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1.
Emerg Microbes Infect ; 8(1): 1479-1489, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31621517

RESUMEN

Reports on antimicrobial resistance (AMR) of Mycobacterium leprae, relationship with bacteriological index (BI), and transmission in China are limited. We investigated the emergence of AMR mutations, the relationship between BI and AMR in complete, moderate and lack of BI decline cases, and molecular epidemiological features of AMR cases by enrolling 290 leprosy cases from four endemic provinces. Seven (2.41%), one (0.34%), five (1.72%), one (0.34%), and one (0.34%) strains had single mutations in folP1, rpoC, gyrA, gyrB, and 23S rRNA, respectively. Double mutations in folP1 and gyrA, rpoB and gyrA, and gyrA and 23S rRNA were observed in one (0.34%) strain each. Mutated strains occurred in three out of 81 (95% CI-0.005-0.079, p = 0.083) cases with complete BI decline, in seven out of 103 (95% CI 0.018-0.117, p = 0.008) cases with moderate BI decline, and in four out of 34 (95% CI 0.003-0.231, p = 0.044) cases with lack of BI decline. Most of these mutated strains were geographically separated and diverged genotypically. AMR mutations may not be the main cause of the lack of BI decline. The low transmission of AMR strains at the county level indicates an ongoing transmission at close contact levels.


Asunto(s)
Farmacorresistencia Bacteriana , Leprostáticos/farmacología , Lepra/microbiología , Mycobacterium leprae/efectos de los fármacos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , China/epidemiología , Femenino , Humanos , Lepra/epidemiología , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Mutación , Mycobacterium leprae/clasificación , Mycobacterium leprae/genética , Mycobacterium leprae/aislamiento & purificación , Filogenia , Adulto Joven
3.
Emerg Infect Dis ; 24(8): 1584-1585, 2018 08.
Artículo en Inglés | MEDLINE | ID: mdl-30016255

RESUMEN

Skin biopsies from US leprosy patients were tested for mutations associated with drug resistance. Dapsone resistance was found in 4 of 6 biopsies from American Samoa patients. No resistance was observed in patients from other origins. The high rate of dapsone resistance in patients from American Samoa warrants further investigation.


Asunto(s)
Dapsona/uso terapéutico , Farmacorresistencia Bacteriana/genética , Genes Bacterianos , Leprostáticos/uso terapéutico , Lepra/tratamiento farmacológico , Mycobacterium leprae/efectos de los fármacos , Mycobacterium leprae/genética , Samoa Americana , Biopsia , Clofazimina/uso terapéutico , Esquema de Medicación , Humanos , Lepra/diagnóstico , Lepra/microbiología , Pruebas de Sensibilidad Microbiana , Mutación , Mycobacterium leprae/clasificación , Mycobacterium leprae/aislamiento & purificación , Rifampin/uso terapéutico , Piel/efectos de los fármacos , Piel/microbiología
4.
PLoS Pathog ; 14(5): e1006997, 2018 05.
Artículo en Inglés | MEDLINE | ID: mdl-29746563

RESUMEN

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.


Asunto(s)
Lepra/historia , Mycobacterium leprae/genética , ADN Bacteriano/genética , ADN Bacteriano/historia , Europa (Continente)/epidemiología , Evolución Molecular , Variación Genética , Genoma Bacteriano , Historia Medieval , Interacciones Huésped-Patógeno/genética , Humanos , Lepra/epidemiología , Lepra/microbiología , Mycobacterium leprae/clasificación , Mycobacterium leprae/patogenicidad , Filogenia , Filogeografía , Polimorfismo de Nucleótido Simple
5.
Infect Genet Evol ; 62: 20-26, 2018 08.
Artículo en Inglés | MEDLINE | ID: mdl-29665434

RESUMEN

Leprosy (Hansen's Disease) has occurred throughout human history, and persists today at a low prevalence in most populations. Caused by Mycobacterium leprae, the infection primarily involves the skin, mucosa and peripheral nerves. The susceptible host range for Mycobacterium leprae is quite narrow. Besides humans, nine banded armadillos (Dasypus novemcinctus) and red squirrels (Sciurus vulgaris) are the only other natural hosts for M. leprae, but only armadillos recapitulate the disease as seen in humans. Armadillos across the Southern United States harbor a single predominant genotypic strain (SNP Type-3I) of M. leprae, which is also implicated in the zoonotic transmission of leprosy. We investigated, whether the zoonotic strain (3I) has any notable growth advantages in armadillos over another genetically distant strain-type (SNP Type-4P) of M. leprae, and if M. leprae strains manifest any notably different pathology among armadillos. We co-infected armadillos (n = 6) with 2 × 109 highly viable M. leprae of both strains and assessed the relative growth and dissemination of each strain in the animals. We also analyzed 12 additional armadillos, 6 each individually infected with the same quantity of either strain. The infections were allowed to fulminate and the clinical manifestations of the disease were noted. Animals were humanely sacrificed at the terminal stage of infection and the number of bacilli per gram of liver, spleen and lymph node tissue were enumerated by Q-PCR assay. The growth of M. leprae strain 4P was significantly higher (P < 0.05) than 3I when each strain was propagated individually in armadillos. Significantly (P < 0.0001) higher growth of the 4P strain also was confirmed among animals co-infected with both 3I and 4P strain types using whole genome sequencing. Interestingly, the zoonotic strain does not exhibit any growth advantage in these non-human hosts, but the varied proliferation of the two M. leprae strains within armadillos suggest there are notable pathological variations between M. leprae strain-types.


Asunto(s)
Armadillos/microbiología , Genotipo , Lepra/veterinaria , Mycobacterium leprae/crecimiento & desarrollo , Mycobacterium leprae/genética , Polimorfismo de Nucleótido Simple , Américas/epidemiología , Animales , Animales Salvajes , Variación Genética , Lepra/epidemiología , Lepra/microbiología , Ratones , Mycobacterium leprae/clasificación , Zoonosis
6.
Pathog Glob Health ; 112(2): 79-85, 2018 03.
Artículo en Inglés | MEDLINE | ID: mdl-29405082

RESUMEN

This study analyzed the genetic diversity by MIRU-VNTR of Mycobacterium leprae isolates from nasal cavities and related to epidemiological and clinical data. The sample consisted of 48 newly diagnosed leprosy cases that tested positive for M. leprae PCR in nasal secretion (NS) attending to the National Reference Center of Dermatology Dona Libania (CDERM), Fortaleza, Brazil. Total DNA was extracted from NS of each patient and used for amplification of four M. leprae VNTR loci. Four clusters of M. leprae isolates were formed with identical genotypes. In the spatial analysis, 12 leprosy cases presented similar genotypes organized into 4 clusters. The most common genotypes in the current study was AC8b: 8, AC9: 7, AC8a: 8, GTA9: 10, which may represent a genotype of circulating strains most often in Ceará. A minimum set of four MIRU-VNTR loci was demonstrated to study the genetic diversity of M. leprae isolates from NS.


Asunto(s)
Variación Genética , Genotipo , Técnicas de Genotipaje/métodos , Lepra/microbiología , Repeticiones de Minisatélite , Mycobacterium leprae/clasificación , Cavidad Nasal/microbiología , Adolescente , Adulto , Anciano , Líquidos Corporales/microbiología , Brasil , Niño , Análisis por Conglomerados , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mycobacterium leprae/genética , Mycobacterium leprae/aislamiento & purificación , Adulto Joven
7.
PLoS Negl Trop Dis ; 12(1): e0006190, 2018 01.
Artículo en Inglés | MEDLINE | ID: mdl-29381722

RESUMEN

Leprosy is caused by the bacterial pathogens Mycobacterium leprae and Mycobacterium lepromatosis. Apart from humans, animals such as nine-banded armadillos in the Americas and red squirrels in the British Isles are naturally infected with M. leprae. Natural leprosy has also been reported in certain nonhuman primates, but it is not known whether these occurrences are due to incidental infections by human M. leprae strains or by M. leprae strains specific to nonhuman primates. In this study, complete M. leprae genomes from three naturally infected nonhuman primates (a chimpanzee from Sierra Leone, a sooty mangabey from West Africa, and a cynomolgus macaque from The Philippines) were sequenced. Phylogenetic analyses showed that the cynomolgus macaque M. leprae strain is most closely related to a human M. leprae strain from New Caledonia, whereas the chimpanzee and sooty mangabey M. leprae strains belong to a human M. leprae lineage commonly found in West Africa. Additionally, samples from ring-tailed lemurs from the Bezà Mahafaly Special Reserve, Madagascar, and chimpanzees from Ngogo, Kibale National Park, Uganda, were screened using quantitative PCR assays, to assess the prevalence of M. leprae in wild nonhuman primates. However, these samples did not show evidence of M. leprae infection. Overall, this study adds genomic data for nonhuman primate M. leprae strains to the existing M. leprae literature and finds that this pathogen can be transmitted from humans to nonhuman primates as well as between nonhuman primate species. While the prevalence of natural leprosy in nonhuman primates is likely low, nevertheless, future studies should continue to explore the prevalence of leprosy-causing pathogens in the wild.


Asunto(s)
Genoma Bacteriano , Lepra/veterinaria , Mycobacterium leprae/genética , Mycobacterium leprae/aislamiento & purificación , Enfermedades de los Primates/microbiología , África Occidental , Animales , Cercocebus atys , Variación Genética , Lemur , Lepra/microbiología , Macaca fascicularis , Mycobacterium leprae/clasificación , Pan troglodytes , Filipinas , Filogenia
8.
J Glob Antimicrob Resist ; 12: 214-219, 2018 03.
Artículo en Inglés | MEDLINE | ID: mdl-29097343

RESUMEN

OBJECTIVES: The emergence of multidrug-resistant (MDR) organisms for any infectious disease is a public health concern. Global efforts to control leprosy by intensive chemotherapy have led to a significant decrease in the number of registered patients. Currently recommended control measures for treating leprosy with multidrug therapy (MDT) were designed to prevent the spread of dapsone-resistant Mycobacterium leprae strains. Here we report the identification of MDR M. leprae from relapse leprosy patients from endemic regions in India. METHODS: Resistance profiles to rifampicin, dapsone and ofloxacin of the isolated strains were confirmed by identification of mutations in genes previously shown to be associated with resistance to each drug. Between 2009-2016, slit-skin smear samples were collected from 239 relapse and 11 new leprosy cases from hospitals of The Leprosy Mission across India. DNA was extracted from the samples and was analysed by PCR targeting the rpoB, folP and gyrA genes associated with resistance to rifampicin, dapsone and ofloxacin, respectively, in M. leprae. M. leprae Thai-53 (wild-type) and Zensho-4 (MDR) were used as reference strains. RESULTS: Fifteen strains showed representative mutations in at least two resistance genes. Two strains showed mutations in all three genes responsible for drug resistance. Seven, seven and one strain, respectively, showed mutations in genes responsible for rifampicin and dapsone resistance, for dapsone and ofloxacin resistance and for rifampicin and ofloxacin resistance. CONCLUSION: This study showed the emergence of MDR M. leprae in MDT-treated leprosy patients from endemic regions of India.


Asunto(s)
Farmacorresistencia Bacteriana , Leprostáticos/farmacología , Lepra/microbiología , Mycobacterium leprae/efectos de los fármacos , Mycobacterium leprae/genética , Adolescente , Adulto , Anciano , Femenino , Humanos , India , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Mycobacterium leprae/clasificación , Mycobacterium leprae/aislamiento & purificación , Adulto Joven
9.
J Med Microbiol ; 66(11): 1640-1649, 2017 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-28984227

RESUMEN

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.


Asunto(s)
Lepra Lepromatosa/epidemiología , Mycobacterium leprae/genética , Mycobacterium leprae/aislamiento & purificación , Adulto , Femenino , Genotipo , Historia Medieval , Humanos , Lepra Lepromatosa/diagnóstico , Lepra Lepromatosa/historia , Lepra Lepromatosa/microbiología , Mycobacterium leprae/clasificación , Osteología , Cráneo/microbiología , Reino Unido
10.
PLoS Negl Trop Dis ; 11(6): e0005598, 2017 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-28617800

RESUMEN

BACKGROUND: Since leprosy is both treated and controlled by multidrug therapy (MDT) it is important to monitor recurrent cases for drug resistance and to distinguish between relapse and reinfection as a means of assessing therapeutic efficacy. All three objectives can be reached with single nucleotide resolution using next generation sequencing and bioinformatics analysis of Mycobacterium leprae DNA present in human skin. METHODOLOGY: DNA was isolated by means of optimized extraction and enrichment methods from samples from three recurrent cases in leprosy patients participating in an open-label, randomized, controlled clinical trial of uniform MDT in Brazil (U-MDT/CT-BR). Genome-wide sequencing of M. leprae was performed and the resultant sequence assemblies analyzed in silico. PRINCIPAL FINDINGS: In all three cases, no mutations responsible for resistance to rifampicin, dapsone and ofloxacin were found, thus eliminating drug resistance as a possible cause of disease recurrence. However, sequence differences were detected between the strains from the first and second disease episodes in all three patients. In one case, clear evidence was obtained for reinfection with an unrelated strain whereas in the other two cases, relapse appeared more probable. CONCLUSIONS/SIGNIFICANCE: This is the first report of using M. leprae whole genome sequencing to reveal that treated and cured leprosy patients who remain in endemic areas can be reinfected by another strain. Next generation sequencing can be applied reliably to M. leprae DNA extracted from biopsies to discriminate between cases of relapse and reinfection, thereby providing a powerful tool for evaluating different outcomes of therapeutic regimens and for following disease transmission.


Asunto(s)
Genoma Bacteriano , Lepra/diagnóstico , Tipificación Molecular/métodos , Mycobacterium leprae/clasificación , Mycobacterium leprae/genética , Análisis de Secuencia de ADN/métodos , Adolescente , Adulto , Brasil , Biología Computacional/métodos , ADN Bacteriano/aislamiento & purificación , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Humanos , Masculino , Mycobacterium leprae/aislamiento & purificación , Ensayos Clínicos Controlados Aleatorios como Asunto , Recurrencia , Adulto Joven
12.
Science ; 354(6313): 744-747, 2016 11 11.
Artículo en Inglés | MEDLINE | ID: mdl-27846605

RESUMEN

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.


Asunto(s)
Reservorios de Enfermedades/microbiología , Lepra/microbiología , Lepra/transmisión , Mycobacterium/aislamiento & purificación , Sciuridae/microbiología , Animales , Genómica , Humanos , Lepra/epidemiología , Lepra/genética , México/epidemiología , Mycobacterium/clasificación , Mycobacterium/genética , Mycobacterium leprae/clasificación , Mycobacterium leprae/genética , Filogenia , Polimorfismo Genético , Dominios Proteicos , Receptor Toll-Like 1/química , Receptor Toll-Like 1/genética , Reino Unido/epidemiología
14.
Indian J Med Microbiol ; 34(3): 315-21, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27514953

RESUMEN

PURPOSE: Leprosy is a chronic systemic infectious disease caused by Mycobacterium leprae, one of the first organisms to be established as the cause for disease in humans. Because of high prevalence pockets of leprosy in the endemic regions, it is necessary to identify the possible sources of M. leprae in the environment and its mode of transmission. MATERIALS AND METHODS: Slit skin smears (SSSs) from lesions were collected in 70% ethanol from 50 leprosy cases staying in the leprosy resettlement village and hospital from a high endemic area. One hundred and sixty soil samples were collected from different areas around the leprosy hospital and from the resettlement village of cured leprosy patients where active cases also resided at the time of sample collection. M. leprae specific gene region (RLEP 129 bp) and 16S rRNA targets were used for polymerase chain reaction (PCR) based detection for the presence and viability of M. leprae. An rpoT region was also amplified to determine presence of numbers of 6 bp tandem repeats. RESULTS: All the SSS samples collected from patients showed three copies of rpoT region (6 bp tandem repeat, an ancient Indian type). Fifty-two soil samples showed presence of M. leprae DNA whereas M. leprae specific 16S rRNA gene was amplified in sixteen of these samples. PCR amplification and fragment length analysis showed 91 bp, i.e., three copies of the rpoT 6 bp tandem repeats from soil samples and similar three copies observed in patient samples. CONCLUSION: Presence of viable M. leprae in the soil having same rpoT genotype of M. leprae noted in patients suggests that it could be the same strain of M. leprae. M. leprae found in the soil could be the one that is excreted out by the patient. Significance of its viability in the environment and its pathogenicity with respect to transmission needs to be further explored. Findings of this study might provide possible insights for further exploration into understanding transmission patterns in leprosy and also will throw light on identifying potential for existence of extra human source or reservoirs of M. leprae, if any.


Asunto(s)
Lepra/microbiología , Mycobacterium leprae/aislamiento & purificación , Microbiología del Suelo , Proteínas Bacterianas/genética , ADN Bacteriano/química , ADN Bacteriano/genética , ADN Ribosómico/genética , Genotipo , Humanos , Mycobacterium leprae/clasificación , Mycobacterium leprae/genética , Reacción en Cadena de la Polimerasa , ARN Ribosómico 16S/genética , Factor sigma/genética
15.
Lepr Rev ; 87(4): 486-500, 2016 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-30226353

RESUMEN

Background: This study compares the strains of genotypes of M. leprae from nasal secretions (NS) and skin biopsy (SB) in the same patient, supplementing conventional epidemiology to gain insight into the infection of leprosy in Fortaleza, Brazil. Methods: The sample consisted of 38 newly diagnosed leprosy patients attending the National Reference Center of Dermatology Dona Libania (CDERM), in Fortaleza, who tested positive for M. leprae by PCR in DNA extracts of nasal secretions. DNA was also extracted from skin biopsy (SB) scrapings of each patient and used for multiplex PCR amplification of M. leprae VNTR loci. The number of repeats at 15 loci were determined by the fragment length analysis method. Results: Locus VNTR genotypes were achieved in 38 NS, and in 38 SB specimens. M. leprae strains differed in their genotypes in paired specimens in all but two of 38 patients. The genotype similarity in the remainder ranged from 53% to 87%. Conclusion: M. leprae 15 VNTR loci genotypes of paired nasal and biopsy skin samples from five patients were identical, while as many as seven loci differed in the 33 other patients. When the NS and biopsy genotypes were pooled and compared, it was found that there was a great variability among different VNTR markers. It is important to investigate other molecular markers suitable for typing genetic variations of the bacilli.


Asunto(s)
Biopsia/métodos , Lepra/microbiología , Repeticiones de Minisatélite , Mycobacterium leprae/genética , Nariz/microbiología , Piel/patología , Brasil/epidemiología , Estudios Transversales , ADN Bacteriano/genética , Enfermedades Endémicas , Variación Genética , Genotipo , Humanos , Lepra/diagnóstico , Mycobacterium leprae/clasificación , Mycobacterium leprae/aislamiento & purificación , Reacción en Cadena de la Polimerasa , Polimorfismo de Nucleótido Simple , Piel/microbiología
16.
Med Mal Infect ; 45(9): 383-93, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-26428602

RESUMEN

Leprosy is an infectious disease that has now been reported for more than 2000 years. The leprosy elimination goal set by the World Health Organization (WHO), i.e. a global prevalence rate <1 patient per 10,000 population, was achieved in the year 2000, but more than 200,000 new case patients are still reported each year, particularly in India, Brazil, and Indonesia. Leprosy is a specific infection: (i) it is a chronic infection primarily affecting the skin and peripheral nerves, (ii) Mycobacterium leprae is one of the last bacterial species of medical interest that cannot be cultured in vitro (mainly because of its reductive genome evolution), and (iii) transmission and pathophysiological data is still limited. The various presentations of the disease (Ridley-Jopling and WHO classifications) are correlated with the patient's immune response, bacillary load, and by the delay before diagnosis. Multidrug therapy (dapsone, rifampicin, with or without clofazimine) has been recommended since 1982 as the standard treatment of leprosy; 6 months for patients presenting with paucibacillary leprosy and 12 months for patients presenting with multibacillary leprosy. The worldwide use of leprosy drugs started in the 1980s and their free access since 1995 contributed to the drastic decline in the number of new case patients. Resistant strains are however emerging despite the use of multidrug therapy; identifying and monitoring resistance is still necessary.


Asunto(s)
Lepra , Anticuerpos Antibacterianos/sangre , Técnicas Bacteriológicas , Biopsia , Clofazimina/uso terapéutico , Dapsona/uso terapéutico , Farmacorresistencia Bacteriana , Utilización de Medicamentos , Genoma Bacteriano , Salud Global , Historia del Siglo XVI , Historia del Siglo XVII , Historia del Siglo XVIII , Historia Antigua , Humanos , Leprostáticos/uso terapéutico , Lepra/diagnóstico , Lepra/tratamiento farmacológico , Lepra/epidemiología , Lepra/historia , Lepra/fisiopatología , Lepra/transmisión , Técnicas de Diagnóstico Molecular , Mycobacterium leprae/clasificación , Mycobacterium leprae/efectos de los fármacos , Mycobacterium leprae/aislamiento & purificación , Mycobacterium leprae/fisiología , Filogenia , Prevalencia , Rifampin/uso terapéutico , Factores de Riesgo
17.
PLoS Negl Trop Dis ; 9(10): e0004141, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26441080

RESUMEN

BACKGROUND: Between 20 and 30 bacteriologically confirmed cases of leprosy are diagnosed each year at the French National Reference Center for mycobacteria. Patients are mainly immigrants from various endemic countries or living in French overseas territories. We aimed at expanding data regarding the geographical distribution of the SNP genotypes of the M. leprae isolates from these patients. METHODOLOGY/PRINCIPAL FINDINGS: Skin biopsies were obtained from 71 leprosy patients diagnosed between January 2009 and December 2013. Data regarding age, sex and place of birth and residence were also collected. Diagnosis of leprosy was confirmed by microscopic detection of acid-fast bacilli and/or amplification by PCR of the M. leprae-specific RLEP region. Single nucleotide polymorphisms (SNP), present in the M. leprae genome at positions 14 676, 1 642 875 and 2 935 685, were determined with an efficiency of 94% (67/71). Almost all patients were from countries other than France where leprosy is still prevalent (n = 31) or from French overseas territories (n = 36) where leprosy is not totally eradicated, while only a minority (n = 4) was born in metropolitan France but have lived in other countries. SNP type 1 was predominant (n = 33), followed by type 3 (n = 17), type 4 (n = 11) and type 2 (n = 6). SNP types were concordant with those previously reported as prevalent in the patients' countries of birth. SNP types found in patients born in countries other than France (Comoros, Haiti, Benin, Congo, Sri Lanka) and French overseas territories (French Polynesia, Mayotte and La Réunion) not covered by previous work correlated well with geographical location and history of human settlements. CONCLUSIONS/SIGNIFICANCE: The phylogenic analysis of M. leprae strains isolated in France strongly suggests that French leprosy cases are caused by SNP types that are (a) concordant with the geographic origin or residence of the patients (non-French countries, French overseas territories, metropolitan France) or (b) more likely random in regions where diverse migration flows occurred.


Asunto(s)
Variación Genética , Genotipo , Lepra/microbiología , Mycobacterium leprae/clasificación , Mycobacterium leprae/genética , Filogeografía , Polimorfismo de Nucleótido Simple , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Emigrantes e Inmigrantes , Femenino , Francia/epidemiología , Humanos , Lepra/epidemiología , Masculino , Persona de Mediana Edad , Mycobacterium leprae/aislamiento & purificación , Piel/microbiología , Adulto Joven
18.
PLoS Negl Trop Dis ; 9(9): e0004045, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26360617

RESUMEN

Recent reports have suggested that leprosy originated in Africa, extended to Asia and Europe, and arrived in the Americas during European colonization and the African slave trade. Due to colonization, the contemporary Colombian population is an admixture of Native-American, European and African ancestries. Because microorganisms are known to accompany humans during migrations, patterns of human migration can be traced by examining genomic changes in associated microbes. The current study analyzed 118 leprosy cases and 116 unrelated controls from two Colombian regions endemic for leprosy (Atlantic and Andean) in order to determine possible associations of leprosy with patient ancestral background (determined using 36 ancestry informative markers), Mycobacterium leprae genotype and/or patient geographical origin. We found significant differences between ancestral genetic composition. European components were predominant in Andean populations. In contrast, African components were higher in the Atlantic region. M. leprae genotypes were then analyzed for cluster associations and compared with the ancestral composition of leprosy patients. Two M. leprae principal clusters were found: haplotypes C54 and T45. Haplotype C54 associated with African origin and was more frequent in patients from the Atlantic region with a high African component. In contrast, haplotype T45 associated with European origin and was more frequent in Andean patients with a higher European component. These results suggest that the human and M. leprae genomes have co-existed since the African and European origins of the disease, with leprosy ultimately arriving in Colombia during colonization. Distinct M. leprae strains followed European and African settlement in the country and can be detected in contemporary Colombian populations.


Asunto(s)
Grupos de Población Continentales , Enfermedades Endémicas , Lepra/epidemiología , Lepra/microbiología , Mycobacterium leprae/clasificación , Mycobacterium leprae/genética , Adolescente , Adulto , Anciano , Análisis por Conglomerados , Colombia/epidemiología , Femenino , Haplotipos , Humanos , Masculino , Persona de Mediana Edad , Mycobacterium leprae/aislamiento & purificación , Filogenia , Homología de Secuencia , Adulto Joven
19.
PLoS One ; 10(5): e0124282, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25970602

RESUMEN

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.


Asunto(s)
Genes Bacterianos , Genoma Bacteriano , Lepra Lepromatosa/historia , Mycobacterium leprae/genética , Adulto , Radioisótopos de Carbono , Peroné/microbiología , Peroné/patología , Genotipo , Historia Medieval , Humanos , Lepra Lepromatosa/microbiología , Lepra Lepromatosa/patología , Lípidos/aislamiento & purificación , Masculino , Huesos Metatarsianos/microbiología , Huesos Metatarsianos/patología , Mycobacterium leprae/clasificación , Mycobacterium leprae/aislamiento & purificación , Mycobacterium leprae/metabolismo , Osteología , Reacción en Cadena de la Polimerasa , Polimorfismo de Nucleótido Simple , Análisis de Secuencia de ADN , Astrágalo/microbiología , Astrágalo/patología , Reino Unido
20.
BMC Genomics ; 15: 270, 2014 Apr 08.
Artículo en Inglés | MEDLINE | ID: mdl-24708363

RESUMEN

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.


Asunto(s)
Genoma Bacteriano , Lepra/microbiología , Mycobacterium leprae/genética , Arqueología , Huesos/microbiología , Epidemias , Evolución Molecular , Genotipo , Historia del Siglo XV , Historia del Siglo XVI , Historia Medieval , Humanos , Lepra/epidemiología , Lepra/historia , Mycobacterium leprae/clasificación , Mycobacterium leprae/aislamiento & purificación , Osteología , Filogenia , Polimorfismo de Nucleótido Simple , Análisis de Secuencia de ADN , Esqueleto , Reino Unido/epidemiología
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