines the mass media data related to Hansen's disease published in Korea and Japan during the Japanese colonial rule. Research on Hansen's disease can be divided into medical, sociohistorical, social welfare, and human rights approach. There are medical studies and statistics on the dissemination of medical information about Hansen's disease and management measures, the history of the management of the disease, guarantee of the rights of the patients and the welfare environment, and studies on the autobiographical, literary writings and oral statements on the life and psychological conflicts of the patients. Among existing research, the topics of the study on Hansen's disease under the Japanese colonial rule include the history of the Sorokdo Island Sanatorium, investigation on the forced labor of the patients in the island, human rights violations against the patients, oral memoirs of the patients and doctors who practiced at that time. All of these studies are important achievements regarding the research on the patients. An important study of Hansen's disease in modern Japan is the work of Hujino Utaka, which introduces the isolation of and discrimination against the patients of Hansen's disease. Hujino Utaka's study examines the annihilation of people with infectious diseases in Japan and its colonies by the imperial government, which was the consequence of the imperial medical policies, and reports on the isolation of Hansen's disease patients during the war. Although these researches are important achievements in the study of Hansen's disease in modernity, their focus has mainly been on the history of isolation and exploitation in the Sorokdo Island Sanatorium and discrimination against the patients within the sanatorium, which was controlled by the director of the sanatorium. Consequently, the research tends to perceive the problem within the frame of antagonism between the agent of imperialism and the victims of exploitation by the hands of imperialism. Hence, it has limitations in that it has not fully addressed the problem of the people who were not Hansen's disease patients and as such, existed somewhere in between the two extremes in the process of administering medicine under the imperial rule. The purpose of this study is to identify the direction of imperial medicine in the history of Hansen's disease in Japan and to comprehend the characteristics of policy on Hansen's disease developed by Mitsuda Kensuke, who was behind the policy of imperial medicine, and examine the process of imperial medicine reaching out to the people (of Japan and its colonies). To achieve the goal, this study explores how the agent of imperial medicine gain the favor the public, who are not Hansen's disease patients, by means of the mass media. Specifically, this paper examines data in the Japanese language related to Korean patients of Hansen's disease including the mass media data on Hansen's disease in the source book titled The Collection of Data on Hansen's Disease in Joseon under the Colonial Rule(8 volumes) compiled by Takio Eiji, which has not been studied until now. It also reviews the cultural and popular magazines published in Japan and Joseon at that time.

The decline of leprosy in the Republic of Korea; patterns and trends 1977-2013.

BACKGROUND: Though the World Health Organization declared the 'elimination of leprosy as public health problem' in 2000, the disease remains endemic in many countries. Current trends in incidence of infection and disease are unclear. METHODS: Data on leprosy prevalence between 1977-2013 and data on new leprosy cases detected in the Republic of Korea between 1989-2013 were analysed by age, sex, clinical types, mode of detection, family history, disability grading and geographical distribution. RESULTS: Both prevalence and incidence have declined greatly. There has been a shift to an increased proportion of multibacillary disease, and older age groups, consistent with a dramatic decrease in infection transmission in recent decades. An increase in proportion of cases with family history of disease is consistent with these declines. There is evidence that declines in infection and disease have been greater in the north of the country, as revealed in patterns by place of birth over time. Cases in immigrants now form a substantial proportion of leprosy disease in the Republic of Korea. CONCLUSIONS: Leprosy has declined dramatically in the Republic of Korea in recent decades, and transmission of M. leprae may have effectively stopped. There remains a burden of care for individuals whose disease developed in the past, and there may be some additional newly detected cases among immigrants and among older individuals who acquired autochthonous infections decades ago.

First genetic evidence of leprosy in early medieval Austria.

Leprosy used to be a widespread, dreaded disease in Europe during the middle ages, and it still remains an important health problem in some parts of the world today. Herein, we present data on the earliest 'Austrian' (an adult female from the early medieval period) proven to have suffered from leprosy. Manifestations of the disease were first identified during a systematic screening of pathological changes in skeletons recovered from an archaeological site in Pottenbrunn (Lower Austria). In the present study, DNA extracts from selected cranial and postcranial bone samples were investigated using polymerase chain reaction primers specific to the Mycobacterium leprae (M. leprae) repetitive element (RLEP). M. leprae traces were detected in extracts from nasal and palatine bones. Sequence analysis of informative polymorphic sites supports previous reports indicating that European M. leprae strains fall into single nucleotide polymorphism group 3. In summary, these findings put Austria on the map of confirmed leprosy cases in ancient Europe.

Bone Changes in an Italian Ancient Human Skeleton--Possibly Caused by Leprosy.

Leprosy is an infectious disease caused by Mycobacterium leprae and Mycobacterium lepromatosis. In the last stage it can afflict the skeleton with a series of specific and non-specific bone changes. The possibility of studyingthe skeleton of an individual who lived in the pre-antibiotic era (Roman period) with skeletal changes in the rhino-maxillary region and hand and foot bones, permitted skeletal lesions to be analyzed directly. In addition, the localization and the complexity of the bony lesions could be attributed to the presence of leprosy. The importance of this approach was the possibility to verify the nature and typology of the primary and secondary bone changes in leprosy in absence of clinical therapy.