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1.
J Invest Dermatol ; 137(12): 2544-2551, 2017 12.
Artículo en Inglés | MEDLINE | ID: mdl-28842327

RESUMEN

Although genome-wide association studies have greatly advanced our understanding of the contribution of common noncoding variants to leprosy susceptibility, protein-coding variants have not been systematically investigated. We carried out a three-stage genome-wide association study of protein-coding variants in Han Chinese, of whom were 7,048 leprosy patients and 14,398 were healthy control subjects. Seven coding variants of exome-wide significance were discovered, including two rare variants: rs145562243 in NCKIPSD (P = 1.71 × 10-9, odds ratio [OR] = 4.35) and rs149308743 in CARD9 (P = 2.09 × 10-8, OR = 4.75); three low-frequency variants: rs76418789 in IL23R (P = 1.03 × 10-10, OR = 1.36), rs146466242 in FLG (P = 3.39 × 10-12, OR = 1.45), and rs55882956 in TYK2 (P = 1.04 × 10-6, OR = 1.30); and two common variants: rs780668 in SLC29A3 (P = 2.17 × 10-9, OR = 1.14) and rs181206 in IL27 (P = 1.08 × 10-7, OR = 0.83). Discovered protein-coding variants, particularly low-frequency and rare ones, showed involvement of skin barrier and endocytosis/phagocytosis/autophagy, in addition to known innate and adaptive immunity, in the pathogenesis of leprosy, highlighting the merits of protein-coding variant studies for complex diseases.


Asunto(s)
Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Lepra/genética , Polimorfismo de Nucleótido Simple , Alelos , Grupo de Ascendencia Continental Asiática , Autofagia , Proteínas Adaptadoras de Señalización CARD/genética , Estudios de Casos y Controles , China , Estudios de Cohortes , Endocitosis , Exoma , Femenino , Frecuencia de los Genes , Variación Genética , Genotipo , Humanos , Lepra/etnología , Masculino , Fagocitosis , Reproducibilidad de los Resultados , Piel/metabolismo
2.
Lepr Rev ; 87(1): 109-12, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-27255065

RESUMEN

The cross-immunity between tuberculosis and leprosy is unknown. The aim of this pilot study was to evaluate the occurrence of Mycobacterium tuberculosis and M. leprae infection in Marshallese adult volunteers in Springdale, Arkansas, U.S.A., a population that experiences high rates of leprosy and tuberculosis. We used immunodiagnostic testing for tuberculosis and leprosy infection and found significant prevalence of latent tuberculosis infection (19.0%), and asymptomatic Mycobacterium leprae infection (22.2%). We found a negative association between presence of antibodies to Mycobacterium leprae and a positive interferon-γ release assay for Mycobacterium tuberculosis infection, prevalence odds ratio = 0.1 (95% CI = 0.0, 0.9). Although these findings require confirmation on a larger scale, they are supportive of the existence of cross-immunity.


Asunto(s)
Lepra/epidemiología , Tuberculosis/epidemiología , Adolescente , Adulto , Anciano , Arkansas/epidemiología , Humanos , Lepra/etnología , Persona de Mediana Edad , Proyectos Piloto , Tuberculosis/etnología , Adulto Joven
3.
Int J Rheum Dis ; 19(10): 1024-1031, 2016 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26250118

RESUMEN

BACKGROUND: Leprosy patients may present several osteoarticular complaints, which require further evaluation of inflammatory diseases, such as rheumatoid arthritis (RA). Therefore, an adequate clinical assessment in addition to testing for rheumatoid factors (RF) and anticyclic citrullinated peptide antibodies (anti-CCP), can be useful in order to establish the correct diagnosis. METHOD: In this study, the relation of RF and anti-CCP with rheumatological manifestations was evaluated in 97 leprosy patients from Southern Brazil. The results were compared to RA patients and healthy controls from the same geographical area and ethnic background. RESULTS: Neuropathy was observed in 71.1% and arthritis in 35.1% of the leprosy patients. A high frequency of RF positivity was observed among the leprosy patients (41.2%, 40/97), with RF immunoglobulin A (IgA) significantly associated with arthritis (OR = 7.9, 95% CI = 1.5-40.6 P = 0.008). Anti-CCP was observed in 9.3% (9/97) of the patients, with anti-CCP2 being the most frequent subtype. Only 4.1% (4/97) of the patients were RF and anti-CCP concomitantly positive. RF IgM showed a significant association with leprosy when compared to healthy controls (P < 0.0001) whereas for anti-CCP2 no significant results were observed (P = 0.0585). However, both biomarkers showed a strong association with RA when compared to leprosy in patients from the same geographical area and ethnic background (anti-CCP2 OR = 38.6; 95% CI = 16.49-90.26; P < 0.0001 and RF IgM OR = 4.51; 95% CI = 2.62-7.77; P < 0.0001). CONCLUSION: Due to the similarity of some rheumatological manifestations in leprosy with other inflammatory diseases, such as RA, clinical and laboratorial evaluation of affected patients must be carefully assessed in order to achieve proper diagnosis and treatment.


Asunto(s)
Artritis Reumatoide/inmunología , Inmunoglobulina M/sangre , Lepra/inmunología , Péptidos Cíclicos/inmunología , Factor Reumatoide/sangre , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Artritis Reumatoide/sangre , Artritis Reumatoide/diagnóstico , Artritis Reumatoide/etnología , Biomarcadores/sangre , Brasil/epidemiología , Estudios de Casos y Controles , Femenino , Humanos , Lepra/sangre , Lepra/diagnóstico , Lepra/etnología , Modelos Logísticos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Valor Predictivo de las Pruebas , Factores de Riesgo , Adulto Joven
4.
Int J Dermatol ; 55(1): 65-9, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26235265

RESUMEN

BACKGROUND: A significant association between single nucleotide polymorphisms in NOD2, C13orf31, and CCDC122 genes and leprosy has been reported in a previous genome-wide association study of leprosy in the Chinese Han population. However, it remains unknown whether this association exists among the Chinese Yi population. The aim of this study was to investigate whether single nucleotide polymorphisms in NOD2, C13orf31, and CCDC122 genes are associated with leprosy among the Chinese Yi population in China. METHODS: We genotyped rs9302752, rs7194886, rs8057341, and rs3135499 in the NOD2 gene; rs3764147 and rs10507522 in the C13orf31 gene; and rs3088362 and rs9533634 in the CCDC122 gene in a Chinese Yi cohort comprised of 319 patients with leprosy and 355 ethnic-matched controls. The differences between the patients and healthy controls were analyzed using chi-squared analysis. RESULTS: Significant differences of rs3135499 in NOD2, rs3764147 and rs10507522 in C13orf31, and rs3088362 and rs9533634 in CCDC122 were observed between the patients and the healthy control groups in the cohort. The allelic P values and odd ratios were as follows: rs3135499, 1.0 × 10(-8) and 2.55; rs3764147, 1.7 × 10(-7) and 1.88; rs10507522, 1.16 × 10(-5) and 1.95; rs3088362, 8.2 × 10(-4) and 1.51; rs9533634, 5.34 × 10(-5) and 1.73. No significant differences were found in the distributions of rs9302752, rs7194886, and rs8057341 between the patients and healthy controls. CONCLUSIONS: We demonstrated that genetic variants in the NOD2, C13orf31, and CCDC122 genes are closely associated with leprosy among the Chinese Yi population, which implicates the pathogenic role of NOD2, C13orf31, and CCDC122 genes in a different ethnicity.


Asunto(s)
Grupo de Ascendencia Continental Asiática/genética , Predisposición Genética a la Enfermedad/epidemiología , Variación Genética , Lepra/genética , Proteína Adaptadora de Señalización NOD2/genética , Adulto , Factores de Edad , Alelos , Estudios de Casos y Controles , China/epidemiología , Intervalos de Confianza , Femenino , Estudio de Asociación del Genoma Completo , Genotipo , Humanos , Incidencia , Lepra/etnología , Lepra/fisiopatología , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Fenotipo , Polimorfismo de Nucleótido Simple , Factores Sexuales , Adulto Joven
5.
J Dermatol Sci ; 80(2): 133-41, 2015 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-26360011

RESUMEN

BACKGROUND: Leprosy is an ancient chronic infection caused by Mycobacterium leprae. Onset of leprosy was highly affected by host nutritional condition and energy production, (partially) due to genomic loss and parasitic life style of M. leprae. The optic atrophy 1 (OPA1) gene plays an essential role in mitochondria, which function in cellular energy supply and innate immunity. OBJECTIVE: To investigate the potential involvement of OPA1 in leprosy. METHODS: We analyzed 7 common genetic variants of OPA1 in 1110 Han Chinese subjects with and without leprosy, followed by mRNA expression profiling and protein-protein interaction (PPI) network analysis. RESULTS: We observed positive associations between OPA1 variants rs9838374 (Pgenotypic=0.003) and rs414237 (Pgenotypic=0.002) with lepromatous leprosy. expression quantitative trait loci (eQTL) analysis showed that the leprosy-related risk allele C of rs414237 is correlated with lower OPA1 mRNA expression level. Indeed, we identified a decrease of OPA1 mRNA expression in both with patients and cellular model of leprosy. In addition, the PPI analysis showed that OPA1 protein was actively involved in the interaction network of M. leprae induced differentially expressed genes. CONCLUSION: Our results indicated that OPA1 variants confer risk of leprosy and may affect OPA1 expression, mitochondrial function and antimicrobial pathways.


Asunto(s)
Grupo de Ascendencia Continental Asiática/genética , GTP Fosfohidrolasas/genética , Lepra/genética , Polimorfismo de Nucleótido Simple , Adolescente , Adulto , Estudios de Casos y Controles , Niño , China/epidemiología , Femenino , GTP Fosfohidrolasas/metabolismo , Perfilación de la Expresión Génica/métodos , Frecuencia de los Genes , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Haplotipos , Humanos , Lepra/diagnóstico , Lepra/enzimología , Lepra/etnología , Lepra/microbiología , Masculino , Persona de Mediana Edad , Fenotipo , Mapas de Interacción de Proteínas , Sitios de Carácter Cuantitativo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Medición de Riesgo , Factores de Riesgo , Adulto Joven
7.
Fontilles, Rev. leprol ; 30(2): 159-177, mayo-ago. 2015. ilus, tab
Artículo en Español | IBECS | ID: ibc-144141

RESUMEN

Resulta fundamental revisar y comprender la importancia relativa de los factores percibidos por los afectados de lepra como obstáculos que les impiden completar el número de dosis requeridas en el tiempo necesario para optimizar la adherencia a la multiterapia (MDT). Objetivo: Para explorar los factores personales, familiares, sociales, comunitarios, de actitud, prácticos, geográficos, culturales y tradicionales que pueden influenciar la adherencia al tratamiento, se llevó a cabo un estudio en dos fases identificando los temas mediante grupos focales y la correspondiente clasificación de los mismos. Métodos: Mediante una entrevista con lista de comprobación se recopilaron las perspectivas de 895 encuestados (320 afectados por lepra que no pudieron completar el tratamiento, 302 de sus “cabezas de familia” y 273 de sus miembros comunitarios) en cuatro estados de la India, p. ej. Andhra Pradesh (Salur), Chhattisgarh (Chandkhuri), Maharashtra (Kothara) y Uttar Pradesh (Barabanki). Resultados: Los hallazgos sugieren que percibir cambios positivos en sus síntomas, así como no percibir mejoría puede conllevar a no completar la MDT. Los problemas con la planificación y el gasto del transporte también son temas clave. Un mejor control de las expectativas de las personas afectadas por lepra y la reducción de la carga del tratamiento también pueden ser estrategias importantes. La importancia del estigma y la pobreza se percibieron a través de varios temas, ninguno de los cuales fue particularmente clasificado como muy prioritario. Conclusiones: La naturaleza y diversidad de los temas percibidos por los encuestados en cada una de las regiones, sugiere que los determinantes de adherencia son complejos y multifactoriales. Se recomiendan más planteamientos comunitarios con una mejor coordinación


To maximise successful completion of multi-drug therapy (MDT) and optimise treatment outcomes for people with leprosy, it is vital to understand the relative importance of perceived factors which prevent them from completing the required number of doses in time. Objective: To explore personal, family, social, community, attitudinal, practical, geographical, cultural and traditional factors which may influence adherence to treatment, a two-phase study was undertaken comprising issue identification via focus groups, and a ranking exercise via individual interview. Study Design: The perspectives of 895 respondents (320 people affected by leprosy who were not able to complete treatment, 302 of their ‘operational heads of family’, and 273 of their nearby community members) across four states of India namely i.e. Andhra Pradesh (Salur), Chhattisgarh (Chandkhuri), Maharashtra (Kothara) and Uttar Pradesh (Barabanki) were collected, using a checklist interview method. Results: Findings suggest that seeing positive changes in their symptoms as well as not seeing improvement can lead to non-completion of MDT. Problems with scheduling and travel expenses were also key issues. Better management of the expectations of people affected by leprosy and reducing the burden of treatment may be important strategies. The importance of stigma and poverty were noted through a number of issues, none of which were particularly highly ranked. Conclusions: The nature and diversity of perceived issues identified across respondent type and particularly region, suggest that the determinants of adherence are complex and multi-factorial. More community based approaches with greater coordination at the community level are recommended


Asunto(s)
Femenino , Humanos , Masculino , Lepra/diagnóstico , Lepra/prevención & control , Lepra/terapia , Terapéutica/psicología , Terapéutica/estadística & datos numéricos , Terapéutica/tendencias , Lepra/etnología , Lepra/etiología , Terapéutica , Terapéutica/economía
8.
N Z Med J ; 128(1414): 9-14, 2015 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-26117385

RESUMEN

AIM: To examine the current epidemiological trends of leprosy in New Zealand and raise awareness of this disease in the health professional community. METHOD: Epidemiological data of leprosy, a notifiable disease in New Zealand, was accessed for the 10 year time period 2004 to 2013. Using an illustrative case as an introduction, all 38 case reports from the study period are summarised. RESULTS: Most cases of leprosy in New Zealand notified during the study period are immigrants from countries with endemic leprosy, reflecting the origin of disease. Delay to diagnosis is common. CONCLUSION: Leprosy remains a clinical problem in New Zealand. Cases are more likely to arise in geographical areas with higher numbers of immigrants from endemic countries.


Asunto(s)
Enfermedades Endémicas , Lepra , Adolescente , Adulto , Anciano , Biopsia , Preescolar , Diagnóstico Tardío/prevención & control , Emigrantes e Inmigrantes/estadística & datos numéricos , Enfermedades Endémicas/prevención & control , Enfermedades Endémicas/estadística & datos numéricos , Femenino , Humanos , Lepra/diagnóstico , Lepra/etnología , Lepra/fisiopatología , Lepra/terapia , Masculino , Mycobacterium leprae/aislamiento & purificación , Nueva Zelanda/epidemiología , Salud Pública/métodos , Salud Pública/estadística & datos numéricos , Salud Pública/tendencias , Estudios Retrospectivos , Piel/patología
9.
Int J Infect Dis ; 35: 1-2, 2015 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-25820095

RESUMEN

OBJECTIVE: Leprosy and tuberculosis (TB) are chronic granulomatous infectious diseases. As well as pathogen and environmental factors, host genetic factors make a substantial contribution to susceptibility to both diseases. More importantly, leprosy and TB also have pathogenic mechanisms and clinical features in common. In this study, the genetic association between leprosy and TB was investigated in a Chinese Han population. METHODS: A genetic association study that included 46 TB susceptibility single nucleotide polymorphisms (SNPs) was performed, involving 1150 leprosy cases and 1150 controls from the Chinese Han population. The Sequenom MassARRAY system was used. RESULTS: No significant association was found between the 46 SNPs and leprosy. Therefore, according to the present study, there is no shared susceptibility locus between leprosy and TB in the Chinese Han population. CONCLUSIONS: Although leprosy and TB have a number of similar characteristics, no shared susceptibility loci were found in the Chinese Han population. Thus, this study demonstrated that the genetic basis of the pathogenesis of the two diseases may vary greatly.


Asunto(s)
Lepra/genética , Polimorfismo de Nucleótido Simple , Tuberculosis/genética , Grupo de Ascendencia Continental Asiática/genética , Estudios de Casos y Controles , China/etnología , Femenino , Predisposición Genética a la Enfermedad , Humanos , Lepra/etnología , Masculino , Riesgo , Tuberculosis/etnología
10.
Lepr Rev ; 86(4): 328-34, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26964428

RESUMEN

BACKGROUND: Tribal populations are an underserved population group and access to health services is a major challenge for them. Since leprosy treatment is integrated with the general health services, identifying leprosy cases is not be easy in these settings and they remain as endemic reservoirs, unless greater efforts are made to reach them. METHODOLOGY: An active search operation was conducted in the tribal colonies in four pre-identified Health & Nutrition Clusters, Nellore district, Andhra Pradesh, India, in 2013. After a brief training, village health nurses and selected volunteers covered all the households, showing flash cards with photos of leprosy cases and enquiring if there was any resident with a similar condition. Suspects were listed and examined by the district leprosy supervisor and field coordinators from Damien Foundation. Follow up interviews were done after one year to assess the treatment completion rate. RESULTS: Village health workers covered 47,574 people living in the tribal colonies and identified 325 leprosy suspects. Among them, 70 were confirmed as new leprosy cases. The prevalence of previously undetected leprosy cases was found to be 14.7/10,000. Out of 70 cases, 19 (27%) were children, 35 (50%) were female, 32 (45.7%) were classified as MB leprosy, 6 (8.6%) had a leprosy reaction and 11 (15.7%) persons had Grade 2 disability at the time of diagnosis. The treatment completion rate was found to be 74% at the end of one year. CONCLUSION: The study reveals a very high burden of leprosy among the tribal population and demonstrates how resources can be mobilized from government, NGO and local community sources to promote early case detection among underserved population groups.


Asunto(s)
Lepra/etnología , Población Rural/estadística & datos numéricos , Adolescente , Adulto , Niño , Preescolar , Femenino , Humanos , India/epidemiología , India/etnología , Lepra/epidemiología , Masculino , Persona de Mediana Edad , Grupos de Población , Adulto Joven
11.
Genes Immun ; 16(2): 112-9, 2015 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-25521227

RESUMEN

Leprosy is a chronic infectious and neurological disease that is caused by infection of Mycobacterium leprae (M. leprae). A recent genome-wide association study indicated a suggestive association of LRRK2 genetic variant rs1873613 with leprosy in Chinese population. To validate this association and further identify potential causal variants of LRRK2 with leprosy, we genotyped 13 LRRK2 variants in 548 leprosy patients and 1078 healthy individuals from Yunnan Province and (re-)analyzed 3225 Han Chinese across China. Variants rs1427267, rs3761863, rs1873613, rs732374 and rs7298930 were significantly associated with leprosy per se and/or paucibacillary leprosy (PB). Haplotype A-G-A-C-A was significantly associated with leprosy per se (P=0.018) and PB (P=0.020). Overexpression of the protective allele (Thr2397) of rs3761863 in HEK293 cells led to a significantly increased nuclear factor of activated T-cells' activity compared with allele Met2397 after lipopolysaccharides stimulation. Allele Thr2397 could attenuate 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine-induced autophagic activity in U251 cells. These data suggest that the protective effect of LRRK2 variant p.M2397T on leprosy might be mediated by increasing immune response and decreasing neurotoxicity after M. leprae loading. Our findings confirm that LRRK2 is a susceptible gene to leprosy in Han Chinese population.


Asunto(s)
Grupo de Ascendencia Continental Asiática/genética , Lepra/genética , Proteínas Serina-Treonina Quinasas/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Niño , Preescolar , Femenino , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Haplotipos , Humanos , Lepra/etnología , Proteína 2 Quinasa Serina-Treonina Rica en Repeticiones de Leucina , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Adulto Joven
12.
Lepr Rev ; 85(3): 170-6, 2014 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-25509717

RESUMEN

OBJECTIVES: Leprosy remains a public health concern in Malaysia and globally. We aim to review the characteristics of leprosy patients in a tertiary institution in urban Malaysia. DESIGN: This is a case series of 27 leprosy patients who presented between 2008 and 2013. RESULTS: The majority of our patients consisted of male (74.1%), Malaysian (63.0%), blue collar workers (51.9%) and married (59.3%) patients; 48.1% had lepromatous leprosy. All except one of the patients presented with skin lesions, 25.9% had nerve involvement and 33.3% developed lepra reactions. Forty-four point four percent (44.4%) of the cases seen initially in the primary care setup were misdiagnosed. CONCLUSIONS: Doctors need to have a high index of suspicion for leprosy when patients present with suggestive skin, nerve or musculoskeletal lesions. Immigrants accounted for 37% of cases and these patients may become a reservoir of infection, thus accounting for the rise in incidence. An increasing trend in multibacillary cases may be attributed to the spread from migrants from countries with a high burden of leprosy.


Asunto(s)
Lepra/epidemiología , Viaje , Adulto , Anciano , Asia/epidemiología , Femenino , Humanos , Lepra/diagnóstico , Lepra/etnología , Malasia/epidemiología , Malasia/etnología , Masculino , Persona de Mediana Edad , Adulto Joven
13.
Int J Immunogenet ; 41(3): 231-5, 2014 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-24495190

RESUMEN

Leprosy is one of the most neglected infectious tropical diseases of the skin and the nerves caused by the intracellular pathogen Mycobacterium leprae. The inducible NOS isoform encoded by NOS2A plays a vital role in host defence against bacterial infections. The functional promoter polymorphisms in NOS2A are associated with various autoimmune and infectious diseases. We investigated the association of NOS2A variants with progression of leprosy in a Brazilian cohort including 221 clinically classified patients and 103 unrelated healthy controls. We observed a novel variant ss528838018A/G in the promoter region at position -6558. The other functional variants were observed with low frequency of minor allele (<0.005). NOS2A promoter variant (-954G/C) was not observed in Brazilian populations, and the new observed promoter variant (ss528838018A/G) as well as other promoter variants were not associated with any clinical forms of leprosy in the Brazilian populations.


Asunto(s)
Lepra/genética , Óxido Nítrico Sintasa de Tipo II/genética , Polimorfismo de Nucleótido Simple , Regiones Promotoras Genéticas , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Alelos , Brasil , Grupos de Población Continentales , Femenino , Frecuencia de los Genes , Genotipo , Humanos , Lepra/etnología , Lepra/microbiología , Masculino , Persona de Mediana Edad , Mycobacterium leprae/fisiología
14.
Med Anthropol ; 33(1): 6-20, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24383749

RESUMEN

With the promotion of community-based rehabilitation (CBR) as a solution to health-related issues across the global South, leprosy colonies have long been out of vogue for nongovernmental organizations and State institutions alike. Such colonies, however, have endured. As is being increasingly recognized by those working in the leprosy field, such places have played a particular role not only in the provision of leprosy-related care but also in forging new and collective identities for people affected by leprosy that might otherwise not have been possible. In this article, I draw on ethnographic fieldwork in one such colony in coastal Andhra Pradesh, South India, and explore the values invested in it as a particular kind of place; its geographical location on the peripheries; and its architecture and layout (inspired in part by colonial sanatoriums), which have particular implications for how leprosy and its ramifications are constituted and managed.


Asunto(s)
Colonias de Leprosos , Lepra , Terapias Espirituales , Antropología Médica , Cristianismo , Humanos , India , Lepra/etnología , Lepra/rehabilitación , Lepra/terapia
15.
Artículo en Inglés | MEDLINE | ID: mdl-23760321

RESUMEN

BACKGROUND: Leprosy has been a major public-health problem in many developing countries for centuries. According to the National Leprosy Elimination Programme report of March 2012, there were a total of about 0.13 million cases of leprosy in India, 9.7% of which were children. Numerous studies have investigated child leprosy amongst reported cases however, studies pertaining to proportion and characteristics of undetected childhood cases in the community are very few. AIM: To examine the clinical, bacteriological, and histopathological characteristics of newly detected child leprosy cases in the community. METHODS: The population survey conducted from June to September 2007 and the defined rural areas, which included five primary health centers of Panvel Taluka, in Raigad district and urban areas, which included M-east ward of the municipal corporation of greater Mumbai of western Maharashtra, India. RESULTS: House-to-house survey yielded 32 and 37 so far, undetected child cases of leprosy in the rural and urban region, and the prevalence rate was 10.5 and 1.5 per 10,000, respectively. The age of child leprosy cases detected, ranged from 3 to 14 years with a mean of 10.06 ± 3.35 years in the rural and 9.97 ± 3.12 years in the urban area. Most of the cases were paucibacillary (62%). A large proportion of children (49%) had single skin lesion (SSL). Of the 19 SSL cases examined histopathologically, 15 (99%) showed features of borderline tuberculoid, 1 (5%) borderline lepromatous and 3 (16%) had indeterminate type of leprosy. Tuberculoid leprosy was not seen in any, indicating less likelihood of self-healing. Overall, three cases had deformity (grade 1 = 1 and grade 2 = 2) and 31% of multibacillary cases were smear positive. CONCLUSION: The clinical, bacteriological, and histopathological characteristics of newly detected child cases in the community evidently indicate the grave nature of the problem of undetected child leprosy, recent active transmission, and highlight implications on individual patients and the community. KEY MESSAGE: Most of the cases were paucibacillary (62%). A large proportion of children (49%) had SSL and (55%) had it on the face followed by arms and leg (27%) and trunk (17%). The mean duration of symptoms exceeded one year which can be attributed to poor knowledge of leprosy or barriers in access to health care or its utilization.


Asunto(s)
Lepra/diagnóstico , Lepra/etnología , Vigilancia de la Población/métodos , Población Rural , Población Urbana , Adolescente , Niño , Preescolar , Femenino , Humanos , India/etnología , Lepra/microbiología , Masculino
16.
Ann Dermatol Venereol ; 140(5): 347-52, 2013 May.
Artículo en Francés | MEDLINE | ID: mdl-23663706

RESUMEN

BACKGROUND: There is no official leprosy register in France. The last epidemiological survey on leprosy in metropolitan France was done between 1995 and 1998. We performed a new epidemiological study of leprosy in metropolitan France in 2009 and 2010. PATIENTS AND METHODS: We contacted 85 dermatology and infectious disease units by e-mail or by telephone in order to determine the number of leprosy patients either being followed up or newly diagnosed in 2009 and 2010. RESULTS: The response rate was 87%. In 2010, 127 patients were being followed up in metropolitan France, mostly at dermatology units (78%). Seventy-five patients were on anti-bacillary treatment and the prevalence was 0.011/10,000. There were 39 new cases diagnosed in 2009 and 2010 (mean 19 cases/year) (low case-detection rate: 0.003 per 10,000 inhabitants). Among the new cases, seven patients (18%) were of French origin, with two from metropolitan France and five from French overseas territories. DISCUSSION: Our study confirms the persistence of imported leprosy in France and shows no significant decrease in the number of new cases since 1998 (19 vs. 18 new cases/year) or in disease prevalence (0.013 vs. 0.011 per 10,000 inhabitants). This prevalence is very far removed from the one per 10,000 inhabitants proposed by the World Health Organization as the criteria for endemic disease. Most patients in our survey were immigrants (82%). Lepromatous forms (46%) were more frequent than the tuberculoid forms (33%). All patients had either travelled to or lived in areas of high leprosy prevalence, including metropolitan subjects. CONCLUSION: Leprosy remains present in metropolitan France, and it is still important to continue teaching about it at medical faculties in order to ensure diagnosis of new patients as early as possible.


Asunto(s)
Lepra/epidemiología , Adolescente , Adulto , África del Sur del Sahara/etnología , Anciano , Asia Occidental/etnología , Niño , Dermatología , Emigrantes e Inmigrantes/estadística & datos numéricos , Femenino , Francia/epidemiología , Encuestas Epidemiológicas , Departamentos de Hospitales/estadística & datos numéricos , Hospitales Universitarios/estadística & datos numéricos , Humanos , Islas del Oceano Índico/etnología , Infectología , Leprostáticos/uso terapéutico , Lepra/tratamiento farmacológico , Lepra/etnología , Masculino , Persona de Mediana Edad , Prevalencia , Estudios Retrospectivos , América del Sur/etnología , Viaje , Población Urbana/estadística & datos numéricos , Adulto Joven
17.
Hum Genet ; 132(6): 629-40, 2013 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-23423485

RESUMEN

The complement system plays multiple roles in host defense against infection and is supposed to confer genetic susceptibility to leprosy. We aimed to examine whether genetic variants of the Ficolin-2 (FCN2), Mannose-binding lectin (MBL2) and Complement factor H (CFH) genes, which are involved in activation and regulation of the complement system, are associated with leprosy in Han Chinese from Southwest China. 527 leprosy patients and 583 matched controls were recruited from Yunnan Province, China, and were analyzed in this study. We sequenced the promoter region of the FCN2 and MBL2 genes and exon 8 of the FCN2 gene and genotyped three tag SNPs of the CFH gene. Association analysis was performed to discern potential effect of these three genes with leprosy and its subtypes. Luciferase assay was used to characterize the role of different promoter alleles of the FCN2 and MBL2 genes. Genetic variants of FCN2 (rs3811140 and rs7851696), MBL2 (rs11003125, rs7100749, rs11003124 and rs7096206) and CFH (rs1065489 and rs3753395) were significantly associated with leprosy and its subtypes. Haplotypes/genotypes representing low FCN2 and MBL2 transcriptional activity conferred risk to paucibacillary leprosy. Our data confirmed the expected positive association of complement genes with leprosy susceptibility and clinical outcomes in Han Chinese.


Asunto(s)
Grupo de Ascendencia Continental Asiática , Factor H de Complemento/genética , Lectinas/genética , Lepra/genética , Lectina de Unión a Manosa/genética , Estudios de Casos y Controles , China , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Humanos , Lepra/etnología , Polimorfismo de Nucleótido Simple
19.
J Clin Immunol ; 33(1): 210-9, 2013 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-22941510

RESUMEN

PURPOSE: Mycobacterium leprae exploits complement activation and opsonophagocytosis to infect phagocytes. M-ficolin is encoded by the FCN1 gene and initiates the lectin pathway on monocyte surfaces. We investigated FCN1 promoter polymorphisms that could be responsible for the high interindividual variability of M-ficolin levels and for modulating leprosy susceptibility. METHODS: We genotyped rs2989727 (-1981 G > A), rs28909068 (-791 G > A), rs10120023 (-542 G > A), rs17039495 (-399 G > A), rs28909976 (-271IndelT), rs10117466 (-144C > A) and rs10858293 (+33 T > G) in 400 controls and 315 leprosy patients from Southern Brazil, and in 296 Danish healthy individuals with known M-ficolin levels. RESULTS: Ten haplotypes were identified with sequence-specific PCR and/or haplotype-specific sequencing. We found evidence for a protective codominant additive effect of FCN1*-542A-144C with leprosy in Euro-Brazilians (P=0.003, PBf =0.021, OR=0.243 [CI95% =0.083-0.71]), which was independent of age, ethnic group and gender effects (P=0.029). There was a trend for a positive association of the -399A variant in Afro-Brazilians (P=0.022, PBf =0.154, OR=4.151 [CI95% =1.115-15.454], as well as for a negative association of the FCN1*3A haplotype with lepromatous leprosy, compared with less severe forms of the disease (P=0.016, PBf =0.112, OR=0.324 [CI95% =0.123-0.858]). Danish individuals with this haplotype presented M-ficolin levels higher than the population average of circa 1,000 ng/ml, and -542A-144C, which is able to modify the recognition of transcription factors in silico, occurred in individuals with levels under the 25 percentil (P=0.031). CONCLUSIONS: Our data provide the first evidence that FCN1 polymorphisms are associated with leprosy. M-ficolin may represent a novel key to understand the immunopathogenesis of M. leprae infection.


Asunto(s)
Predisposición Genética a la Enfermedad , Lectinas/genética , Lepra/genética , Lepra/inmunología , Polimorfismo de Nucleótido Simple , Adolescente , Adulto , Grupo de Ascendencia Continental Africana , Anciano , Anciano de 80 o más Años , Grupo de Ascendencia Continental Europea , Femenino , Genotipo , Humanos , Lepra/etnología , Lepra Lepromatosa/etnología , Lepra Lepromatosa/genética , Lepra Lepromatosa/inmunología , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple/genética , Polimorfismo de Nucleótido Simple/inmunología , Regiones Promotoras Genéticas , Adulto Joven
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