Ancient genomes reveal structural shifts after the arrival of Steppe-related ancestry in the Italian Peninsula.

Across Europe, the genetics of the Chalcolithic/Bronze Age transition is increasingly characterized in terms of an influx of Steppe-related ancestry. The effect of this major shift on the genetic structure of populations in the Italian Peninsula remains underexplored. Here, genome-wide shotgun data for 22 individuals from commingled cave and single burials in Northeastern and Central Italy dated between 3200 and 1500 BCE provide the first genomic characterization of Bronze Age individuals (n = 8; 0.001-1.2× coverage) from the central Italian Peninsula, filling a gap in the literature between 1950 and 1500 BCE. Our study confirms a diversity of ancestry components during the Chalcolithic and the arrival of Steppe-related ancestry in the central Italian Peninsula as early as 1600 BCE, with this ancestry component increasing through time. We detect close patrilineal kinship in the burial patterns of Chalcolithic commingled cave burials and a shift away from this in the Bronze Age (2200-900 BCE) along with lowered runs of homozygosity, which may reflect larger changes in population structure. Finally, we find no evidence that the arrival of Steppe-related ancestry in Central Italy directly led to changes in frequency of 115 phenotypes present in the dataset, rather that the post-Roman Imperial period had a stronger influence, particularly on the frequency of variants associated with protection against Hansen's disease (leprosy). Our study provides a closer look at local dynamics of demography and phenotypic shifts as they occurred as part of a broader phenomenon of widespread admixture during the Chalcolithic/Bronze Age transition.

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.

The arms race between man and Mycobacterium tuberculosis: Time to regroup.

An arms race is an appropriate metaphor to use for the interaction of man and Mycobacterium tuberculosis (M.tb) through the millennia. Estimates of the time of infection of modern humans with M.tb often pre-date the Out-of-Africa migration. Humans have adapted to the changing environment during the migration with respect to climate, food sources and encounters with local pathogens. More recently, there has been adaptation to the demographic changes brought about in the majority of the human population by the Neolithic revolution. By chance and/or selection, specific variants in immune defence have arisen in different population groups. These select for M.tb strains more fit to cause disease and be transmitted, sometimes by exploiting defence systems effective on other bacteria. The different selection pressures on the M.tb lineages carried by specific human groups have resulted in a worldwide M.tb population that is geographically structured according to the humans historically found there. A similar structure is seen with pathogens such as M. leprae and Helicobacter pylori. Modern M.tb strains have emerged which may be more fit, such as the Beijing lineage, leading to their rapid spread both in the areas where they arose, and into new areas after recent introduction. The speed at which this is occurring is outpacing coevolution for the time being. By using the results of genome wide and other association studies, as well as admixture mapping and 'natural experiments' in areas where both a number of populations, admixed populations, and a variety of M.tb strains occur, we can investigate the forces that have driven the coevolution of man and M.tb. The diversity of human and bacterial genetic background may be used in the future to discover and target the specific host-pathogen interactions leading to tuberculosis diseases, which suggests the potential for rational design of vaccines and host-directed therapies.

Unsolved matters in leprosy: a descriptive review and call for further research.

Leprosy, a chronic mycobacterial infection caused by Mycobacterium leprae, is an infectious disease that has ravaged human societies throughout millennia. This ancestral pathogen causes disfiguring cutaneous lesions, peripheral nerve injury, ostearticular deformity, limb loss and dysfunction, blindness and stigma. Despite ongoing efforts in interrupting leprosy transmission, large numbers of new cases are persistently identified in many endemic areas. Moreover, at the time of diagnosis, most newly identified cases have considerable neurologic disability. Many challenges remain in our understanding of the epidemiology of leprosy including: (a) the precise mode and route of transmission; (b) the socioeconomic, environmental, and behavioral factors that promote its transmission; and

A migration-driven model for the historical spread of leprosy in medieval Eastern and Central Europe.

Leprosy was rare in Europe during the Roman period, yet its prevalence increased dramatically in medieval times. We examined human remains, with paleopathological lesions indicative of leprosy, dated to the 6th-11th century AD, from Central and Eastern Europe and Byzantine Anatolia. Analysis of ancient DNA and bacterial cell wall lipid biomarkers revealed Mycobacterium leprae in skeletal remains from 6th-8th century Northern Italy, 7th-11th century Hungary, 8th-9th century Austria, the Slavic Greater Moravian Empire of the 9th-10th century and 8th-10th century Byzantine samples from Northern Anatolia. These data were analyzed alongside findings published by others. M. leprae is an obligate human pathogen that has undergone an evolutionary bottleneck followed by clonal expansion. Therefore M. leprae genotypes and sub-genotypes give information about the human populations they have infected and their migration. Although data are limited, genotyping demonstrates that historical M. leprae from Byzantine Anatolia, Eastern and Central Europe resembles modern strains in Asia Minor rather than the recently characterized historical strains from North West Europe. The westward migration of peoples from Central Asia in the first millennium may have introduced different M. leprae strains into medieval Europe and certainly would have facilitated the spread of any existing leprosy. The subsequent decline of M. leprae in Europe may be due to increased host resistance. However, molecular evidence of historical leprosy and tuberculosis co-infections suggests that death from tuberculosis in leprosy patients was also a factor.

Human migration, railways and the geographic distribution of leprosy in Rio Grande do Norte State--Brazil.

INTRODUCTION: Leprosy is a public health problem in Brazil where 31,044 new cases were detected in 2013. Rio Grande do Norte is a small Brazilian state with a rate of leprosy lower than other areas in the same region, for unknown reasons. OBJECTIVES: We present here a review based on the analysis of a database of registered leprosy cases in Rio Grande do Norte state, comparing leprosy's geographic distribution among municipalities with local socio-economic and public health indicators and with historical documents about human migration in this Brazilian region. RESULTS: The current distribution of leprosy in Rio Grande do Norte did not show correlation with socio-economic or public health indicators at the municipal level, but it appears related to economically emerging municipalities 100 years ago, with spread facilitated by railroads and train stations. Drought-related migratory movements which occurred from this state to leprosy endemic areas within the same period may be involved in the introduction of leprosy and with its present distribution within Rio Grande do Norte. CONCLUSIONS: Leprosy may disseminate slowly, over many decades in certain circumstances, such as in small cities with few cases. This is a very unusual situation currently and a unique opportunity for epidemiologic studies of leprosy as an emerging disease.

Identification of urban leprosy clusters.

Overpopulation of urban areas results from constant migrations that cause disordered urban growth, constituting clusters defined as sets of people or activities concentrated in relatively small physical spaces that often involve precarious conditions. Aim. Using residential grouping, the aim was to identify possible clusters of individuals in São José do Rio Preto, Sao Paulo, Brazil, who have or have had leprosy. Methods. A population-based, descriptive, ecological study using the MapInfo and CrimeStat techniques, geoprocessing, and space-time analysis evaluated the location of 425 people treated for leprosy between 1998 and 2010. Clusters were defined as concentrations of at least 8 people with leprosy; a distance of up to 300 meters between residences was adopted. Additionally, the year of starting treatment and the clinical forms of the disease were analyzed. Results. Ninety-eight (23.1%) of 425 geocoded cases were located within one of ten clusters identified in this study, and 129 cases (30.3%) were in the region of a second-order cluster, an area considered of high risk for the disease. Conclusion. This study identified ten clusters of leprosy cases in the city and identified an area of high risk for the appearance of new cases of the disease.

Identification of urban leprosy clusters

Overpopulation of urban areas results from constant migrations that cause disordered urban growth, constituting clusters defined as sets of people or activities concentrated in relatively small physical spaces that often involve precarious conditions. Aim. Using residential grouping, the aim was to identify possible clusters of individuals in São José do Rio Preto, Sao Paulo, Brazil, who have or have had leprosy. METHODS: A population-based, descriptive, ecological study using the MapInfo and CrimeStat techniques, geoprocessing, and space-time analysis evaluated the location of 425 people treated for leprosy between 1998 and 2010. Clusters were defined as concentrations of at least 8 people with leprosy; a distance of up to 300 meters between residences was adopted. Additionally, the year of starting treatment and the clinical forms of the disease were analyzed. RESULTS: Ninety-eight (23.1%) of 425 geocoded cases were located within one of ten clusters identified in this study, and 129 cases (30.3%) were in the region of a second-order cluster, an area considered of high risk for the disease. CONCLUSION: This study identified ten clusters of leprosy cases in the city and identified an area of high risk for the appearance of new cases of the disease.

[Leprosy diagnosis in municipalities other than the patients' place of residence: spatial analysis, 2001-2009]. / Diagnóstico da hanseníase fora do município de residência: uma abordagem espacial, 2001 a 2009.

The study analyzed the flow of persons with leprosy from their municipality (county) of residence to that of their diagnosis in a highly endemic area in Brazil. The study was based on data from the National Information System for Notifiable Diseases from 2001 to 2009 in the States of Maranhão, Pará, Tocantins, and Piauí. Of the 373 municipalities, 349 (93.6%) had at least one resident with leprosy that had been diagnosed in a different municipality (4,325 cases, or 5.2% of the total). The municipalities with the most cases reported elsewhere were Timon (248) and São José de Ribamar (201), Maranhão State. The municipalities that received the most exogenous cases for diagnosis were São Luís (719), capital of Maranhão, and Teresina (516), capital of Piauí. Goiânia (146), capital of Goiás, and the Federal District (42) also reported numerous cases, even though they are located more than 1,000 km from the endemic area. The flow indicates gaps in the decentralization of comprehensive care for persons with leprosy and calls attention to the difficulties associated with patient monitoring during and after multidrug therapy.

Diagnóstico da hanseníase fora do município de residência: uma abordagem espacial, 2001 a 2009 / Leprosy diagnosis in municipalities other than the patients' place of residence: spatial analysis, 2001-2009

Caracterizar o fluxo de pessoas afetadas pela hanseníase, do município de residência para o de diagnóstico, em área de alta endemicidade no Brasil. Estudo baseado em dados do Sistema de Informação de Agravos e Notificação de 2001-2009, nos estados do Maranhão, Pará, Tocantins e Piauí. Dos 373 municípios, 349 (93,6%) tiveram pelo menos um residente afetado pela hanseníase notificado em outro município (4.325 casos, 5,2% dos notificados). Os municípios com maior número de casos notificados fora de sua residência foram Timon (248) e São José de Ribamar (201), no Maranhão. Os municípios que mais receberam casos para diagnóstico foram São Luís (719) e Teresina (516). Destacam-se Goiânia (146) e o Distrito Federal (42) como polos de notificações de casos residentes no agregado, mesmo a mais de 1.000km de distância da área. O fluxo observado indica lacunas na descentralização do processo de atenção integral à pessoa afetada pela hanseníase e chama atenção para as dificuldades e desafios associados com o acompanhamento durante e após a poliquimioterapia.

The study analyzed the flow of persons with leprosy from their municipality (county) of residence to that of their diagnosis in a highly endemic area in Brazil. The study was based on data from the National Information System for Notifiable Diseases from 2001 to 2009 in the States of Maranhão, Pará, Tocantins, and Piauí. Of the 373 municipalities, 349 (93.6%) had at least one resident with leprosy that had been diagnosed in a different municipality (4,325 cases, or 5.2% of the total). The municipalities with the most cases reported elsewhere were Timon (248) and São José de Ribamar (201), Maranhão State. The municipalities that received the most exogenous cases for diagnosis were São Luís (719), capital of Maranhão, and Teresina (516), capital of Piauí. Goiânia (146), capital of Goiás, and the Federal District (42) also reported numerous cases, even though they are located more than 1,000km from the endemic area. The flow indicates gaps in the decentralization of comprehensive care for persons with leprosy and calls attention to the difficulties associated with patient monitoring during and after multidrug therapy.

Lepra importada y su dificultad en el medio actual: a propósito de 7 casos / The Current Challenge of Imported Leprosy in Spain: A Study of 7 Cases

Introducción: aunque los focos históricos de infección leprosa en nuestro país están controlados y son prácticamente inactivos, aún se siguen diagnosticando algunos casos autóctonos aislados. La elevada movilidad poblacional actual ha traído consigo un aumento en la incidencia de casos importados de países endémicos, lo que está motivando un cambio en las características epidemiológicas del paciente afecto de lepra. Objetivos: el propósito de este artículo es poner de manifiesto las características clínicas, epidemiológicas, dermatopatológicas, microbiológicas y terapéuticas de los pacientes diagnosticados de lepra en los últimos 5 años en nuestro Servicio. Material y método: presentamos los casos de lepra importada que hemos valorado en nuestro Servicio desde el año 2004 al 2009.Resultadosse trata de 7 casos de lepra, 3 varones y 4 mujeres, de edades comprendidas entre los 26 y los 80 años, 2 de tipo tuberculoide, 2 borderline tuberculoide y 3 de tipo indeterminada. Todos procedían de países sudamericanos o sudafricanos donde adquirieron la enfermedad, aunque residían en España en ese momento. Sólo uno de los pacientes era natural de Málaga, pero trabajó como misionero en Venezuela durante 25 años. En ningún caso se logró demostrar la existencia de bacilos mediante la técnica de Ziehl-Neelsen, siendo la baciloscopia igualmente negativa. Conclusiones: queremos destacar los cambios epidemiológicos que hemos observado en los casos de lepra diagnosticados en nuestro Servicio, la mayoría de los cuales son importados. Es importante seguir manteniendo la sospecha clínica de lepra ante dermatitis granulomatosas, especialmente en pacientes de países endémicos (AU)

Background: although the foci of leprosy once present in Spain are now under control and almost inactive, isolated cases are still occasionally diagnosed. Meanwhile, population migration has brought about an increase in the incidence of cases corresponding to individuals from countries where leprosy is endemic, leading to changes in the epidemiology of this disease. Objectives: the aim of this paper was to describe the clinical, epidemiologic, dermatologic, microbiologic, and therapeutic characteristics of cases of leprosy in our department in the last 5 years. Material and methods: we report the cases of imported leprosy seen in our department between 2004 and 2009. Results: seven patients with leprosy (3 men and 4 women; age range, 26-80 years) were diagnosed; 2 were cases of tuberculoid leprosy, 2 borderline tuberculoid leprosy, and 3 indeterminate. All patients acquired the disease in South American or South African countries, but were residing in Spain at the time of diagnosis. One patient was a Spaniard, from Malaga, who had worked as a missionary in Venezuela for 25 years. The presence of the bacterium by either Ziehl-Neelsen stain or bacilloscopy could not be demonstrated in any of the patients. Conclusions: we would like to draw attention to the changes we have observed in the characteristics of cases of leprosy seen in our department, the majority of which are imported. It is important to maintain a clinical suspicion of leprosy in cases of granulomatous dermatitis, particularly in patients from countries where the disease is endemic (AU)

Dos casos de lepra en Valladolid / Two cases of leprosy in Valladolid

La lepra continúa siendo un importante problema de salud en todo el mundo y aunque en nuestro continente no alcanza cifras de endemia, parece existir una tendencia al alza debido al número de casos importados diagnosticados cada año. Se describen 2 casos de lepra lepromatosa diagnosticados en Valladolid en un periodo de 5 meses. El último caso declarado de esta enfermedad en nuestra comunidad data de hace más de 20 años

Leprosy is still a major health problem on a worldwide level, and although it does not reach endemic levels on our continent, it seems that there is an upward trend due to the number of imported cases diagnosed each year. We present two cases of lepromatous leprosy diagnosed in Valladolid within a five-month period. The last reported case of this disease in our community was over 20 years ago

Hanseniase e migracao no municipio de Maringa - Parana: 1957-1997 / ?

Este trabalho e um estudo historico-descritivo de natureza qualitativa, cujo o objetivo e estabelecer a relacao entre doenca e o movimento migratorio da hanseniase no municipio de Maringa. Foram entrevistadas 11 pessoas entre portadores e ex-portadores da doenca e profissionais de saude que compartilharam do mesmo problema de forma singular, e vivenciaram a doenca no periodo de 1957-1997. As historias de vida relatadas foram analisadas segundo os seguintes aspectos da hanseniase: os servicos de saude oferecidos, as duas faces da doenca, tratamento, e hanseniase e migracao. Atraves deste estudo, percebemos que um dos motivos da vinda de hansenianos para a regiao foi a tentativa de manter a uniao de sua familia, no que iam de encontro a politica de controle da epoca, do isolamento compulsorio.