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.

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.

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.

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.

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.

Mycobacterium leprae genomes from a British medieval leprosy hospital: towards understanding an ancient epidemic.

BACKGROUND: Leprosy has afflicted humankind throughout history leaving evidence in both early texts and the archaeological record. In Britain, leprosy was widespread throughout the Middle Ages until its gradual and unexplained decline between the 14th and 16th centuries. The nature of this ancient endemic leprosy and its relationship to modern strains is only partly understood. Modern leprosy strains are currently divided into 5 phylogenetic groups, types 0 to 4, each with strong geographical links. Until recently, European strains, both ancient and modern, were thought to be exclusively type 3 strains. However, evidence for type 2 strains, a group normally associated with Central Asia and the Middle East, has recently been found in archaeological samples in Scandinavia and from two skeletons from the medieval leprosy hospital (or leprosarium) of St Mary Magdalen, near Winchester, England. RESULTS: Here we report the genotypic analysis and whole genome sequencing of two further ancient M. leprae genomes extracted from the remains of two individuals, Sk14 and Sk27, that were excavated from 10th-12th century burials at the leprosarium of St Mary Magdalen. DNA was extracted from the surfaces of bones showing osteological signs of leprosy. Known M. leprae polymorphisms were PCR amplified and Sanger sequenced, while draft genomes were generated by enriching for M. leprae DNA, and Illumina sequencing. SNP-typing and phylogenetic analysis of the draft genomes placed both of these ancient strains in the conserved type 2 group, with very few novel SNPs compared to other ancient or modern strains. CONCLUSIONS: The genomes of the two newly sequenced M. leprae strains group firmly with other type 2F strains. Moreover, the M. leprae strain most closely related to one of the strains, Sk14, in the worldwide phylogeny is a contemporaneous ancient St Magdalen skeleton, vividly illustrating the epidemic and clonal nature of leprosy at this site. The prevalence of these type 2 strains indicates that type 2F strains, in contrast to later European and associated North American type 3 isolates, may have been the co-dominant or even the predominant genotype at this location during the 11th century.

The prevalence of ocular complications in leprosy patients seen in the United Kingdom over a period of 21 years.

OBJECTIVE: The objective of this study was to determine the prevalence of ocular complications and blindness among leprosy patients presenting in the United Kingdom. METHODS: Observational prospective study. RESULTS: A total of 126 consecutive leprosy patients attending their ophthalmic visit were examined, out of which 18 patients were blind in one eye (14.3%) and five patients were blind in both the eyes (4.0%). Visual acuity of ≥ 6/18 was present in 96 patients (76.2%). A total of 65 patients (51.6%) had an ocular complication and 28 patients (22.2%) had a sight-threatening leprosy complication (lagophthalmos, severe corneal, or iris disease). The most common ocular complications were impaired lid closure (24 patients, 19%), impaired corneal sensation (20 patients, 15.9%), cataract (20 patients, 15.9%), mild corneal opacity (17 patients, 13.5%), and iris atrophy (17 patients, 13.5%). Impaired corneal sensation was associated with vision <6/18 (P<0.001, OR 13.5, 95% CI 5.14-35.44) and vision <3/60 (P=0.01 OR 6.42, 95% CI 2.15-19.15). Impaired lid closure was significantly associated with increasing age (P=0.029, OR 1.039, 95% CI 1.0-1.08) and vision <3/60 (P=0.03, OR 6.06, 95% CI 1.81-20.24). CONCLUSION: There is a significant rate of ocular complications and blindness seen in leprosy patients in the United Kingdom, and over one in five had a potentially sight-threatening ocular complication. Health professionals and all leprosy patients, including those cured of the disease, need to be aware that new eye symptoms and signs require prompt ophthalmology review to prevent avoidable blindness, due to the life-long risk of sight-threatening ocular complications.

The pathology of HIV infection.

The acquired immunodeficiency syndrome (AIDS) is the result of a human immunodeficiency virus (HIV) infection damaging the cell-mediated immune system. A wide range of opportunistic infections (OI) and tumours develop; additionally, HIV directly damages some organs. The patterns of opportunistic diseases (OD) are different in different parts of the world, depending on the local prevalence of latent and acquired infections and on the survival of HIV-infected patients. OD patterns change as people migrate. Recently introduced highly active anti-retroviral chemotherapy prevents many of the common OIs, but also introduces a new range of toxic pathological damage. Longer survival permits development of new HIV-related diseases. The pathology of HIV/AIDS is not static but changing.