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.

Imported and autochthonous leprosy presenting in Madrid (1989-2015): A case series and review of the literature.

BACKGROUND: Leprosy remains infrequent in non-endemic areas. The objective of this study was to describe the cases of leprosy reviewed at a referral unit for imported diseases in Europe and to compare these findings with published data on imported leprosy. METHODS: Cases of leprosy evaluated at a referral centre are described and salient features of autochthonous and imported cases are compared. A review of the literature on imported leprosy was performed. RESULTS: During the study period, 25 patients with leprosy were followed-up (10 were autochthonous cases and 15 were considered to be imported). Regarding imported cases, the majority were diagnosed in Latin American immigrants (10/15, 67%), mean age was 42 years, there were no differences in gender distribution, estimated average time from arrival in Spain to first visit at the unit was 3 years and from symptom onset to diagnosis was 2 years. Over 80% of imported cases had multibacillary disease and over one third of patients had been previously diagnosed with leprosy. One third had received alternate incorrect diagnoses initially, <50% of patients with imported leprosy completed standard therapy and were considered cured and over one third were lost to follow-up. CONCLUSIONS: Leprosy remains a complex disease for healthcare professionals unfamiliar with this infection. Manifestations are polymorphic so misdiagnoses and consequent delays in diagnosis are not infrequent and may lead to resulting disabilities. Early diagnosis and management are essential to prevent sequelae and possible transmission. Improving access to health care, especially for vulnerable groups, would be necessary to advance in the control of this disease.

The leprosarium of Saint-Thomas d'Aizier: The cementochronological proof of the medieval decline of Hansen disease in Europe?

This study compares the adult survivorship profiles of people interred in the Saint-Thomas d'Aizier leprosarium, estimated by cementochronology, to eight archaeological series in northern France dated from Late Antiquity to the Late Middle Ages, periods of significant visibility for Hansen's disease (leprosy). The goals are to understand the impact of leprosy on various social groups and to explore the cause of leprosy's decline by analyzing male and female fertility. Survival rates differed between medieval leprosy-free sites and the Saint-Thomas d'Aizier leprosarium, although this difference was statistically significant only for the female leprosarium sample. The selective female frailty, a consequence of social exclusion and the collapse of the quality of life, combined with the infertility of lepromatous couples, offer a multi-causal explanation to the end of the expansion and then decline of leprosy in southern and western European countries.

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.

[Present leprosy situation in the world in 2011].

The epidemiological situation of leprosy is reported by the health division of each country to WHO. The reported data is collected by WHO and is immediately run on the Weekly Epidemiological Record. On this latest edition, data from the beginning of 2010 was reported. The Enhanced global strategy for further reducing the disease burden due to leprosy (plan period: 2011-2015) emphasizes reducing grade-2 disabilities among new cases. The burden of leprosy continues to decline globally as a result of sustained efforts carried out by national leprosy programmes along with continued support from both national and international partners. Improving the management of complications through the development of an effective referral service and increased community awareness about the disease will ensure that cases present for diagnosis at an early stage and will help reduce the disease burden further.

Travel and migration associated infectious diseases morbidity in Europe, 2008.

BACKGROUND: Europeans represent the majority of international travellers and clinicians encountering returned patients have an essential role in recognizing, and communicating travel-associated public health risks. METHODS: To investigate the morbidity of travel associated infectious diseases in European travellers, we analysed diagnoses with demographic, clinical and travel-related predictors of disease, in 6957 ill returned travellers who presented in 2008 to EuroTravNet centres with a presumed travel associated condition. RESULTS: Gastro-intestinal (GI) diseases accounted for 33% of illnesses, followed by febrile systemic illnesses (20%), dermatological conditions (12%) and respiratory illnesses (8%). There were 3 deaths recorded; a sepsis caused by Escherichia coli pyelonephritis, a dengue shock syndrome and a Plasmodium falciparum malaria.GI conditions included bacterial acute diarrhea (6.9%), as well as giardiasis and amebasis (2.3%). Among febrile systemic illnesses with identified pathogens, malaria (5.4%) accounted for most cases followed by dengue (1.9%) and others including chikungunya, rickettsial diseases, leptospirosis, brucellosis, Epstein Barr virus infections, tick-borne encephalitis (TBE) and viral hepatitis. Dermatological conditions were dominated by bacterial infections, arthropod bites, cutaneous larva migrans and animal bites requiring rabies post-exposure prophylaxis and also leishmaniasis, myasis, tungiasis and one case of leprosy. Respiratory illness included 112 cases of tuberculosis including cases of multi-drug resistant or extensively drug resistant tuberculosis, 104 cases of influenza like illness, and 5 cases of Legionnaires disease. Sexually transmitted infections (STI) accounted for 0.6% of total diagnoses and included HIV infection and syphilis. A total of 165 cases of potentially vaccine preventable diseases were reported. Purpose of travel and destination specific risk factors was identified for several diagnoses such as Chagas disease in immigrant travellers from South America and P. falciparum malaria in immigrants from sub-Saharan Africa. Travel within Europe was also associated with health risks with distinctive profiles for Eastern and Western Europe. CONCLUSIONS: In 2008, a broad spectrum of travel associated diseases were diagnosed at EuroTravNet core sites. Diagnoses varied according to regions visited by ill travellers. The spectrum of travel associated morbidity also shows that there is a need to dispel the misconception that travel, close to home, in Europe, is without significant health risk.

Testing conditional independence in diagnostic palaeoepidemiology.

Leprosy was a well-known and dreaded disease in the Middle Ages. A substantial fraction of the adult population carried leprosy-related lesions. Previous research analyzed the occurrence and implications of seven such lesions in samples of medieval skeletons. These analyses were carried out under the assumption of conditional independence among lesion scores. The present paper examines this assumption by developing a test based on the odds ratios and applying the test to three rural medieval samples from Europe: Tirup from the 12th-14th century AD in Jutland, Denmark; Refshale from the 12th-14th century AD on the island of Lolland, Denmark; and Lauchheim from AD 460-680 in southern Germany. Signs of nonzero prevalence of leprosy at death were found in all three samples: Tirup, 25.5% (95% CI, 17.2-34.6%); Refshale, 39.1% (95% CI, 25.5-54.7%); and Lauchheim, 16.2% (95% CI, 10.0-22.9%). It is shown that when leprosy is the prime factor creating variation in the lesion scores in and between samples, the assumption of conditional independence cannot be rejected.

On the origin of leprosy.

Leprosy, a chronic human disease with potentially debilitating neurological consequences, results from infection with Mycobacterium leprae. This unculturable pathogen has undergone extensive reductive evolution, with half of its genome now occupied by pseudogenes. Using comparative genomics, we demonstrated that all extant cases of leprosy are attributable to a single clone whose dissemination worldwide can be retraced from analysis of very rare single-nucleotide polymorphisms. The disease seems to have originated in Eastern Africa or the Near East and spread with successive human migrations. Europeans or North Africans introduced leprosy into West Africa and the Americas within the past 500 years.

On the origin of leprosy

Leprosy, a chronic human disease with potentially debilitating neurological consequences, results from infection with Mycobacterium leprae. This unculturable pathogen has undergone extensive reductive evolution, with half of its genome now occupied by pseudogenes. Using comparative genomics, we demonstrated that all extant cases of leprosy are attributable to a single clone whose dissemination worldwide can be retraced from analysis of very rare single-nucleotide polymorphisms. The disease seems to have originated in Eastern Africa or the Near East and spread with successive human migrations. Europeans or North Africans introduced leprosy into West Africa and the Americas within the past 500 years.

[Health service organization during the age of pestilence. 2]. / Excursus sull'organizzazione dell'assistenza in tempi di pestilenza. Seconda parte.

The author presents the history of the places where patients with epidemic pathologies were isolated. Since the study of medicine began, such places have been known as asclepiei, xenodochi, hospices, lazarettos, sanitary cordons, and quarantine stations and they contributed to controlling epidemics in Europe. Important not only in the context in which they were created, these structures expressed the medical culture and point of view of that age. Although very far from discovering the cause of the pathology due to their lack of scientific knowledge, the medical class sometimes knew how to effectively organize the isolation of patients. The history of such structures interweaves with the long history of Christianity and with the emerging nations of Europe and the city-states of the Italian Renaissance. Previously, in classical Greece and Imperial Rome there had also been "homes for the sick" to isolate patients. Today the world is periodically hit by epidemics. In such moments the medical profession uses its research ability and organizational capabilities but also historical memory to reduce epidemic contagion.

[Ecological interactions among Yersinia in their common reservoir, the rodent]. / Interactions écologiques des Yersinia au sein de l'hôte réservoir commun, le rongeur.

Plague, due to Yersinia pestis, is still active in various foci in the Americas, in Africa and Asia, whereas it has been absent from Europe since the end of the 18th century, after having killed the two-thirds of the continent's inhabitants within four centuries. Various hypothesis have been proposed to attempt to explain the spontaneous "eradication" of plague from Europe, including the improvement of hygiene and habitat, changes in the rat population and cross-immunity induced by other infections, such as salmonellosis, leprosy and other yersiniosis. The only Yersinia currently isolated in Europe are the species genetically related to Y. pestis, Y. pseudotuberculosis and Y. enterocolitica, which are less virulent and mostly enteropathogenic. Y. pestis and Y. pseudotuberculosis have a DNA relatedness of 90%, whereas it is of only 60% with Y. enterocolitica. Y. pseudotuberculosis has been used as efficient vaccine against plague. Present world epidemiological data show that Y. enterocolitica is progressively replacing Y. pseudotuberculosis. Experimental infection by Y. enterocolitica, inducing a transitory and spontaneously cured infection in the immunocompetent host, only inducing opportunistic infections in the immunodeficient host, promotes efficient immunity against plague. Thus, it seems likely that the emergence of some variants of Yersinia, less virulent than Y. pestis, but able to induce a long-lasting protective immunity against plague, have contributed to its eradication by a silent enzootic infection among the wild reservoirs of rodents.

The European-American exchange.

The European-American exchange of infectious diseases was responsible for the demographic havoc of the native population in the New World after 1492. Prior to this date medical writers describe the presence in Spain of viral diseases like influenza, parotitis, smallpox, measles, poliomyelitis, and rabies; there were also rickettsiasis, diphtheria, salmonellosis, plague, tubercolosis, leprosy, malaria, scabies and tinea. In America, before European arrivals, there were no records of human viral diseases, though there were records of rickettsiasis, treponematosis--pinta, yaws and syphilis--leihsmaniasis, amibiasis and perhaps leprosy. With the discovery of America in 1492, Columbus's sailors were contaminated by yaws and spread this disease into Europe. In 1493 influenza, as a zoonosis, was introduced into Santo Domingo and was responsible for the annihilation of the natives of the Antilles in less than a quarter of a century; in 1518 smallpox was also introduced in Santo Domingo and then to the American continent by negro slaves: by the same means measles were introduced in 1531. The previous existence or introduction of other infectious diseases in America is also discussed.