Bioarchaeological investigation of individuals with suspected multibacillary leprosy from the mediaeval leprosarium of St Mary Magdalen, Winchester, Hampshire, UK.

Introduction. We have examined four burials from the St Mary Magdalen mediaeval leprosarium cemetery in Winchester, Hampshire, UK. One (Sk.8) was a male child, two (Sk.45 and Sk.52) were adolescent females and the fourth (Sk.512) was an adult male. The cemetery was in use between the 10th and 12th centuries. All showed skeletal lesions of leprosy. Additionally, one of the two females (Sk.45) had lesions suggestive of multi-cystic tuberculosis and the second (Sk.52) of leprogenic odontodysplasia (LO), a rare malformation of the roots of the permanent maxillary incisors.Gap statement. Relatively little is known of the manifestations of lepromatous leprosy (LL) in younger individuals from the archaeological record.Aims and Methodology. To address this, we have used ancient DNA testing and osteological examination of the individuals, supplemented with X-ray and microcomputed tomography (micro-CT) scan as necessary to assess the disease status.Results and Conclusions. The presence of Mycobacterium leprae DNA was confirmed in both females, and genotyping showed SNP type 3I-1 strains but with a clear genotypic variation. We could not confirm Mycobacterium tuberculosis complex DNA in the female individual SK.45. High levels of M. leprae DNA were found within the pulp cavities of four maxillary teeth from the male child (Sk.8) with LO, consistent with the theory that the replication of M. leprae in alveolar bone may interfere with root formation at key stages of development. We report our biomolecular findings in these individuals and review the evidence this site has contributed to our knowledge of mediaeval leprosy.

The Centenary of the Leprosy Relief Association (Lepra)-a moment for celebration and reflection†.

The year 2024 is the Centenary of the foundation of the Leprosy Relief Association (Lepra), formerly the British Empire Leprosy Relief Association (BELRA). The name of the organization changed to the LEProsy Relief Association (LEPRA) in 1976 but has been known as Lepra since 2008. Over the years it has worked closely with members and office holders of the Royal Society of Tropical Medicine and Hygiene. Its work has encompassed activities from the earliest initiatives to ensure appropriate living conditions for those with the disease to the development of leprosy chemotherapy. However, this has now evolved into a strong partnership between the UK- and India-based Lepra hubs, which are carrying out research and public health initiatives ranging from elimination of prejudice against those with leprosy to adopting the recently launched WHO programme for skin NTDs to facilitate integrated control and management regimens. The fight against leprosy has always been a partnership between a wide variety of disease-specific NGOs, health-care workers and international health agencies. The story of Lepra illustrates the central role of these partnerships and national as well as international collaboration.

COVID-19 vaccination and leprosy-A UK hospital-based retrospective cohort study.

BACKGROUND: Individuals with leprosy are at risk of leprosy reactions, T-cell mediated immunological complications, which lead to nerve function impairment. Leprosy reactions require systemic immunosuppression which is a risk factor for severe COVID-19. Vaccination for SARS-CoV-2 infection is recommended in the UK and became widely available in 2021 with individuals at increased risk of severe disease, including the immunosuppressed, prioritised. Vaccines for SARS-CoV-2 may provoke a T cell response. The latter poses a theoretical risk of provoking an immunological response to latent Mycobacterium leprae infection leading to clinical disease or in those with clinical disease triggering a leprosy reaction. BCG vaccination is associated with the development of leprosy in a small proportion of healthy contacts of people with leprosy within twelve weeks of administration. BCG causes a Th1 immune response. METHODOLOGY/PRINCIPAL FINDINGS: We performed a retrospective cohort study to determine the SARS-CoV-2 vaccination status of individuals diagnosed with leprosy attending the Leprosy Clinic in 2021 and whether any had developed leprosy or experienced a new leprosy reaction within twelve weeks of receiving a dose of a SARS-CoV-2 vaccine. The electronic patient records were used to retrieve data. Fifty-two individuals with leprosy attended the clinic in 2021 of which five people were newly diagnosed with leprosy. Thirty-seven (71%) were male and the median age was 48.5 years old (Range 27-85 years). Eight (15.4%) individuals were taking multi-drug therapy (MDT) and eight (15.4%) had completed MDT within three years of the study. Twenty-two (41.5%) individuals were prescribed a systemic immunosuppressant drug during 2021. Ten (18.9%) individuals have one or more risk factors for severe COVID-19. The SARS-CoV-2 vaccination status of fifty (96%) were recorded of which forty-nine were vaccinated (98%). One individual had declined vaccination. One individual was diagnosed with borderline tuberculoid (BT) leprosy having developed red skin lesions with reduced sensation (which increased in size and number) and thickened peripheral nerves one week after a second dose of BNT162b2 vaccine. Another individual who had completed MDT more than three years earlier developed red plaques and tender thickened nerves consistent with a leprosy Type 1 reaction eight weeks after a single dose of BNT162b2 vaccine (having received two doses of CoronaVac vaccine three months earlier). CONCLUSIONS/SIGNIFICANCE: The development of BT leprosy and a Type 1 reaction in another individual shortly after a dose of BNT162b2 vaccine may be associated with vaccine mediated T cell responses. The benefits of vaccination to reduce the risk of severe COVID-19 outweigh these unwanted events but data from leprosy endemic countries may provide further information about potential adverse effects of augmented T cell responses in individuals with leprosy or latent M. leprae infection.

Ancient DNA confirmation of lepromatous leprosy in a skeleton with concurrent osteosarcoma, excavated from the leprosarium of St. Mary Magdalen in Winchester, Hants., UK.

To establish a biological profile and disease aetiologies for one of four burials recovered during a Time Team dig at the St. Mary Magdalen leprosarium, Winchester, UK in AD 2000. Osteological techniques were applied to estimate age at death, biological sex, stature and pathology. Visual assessment of the material was supplemented by radiographic examination. Evidence for leprosy DNA was sought using ancient DNA (aDNA) analysis. The remains are those of a male individual excavated from a west-east aligned grave. The skeleton shows signs of two pathologies. Remodelling of the rhino-maxillary area and degenerative changes to small bones of the feet and reactive bone on the distal lower limbs suggest a multibacillary form of leprosy, whereas the right tibia and fibula show the presence of a primary neoplasm identified as an osteosarcoma. The aDNA study confirmed presence of Mycobacterium leprae in several skeletal elements, and the strain was genotyped to the 3I lineage, one of two main SNP types present in mediaeval Britain and ancestral to extant strains in America. This is a rare documentation of leprosy in association with a primary neoplasm.

Investigations associated with the 2020/21 highly pathogenic avian influenza epizootic in wild birds in Great Britain.

This focus article has been prepared by Paul Duff, Paul Holmes, James Aegerter, Cat Man, Ed Fullick, Scott Reid, Fabian Lean, Alex Núñez, Rowena Hansen, Joanna Tye, Lévon Stephan and Ian Brown of the APHA and Caroline Robinson of SRUC.

DIAGNOSING AND CATEGORIZING LEPROSY IN LIVE EURASIAN RED SQUIRRELS (SCIURUS VULGARIS) FOR MANAGEMENT, SURVEILLANCE, AND TRANSLOCATION PURPOSES.

The presence of Mycobacterium lepromatosis and Mycobacterium leprae in Eurasian red squirrel (Sciurus vulgaris, ERS) carcasses throughout the British Isles, and leprosy as a disease, have recently been reported using histological and molecular diagnostic methods. In 2016, the first longitudinal study of ERS affected by leprosy was initiated. One of the main challenges was the reliable diagnosis of leprosy in live ERS, which is important for (a) welfare and case management and (b) surveillance or pretranslocation screening efforts. We explored diagnostic methods ranging from detailed clinical assessment and informative categorization of observed lesions, thermal imaging, serology (antiphenolic glycolipid-I antibody [αPGL-I] detection) to molecular methods (polymerase chain reaction [PCR]). For PCR the ear was established as the optimal sampling site. Based on the experiences from this 2-yr study we propose an objective categorization system for clinical lesions and a diagnostic framework for the combination of the diagnostic tools we found to be effective in live ERS: clinical assessment, αPGL-I serology, and PCR. Thermal imaging did not offer additional information for leprosy diagnostics in ERS. We propose an amended definition of leprosy lesions in ERS as "skin areas of local hair loss, in which a firm-rubbery, glossy swelling develops, that may ulcerate" and standardized terminology for describing ERS leprosy status. The information presented forms the basis of a consistent, reliable diagnostic and reporting system for leprosy cases in ERS.

PTPRG is an ischemia risk locus essential for HCO3--dependent regulation of endothelial function and tissue perfusion.

Acid-base conditions modify artery tone and tissue perfusion but the involved vascular-sensing mechanisms and disease consequences remain unclear. We experimentally investigated transgenic mice and performed genetic studies in a UK-based human cohort. We show that endothelial cells express the putative HCO3--sensor receptor-type tyrosine-protein phosphatase RPTPγ, which enhances endothelial intracellular Ca2+-responses in resistance arteries and facilitates endothelium-dependent vasorelaxation only when CO2/HCO3- is present. Consistent with waning RPTPγ-dependent vasorelaxation at low [HCO3-], RPTPγ limits increases in cerebral perfusion during neuronal activity and augments decreases in cerebral perfusion during hyperventilation. RPTPγ does not influence resting blood pressure but amplifies hyperventilation-induced blood pressure elevations. Loss-of-function variants in PTPRG, encoding RPTPγ, are associated with increased risk of cerebral infarction, heart attack, and reduced cardiac ejection fraction. We conclude that PTPRG is an ischemia susceptibility locus; and RPTPγ-dependent sensing of HCO3- adjusts endothelium-mediated vasorelaxation, microvascular perfusion, and blood pressure during acid-base disturbances and altered tissue metabolism.

Restricted blood flow in the heart or brain can deprive these vital organs of oxygen, thereby causing a heart attack or stroke. However, the body has compensatory mechanisms to mitigate damage: if the blood flow is reduced in one blood vessel, acidic waste accumulates locally. This causes nearby blood vessels to widen and increase the oxygen supply. Although scientists first observed this process 140 years ago, they have not yet devised a way to use it for treatment of heart attack or stroke. Now, Hansen et al. discovered that a protein called RPTPγ, which is found on the lining of blood vessels, could be a good target for drugs intended to reduce the consequences of heart attacks and strokes. The protein RPTPγ has a similar structure to other proteins that bind bicarbonate, an important ion that buffers acids in the body. RPTPγ can also trigger signals to nearby cells, which suggests that the protein can monitor bicarbonate levels in the blood and tissue and alert blood vessels of the need to widen. Hansen et al. found that the blood vessels of mice that lacked RPTPγ were unable to widen when needed. Moreover, mice without RPTPγ experienced abnormal changes in blood pressure and blood flow to the brain when oxygen consumption was elevated or pH was disrupted. Hansen et al. further analyzed genetic and health data from nearly 50,000 individuals in the UK Biobank. These analyses revealed that people with genetic changes that render RPTPγ ineffective are at higher risk of having a heart attack or stroke. People with these genetic variants also have reduced heart pumping ability. The experiments suggest that a lack of functional RPTPγ affects an individual's ability to adjust local blood flow in response to acid-base disturbances and oxygen deficits, increasing the risk of a heart attack or stroke. This information may help scientists develop new ways to prevent or treat heart attacks and strokes, or to treat other conditions like cancer, where pH is disturbed.

Lack of evidence for the presence of leprosy bacilli in red squirrels from North-West Europe.

Leprosy is a human infectious disease caused by Mycobacterium leprae or Mycobacterium lepromatosis that can also occur in animals and even manifest as zoonosis. Recently, both mycobacteria were detected in red squirrels (Sciurus vulgaris) from the British Isles. To further explore the presence of leprosy bacilli in North-West Europe, we screened Belgian and Dutch squirrels. Tissue samples from 115 animals tested by qPCR were negative for both pathogens. No molecular or pathological evidence was found of the presence of these zoonotic pathogens in North-West Europe.

Differential diagnosis of negated avian notifiable disease cases in Great Britain.

This focus article has been prepared by David Welchman, veterinary lead of the APHA Avian Expert Group, Rowena Hansen, veterinary lead for avian virology at APHA Weybridge, and Alex Schock, team leader of the diagnostic and consultant avian pathology services at APHA Lasswade.

Epidemiology of viral hepatitis in Somalia: Systematic review and meta-analysis study.

AIM: To provide a clear understanding of viral hepatitis epidemiology and their clinical burdens in Somalia. METHODS: A systematic review and meta-analysis was conducted as Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A comprehensive literature search of published studies on viral hepatitis was performed from 1977-2016 in PubMed, Google Scholar, Science Direct, World Health Organization African Index Medicus and the Africa Journals Online databases, as well as on the Ministry of Health website. We also captured unpublished articles that were not available on online systems. RESULTS: Twenty-nine studies from Somalia and Somali immigrants (United Kingdom, United States, Italy, Libya) with a combined sample size for each type of viral hepatitis [hepatitis A virus (HAV): 1564, hepatitis B virus (HBV): 8756, hepatitis C virus (HCV): 6257, hepatitis D virus (HDV): 375 and hepatitis E virus (HEV): 278] were analyzed. The overall pooled prevalence rate of HAV was 90.2% (95%CI: 77.8% to 96%). The HAV prevalence among different age groups was as follows: < 1 year old, 61.54% (95%CI: 40.14% to 79.24%); 1-10 years old, 91.91% (95%CI: 87.76% to 94.73%); 11-19 years old, 96.31% (95%CI: 92.84% to 98.14%); 20-39 years old, 91.3% (95%CI: 83.07% to 95.73%); and > 40 years old, 86.96% (95%CI: 75.68% to 93.47%). The overall pooled prevalence of HBV was 18.9% (95%CI: 14% to 29%). The overall pooled prevalence among subgroups of HBV was 20.5% (95%CI: 5.1% to 55.4%) in pregnant women; 5.7% (95%CI: 2.7% to 11.5%) in children; 39.2% (95%CI: 33.4% to 45.4%) in patients with chronic liver disease, including hepatocellular carcinoma (HCC); 7.7% (95%CI: 4.2% to 13.6%), 12.4% (95%CI: 6.3% to 23.0%) and 11.8% (95%CI: 5.3% to 24.5%) in age groups < 20 years old, 20-39 years old and > 40 years old, respectively. The HBV prevalence among risk groups was 20% (95%CI: 7.19% to 44.64%) in female prostitutes, 21.28% (95%CI: 7.15% to 48.69%) in hospitalized adults, 5.56% (95%CI: 0.99% to 25.62%) in hospitalized children, 60% (95%CI: 31.66% to 82.92%) in patients with acute hepatitis, 33.55% (95%CI: 14.44% to 60.16%) in patients with ancylostomiasis, 12.34% (95%CI: 7.24% to 20.26%) in patients with leprosy and 20.19% (95%CI: 11.28% to 33.49%) in schistosomiasis patients. The overall pooled prevalence of HCV was estimated as 4.84% (95%CI: 3.02% to 7.67%). The prevalence rates among blood donors, risk groups, children and patients chronic liver disease (including HCC) was 0.87% (95%CI: 0.33% to 2.30%), 2.43% (95%CI: 1.21% to 4.8%), 1.37% (95%CI: 0.76% to 2.46%) and 29.82% (95%CI: 15.84% to 48.98%), respectively. The prevalence among genotypes of HCV was 21.9% (95%CI: 15.36% to 30.23%) in genotype 1, 0.87% (95%CI: 0.12% to 5.9%) in genotype 2, 25.21% (95%CI: 18.23% to 33.77%) in genotype 3, 46.24% (95%CI: 37.48% to 55.25%) in genotype 4, 2.52% (95%CI: 0.82% to 7.53%) in genotype 5, and 1.19% (95%CI: 0.07% to 16.38%) in genotype 6. The overall pooled prevalence of HDV was 28.99% (95%CI: 16.38% to 45.96%). The HDV prevalence rate among patients with chronic liver disease, including HCC, was 43.77% (95%CI: 35.09% to 52.84%). The overall pooled prevalence of HEV was 46.86% (95%CI: 5.31% to 93.28%). CONCLUSION: Our study demonstrates a high prevalence of all forms of viral hepatitis in Somalia and it also indicates that chronic HBV was the commonest cause of chronic liver disease. This highlights needs for urgent public health interventions and strategic policy directions to controlling the burden of the disease.

Leprosy in pre-Norman Suffolk, UK: biomolecular and geochemical analysis of the woman from Hoxne.

PURPOSE: A woman's skull, exhibiting features of lepromatous leprosy (LL), was recovered from a garden in Hoxne, Suffolk. The absence of post crania and lack of formal excavation meant that diagnosis and dating was uncertain. The aim of this research was to confirm the diagnosis using biomolecular means and second, to place it in context with other British leprosy cases using SNP genotyping and radiocarbon dating. METHODOLOGY: Bone from the skull was analysed by ancient DNA (aDNA) methods and subjected to radiocarbon dating. As a result, stable carbon and nitrogen isotope values were produced, both useful for assessing aspects of the woman's diet.Results/Key findings. aDNA confirmed the presence of mycobacterium leprae and genotyping demonstrated an ancestral variant of subtype 3I, the same lineage recently identified in living squirrels in the south of England. Radiocarbon dating revealed the woman lived approximately between 885-1015 AD, providing evidence for endurance of this subtype in East Anglia, having been previously identified as early as the fifth-sixth century (Great Chesterford) and as late as the thirteenth century (Ipswich). CONCLUSIONS: The confirmation of a new pre-Norman leprosy case in East Anglia is of interest as this is where a high proportion of cases are located. Possible factors for this may include preservation and excavation biases, population density, but also connection and trade, possibly of fur, with the continent. Future research on other British LL cases should focus on exploring these aspects to advance understanding of the disease's history, here and on the continent.

"The legacy of thalidomide" - A multidisciplinary meeting held at the University of York, United Kingdom, on September 30, 2016.

BACKGROUND: Between 1957 and 1962 thalidomide was used as a nonaddictive, nonbarbiturate sedative that also was successful in relieving the symptoms of morning sickness in early pregnancy. Infamously, thousands of babies were subsequently born with severe birth defects. The drug is used again, today, to successfully treat leprosy, and tragically, there is a new generation of thalidomide damaged children in Brazil. While the outward damage in babies has been documented, the effects of the damage upon the survivors as they grow up, the lifestyle changes and adaptations required to be made, as well as studies into ageing in survivors, has received little attention and remains understudied. METHODS: A unique multidisciplinary meeting was organized at the University of York bringing together thalidomide survivors, clinicians, scientists, historians, and social scientists to discuss the past, the current and the future implications of thalidomide. RESULTS: There is still much to learn from thalidomide, from its complex history and ongoing impact on peoples' lives today, to understanding its mechanism/s to aid future drug safety, to help identify new drugs retaining clinical benefit without the risk of causing embryopathy. CONCLUSION: For thalidomide survivors, the original impairments caused by the drug are compounded by the consequences of a lifetime of living with a rare disability, and early onset age-related health problems. This has profound implications for their quality of life and need for health and social care services. It is vital that these issues are addressed in research, and in clinical practice if thalidomide survivors are to "age well". Birth Defects Research 109:296-299, 2017. © 2017 Wiley Periodicals, Inc.

Investigation of a Medieval Pilgrim Burial Excavated from the Leprosarium of St Mary Magdalen Winchester, UK.

We have examined the remains of a Pilgrim burial from St Mary Magdalen, Winchester. The individual was a young adult male, aged around 18-25 years at the time of death. Radiocarbon dating showed the remains dated to the late 11th-early 12th centuries, a time when pilgrimages were at their height in Europe. Several lines of evidence in connection with the burial suggested this was an individual of some means and prestige. Although buried within the leprosarium cemetery, the skeleton showed only minimal skeletal evidence for leprosy, which was confined to the bones of the feet and legs. Nonetheless, molecular testing of several skeletal elements, including uninvolved bones all showed robust evidence of DNA from Mycobacterium leprae, consistent with the lepromatous or multibacillary form of the disease. We infer that in life, this individual almost certainly suffered with multiple soft tissue lesions. Genotyping of the M.leprae strain showed this belonged to the 2F lineage, today associated with cases from South-Central and Western Asia. During osteological examination it was noted that the cranium and facial features displayed atypical morphology for northern European populations. Subsequently, geochemical isotopic analyses carried out on tooth enamel indicated that this individual was indeed not local to the Winchester region, although it was not possible to be more specific about their geographic origin.

The Medicinal Usage and Restriction of Ginseng in Britain and America, 1660-1900.

This article demonstrates the medicinal usage of ginseng in the West from 1660 to 1914. Asian[Korea] ginseng was first introduced into England in the early 17th century, and North American ginseng was found in the early 18th century. Starting from the late 17th century doctors prescribed ginseng to cure many different kinds of ailments and disease such as: fatigue general lethargy, fever, torpidity, trembling in the joints, nervous disorder, laughing and crying hysteria, scurvy, spermatic vessel infection, jaundice, leprosy, dry gripes and constipation, strangury, yellow fever, dysentery, infertility and addictions of alcohol, opium and tobacco, etc. In the mid-18th century Materia Medica began to specify medicinal properties of ginseng and the patent medicines containing ginseng were widely circulated. However, starting in the late 18th century the medicinal properties of ginseng began to be disparaged and major pharmacopoeias removed ginseng from their contents. The reform of the pharmacopoeia, influenced by Linnaeus in botany and Lavoisier in chemistry, introduced nomenclature that emphasized identifying ingredients and active constituents. Western medicine at this period, however, failed to identify and to extract the active constituents of ginseng. Apart from the technical underdevelopment of the period, the medical discourses reveal that the so-called chemical experiment of ginseng were conducted with unqualified materials and without proper differentiation of various species of ginseng.

Red squirrels in the British Isles are infected with leprosy bacilli.

Leprosy, caused by infection with Mycobacterium leprae or the recently discovered Mycobacterium lepromatosis, was once endemic in humans in the British Isles. Red squirrels in Great Britain (Sciurus vulgaris) have increasingly been observed with leprosy-like lesions on the head and limbs. Using genomics, histopathology, and serology, we found M. lepromatosis in squirrels from England, Ireland, and Scotland, and M. leprae in squirrels from Brownsea Island, England. Infection was detected in overtly diseased and seemingly healthy animals. Phylogenetic comparisons of British and Irish M. lepromatosis with two Mexican strains from humans show that they diverged from a common ancestor around 27,000 years ago, whereas the M. leprae strain is closest to one that circulated in Medieval England. Red squirrels are thus a reservoir for leprosy in the British Isles.

Osteological, biomolecular and geochemical examination of an early anglo-saxon case of lepromatous leprosy.

We have examined a 5th to 6th century inhumation from Great Chesterford, Essex, UK. The incomplete remains are those of a young male, aged around 21-35 years at death. The remains show osteological evidence of lepromatous leprosy (LL) and this was confirmed by lipid biomarker analysis and ancient DNA (aDNA) analysis, which provided evidence for both multi-copy and single copy loci from the Mycobacterium leprae genome. Genotyping showed the strain belonged to the 3I lineage, but the Great Chesterford isolate appeared to be ancestral to 3I strains found in later medieval cases in southern Britain and also continental Europe. While a number of contemporaneous cases exist, at present, this case of leprosy is the earliest radiocarbon dated case in Britain confirmed by both aDNA and lipid biomarkers. Importantly, Strontium and Oxygen isotope analysis suggest that the individual is likely to have originated from outside Britain. This potentially sheds light on the origins of the strain in Britain and its subsequent spread to other parts of the world, including the Americas where the 3I lineage of M. leprae is still found in some southern states of America.