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1.
s.l; s.n; 2021. 10 p.
No convencional en Inglés | Sec. Est. Saúde SP, CONASS, HANSEN, SESSP-ILSLPROD, Sec. Est. Saúde SP, SESSP-ILSLACERVO, Sec. Est. Saúde SP | ID: biblio-1146801

RESUMEN

Leprosy is a prevalent disease in Brazil, which ranks as the country with the second highest number of cases in the world. The disease manifests in a spectrum of forms, and genetic differences in the host can help to elucidate the immunopathogenesis. For a better understanding of MICA association with leprosy, we performed a case­control and a family­based study in two endemic populations in Brazil. MICA and HLA­B alleles were evaluated in 409 leprosy patients and in 419 healthy contacts by PCR­SSOP­Luminex­based technology. In the familial study, analysis of 46 families was completed by direct sequencing of all exons and 3'/5'untranslated regions, using the Ilumina MiSeq platform. All data were collected between 2006 and 2009. Statistical analysis was performed using the Chi­square or Fisher's exact test together with a multivariate analysis. Family­based association was assessed by transmission disequilibrium test (TDT) software FBAT 2.0.4. We found associations between the haplotype MICA*002­HLA­B*35 with leprosy in both the per se and the multibacillary (MB) forms when compared to healthy contacts. The MICA allele *008 was associated with the clinical forms of paucibacillary (PB). Additionally, MICA*029 was associated with the clinical forms of MB. The association of MICA*029 allele (MICA­A4 variant) with the susceptibility to the MB form suggests this variant for the transmembrane domain of the MICA molecule may be a risk factor for leprosy. Two MICA and nine HLA­B variants were found associated with leprosy per se in the Colônia do Prata population. Linkage disequilibrium analysis revealed perfect linkage disequilibrium (LD) between HLA­B markers rs2596498 and rs2507992, and high LD (R2 = .92) between these and the marker rs2442718. This familial study demonstrates that MICA association signals are not independent from those observed for HLA­B. Our findings contribute the knowledge pool of the immunogenetics of Hansen's disease and reveals a new association of the MICA*029 allele(AU).


Asunto(s)
Humanos , Masculino , Femenino , Antígenos de Histocompatibilidad Clase I , Antígenos HLA-B , Lepra/genética , Lepra/inmunología , Polimorfismo Genético , Desequilibrio de Ligamiento , Factores de Riesgo , Predisposición Genética a la Enfermedad , Alelos , Lepra/transmisión
2.
PLoS Negl Trop Dis ; 14(9): e0008611, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32936805

RESUMEN

BACKGROUND: The aim of this study is to explore whether transmission of M. leprae has ceased in Spain, based upon the patterns and trends of notified cases. METHODOLOGY: Data on new cases reported to the National Leprosy Registry between the years 2003-2018 were extracted. In absence of detailed travel history, cases were considered "autochthonous" or "imported" based on whether they were born within or outside of Spain. These data were analyzed by age, sex, clinical type, country of origin, and location of residence at time of notification. PRINCIPAL FINDINGS: Data were available on 61 autochthonous and 199 imported cases since 2003. There were clear declines in incidence in both groups, and more imported than autochthonous cases every year since 2006. Autochthonous cases were more frequently multibacillary and had older age at diagnosis compared to imported cases. All the autochthonous cases had been born before 1985 and were more than 25 years old at diagnosis. Male-to-female ratio increased with time for autochthonous cases (except for the last time period). The imported cases originated from 25 countries, half of them from Brasil and Paraguay. Autochthonous cases were mainly distributed in the traditionally endemic regions, especially Andalucía and the eastern Mediterranean coast. CONCLUSIONS: Autochthonous and imported cases have different epidemiologic patterns in Spain. There was a clear decline in incidence rates of autochthonous disease, and patterns consistent with those reported from other regions where transmission has ceased. Autochthonous transmission of M. leprae is likely to have now effectively stopped in Spain.


Asunto(s)
Lepra/epidemiología , Lepra/transmisión , Adulto , Factores de Edad , Anciano , Femenino , Geografía , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Mycobacterium leprae/aislamiento & purificación , Factores Sexuales , España/epidemiología , Viaje
3.
PLoS Negl Trop Dis ; 14(9): e0008583, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32936818

RESUMEN

BACKGROUND: Subclinical infection with Mycobacterium leprae is one potential source of leprosy transmission, and post-exposure prophylaxis (PEP) regimens have been proposed to control this source. Because PEP trials require considerable investment, we applied a sensitive variation of the kinetic mouse footpad (MFP) screening assay to aid in the choice of drugs and regimens for clinical trials. METHODOLOGY/PRINCIPAL FINDINGS: Athymic nude mice were inoculated in the footpad (FP) with 6 x 103 viable M. leprae and treated by gastric gavage with a single dose of Rifampin (SDR), Rifampin + Ofloxacin + Minocycline (SD-ROM), or Rifapentine + Minocycline + Moxifloxacin (SD-PMM) or with the proposed PEP++ regimen of three once-monthly doses of Rifampin + Moxifloxacin (RM), Rifampin + Clarithromycin (RC), Rifapentine + Moxifloxacin (PM), or Rifapentine + Clarithromycin (PC). At various times post-treatment, DNA was purified from the FP, and M. leprae were enumerated by RLEP quantitative PCR. A regression analysis was calculated to determine the expected RLEP value if 99.9% of the bacilli were killed after the administration of each regimen. SDR and SD-ROM induced little growth delay in this highly susceptible murine model of subclinical infection. In contrast, SD-PMM delayed measurable M. leprae growth above the inoculum by 8 months. The four multi-dose regimens delayed bacterial growth for >9months post-treatment cessation. CONCLUSIONS/SIGNIFICANCE: The delay in discernable M. leprae growth post-treatment was an excellent indicator of drug efficacy for both early (3-4 months) and late (8-9 months) drug efficacy. Our data indicates that multi-dose PEP may be required to control infection in highly susceptible individuals with subclinical leprosy to prevent disease and decrease transmission.


Asunto(s)
Infecciones Asintomáticas/terapia , Leprostáticos/uso terapéutico , Lepra/tratamiento farmacológico , Mycobacterium leprae/efectos de los fármacos , Profilaxis Posexposición/métodos , Animales , Carga Bacteriana/efectos de los fármacos , Claritromicina/uso terapéutico , Combinación de Medicamentos , Lepra/transmisión , Ratones , Ratones Desnudos , Minociclina/uso terapéutico , Moxifloxacino/uso terapéutico , Mycobacterium leprae/crecimiento & desarrollo , Rifampin/análogos & derivados , Rifampin/uso terapéutico
4.
Trop Doct ; 50(4): 311-317, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32576099

RESUMEN

An observational pilot study was conducted to assess the nutritional status and morbidity profile of childhood contacts of leprosy in an endemic area (Chengalpattu) in India. A total of 70 such children were included in the study. Sociodemographic data were collected using a one-to-one interview method and the children were evaluated by dermatologists qualified in paediatric leprosy. The obtained data were computed. Three children were diagnosed to have leprosy through this study. Nutritional status assessment in these children demonstrated malnutrition, a common finding. Regular contact screening of children in endemic areas for early case detection, disability prevention and thereby prevention of community transmission is mandatory. Further research is needed concerning the role of malnutrition in children and its relation to morbidity in leprosy. The closeness and duration of contact of leprosy is also an important risk factor. Effective strategies to diagnose subclinical infection are needed.


Asunto(s)
Salud del Niño , Lepra/epidemiología , Lepra/transmisión , Salud Rural , Adolescente , Niño , Diagnóstico Precoz , Femenino , Humanos , India/epidemiología , Lepra/diagnóstico , Lepra/prevención & control , Masculino , Morbilidad , Estado Nutricional , Proyectos Piloto , Factores de Riesgo
5.
Int J Infect Dis ; 98: 6-13, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32553715

RESUMEN

OBJECTIVES: Understanding the nature of Mycobacterium leprae transmission is vital to implement better control strategies for leprosy elimination. The present study expands the knowledge of county-level strain diversity, distribution, and transmission patterns of leprosy in endemic provinces of China. METHODS: We genetically characterized 290 clinical isolates of M. leprae from four endemic provinces using variable number tandem repeats (VNTR) and single nucleotide polymorphisms (SNPs). Attained genetic profiles and cluster consequences were contrasted with geographical and migration features of leprosy at county levels. RESULTS: Considering the allelic variability of 17 VNTR loci by the discriminatory index, (GTA)9, (AT)17, (AT)15, (TA)18, (TTC)21, and (TA)10 are reported to be more highly polymorphic than other loci. The VNTR profile generated the low-density clustering pattern in the counties of Sichuan and Yunnan, whereas clusters have been observed from the isolates from Huayuan (N = 6), Yongding (N = 3), Zixing (N = 3), Chenxi (N = 2) and Zhongfang (N = 2) counties of Hunan, and Zhijin (N = 3), Anlong (N = 2), Zhenning (N = 2), and Xixiu (N = 2) counties of Guizhou. In some clusters, people's social relations have been observed between villages. From the 290 clinical isolates, the most predominantly reported SNP was 3K (278, 95.8%), followed by SNP 1D (10, 3.4%), which are typically observed to be predominant in China. We also detected the novel SNP 3J (2, 0.8%), which has not yet been reported in China. CONCLUSION: The clustering pattern of M. leprae indicates the transmission of leprosy still persists at county levels, suggesting that there is a need to implement better approaches for tracing the close contacts of leprosy patients.


Asunto(s)
Lepra/microbiología , Mycobacterium leprae/aislamiento & purificación , Alelos , China/epidemiología , Análisis por Conglomerados , ADN Bacteriano/genética , Genotipo , Geografía , Humanos , Lepra/epidemiología , Lepra/transmisión , Repeticiones de Minisatélite , Epidemiología Molecular , Mycobacterium leprae/clasificación , Mycobacterium leprae/genética , Filogenia , Polimorfismo de Nucleótido Simple
6.
Int J Infect Dis ; 96: 172-179, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-32371193

RESUMEN

BACKGROUND: Human-to-human transmission of Mycobacterium leprae among household contacts of active leprosy cases is significant, and surveillance of household contacts is vital to interrupting the transmission chain for this disease. This study was conducted to identify similarities in M. leprae strains, based on genomic single nucleotide polymorphisms (SNPs), among cases and their household contacts and in multicase families in order to decipher possible associations, transmission links, various clinical conditions of index cases that enhance person-to-person transmission, and timelines for transmission patterns. METHODS: PCR for M. leprae DNA detection (amplification of the Rlep gene) and SNP subtyping of M. leprae strains was performed for 61 index cases and one of their household contacts. Additionally, we studied six families with multiple cases of leprosy, to understand timelines of infectivity and its relation to severity of the disease in the index cases. RESULTS: Index cases with lepromatous (LL) and borderline lepromatous (BL) leprosy, together with a positive bacteriological index (BI) for M. leprae, result in a higher percentage of their contacts subclinically infected with M. leprae, with odds ratios (OR) of 6.6 (95% confidence interval (CI) 1.6-27.6) for BL and LL, and 7.07 (CI 1.41-35.41) for BI-positive index cases. 75% of the case-contact pairs had a similar SNP subtype of M. leprae. The timeline of infection in multicase families revealed that contacts were infected during the BI-positive period of the index case. CONCLUSION: Using molecular methods, we determined that positivity for M. leprae DNA in contacts of index leprosy cases was attributed to clinical characteristics of leprosy in the index cases. LL and BL forms of leprosy, together with positive BI, contributed to dissemination of infection to household contacts. In conclusion, we found a relationship between SNP subtypes within index case-contact pairs. This method can help decipher the transmission patterns and identify individuals at risk of contracting leprosy.


Asunto(s)
Lepra/epidemiología , Mycobacterium leprae/genética , Adolescente , Adulto , Composición Familiar , Femenino , Humanos , Lepra/microbiología , Lepra/transmisión , Masculino , Persona de Mediana Edad , Epidemiología Molecular , Mycobacterium leprae/clasificación , Mycobacterium leprae/aislamiento & purificación , Reacción en Cadena de la Polimerasa/métodos , Polimorfismo de Nucleótido Simple , Adulto Joven
7.
PLoS Negl Trop Dis ; 14(4): e0008276, 2020 04.
Artículo en Inglés | MEDLINE | ID: mdl-32339201

RESUMEN

Leprosy is a chronic infectious disease caused by Mycobacterium leprae (M. leprae) and the more recently discovered Mycobacterium lepromatosis (M. lepromatosis). The two leprosy bacilli cause similar pathologic conditions. They primarily target the skin and the peripheral nervous system. Currently it is considered a Neglected Tropical Disease, being endemic in specific locations within countries of the Americas, Asia, and Africa, while in Europe it is only rarely reported. The reason for a spatial inequality in the prevalence of leprosy in so-called endemic pockets within a country is still largely unexplained. A systematic review was conducted targeting leprosy transmission research data, using PubMed and Scopus as sources. Publications between January 1, 1945 and July 1, 2019 were included. The transmission pathways of M. leprae are not fully understood. Solid evidence exists of an increased risk for individuals living in close contact with leprosy patients, most likely through infectious aerosols, created by coughing and sneezing, but possibly also through direct contact. However, this systematic review underscores that human-to-human transmission is not the only way leprosy can be acquired. The transmission of this disease is probably much more complicated than was thought before. In the Americas, the nine-banded armadillo (Dasypus novemcinctus) has been established as another natural host and reservoir of M. leprae. Anthroponotic and zoonotic transmission have both been proposed as modes of contracting the disease, based on data showing identical M. leprae strains shared between humans and armadillos. More recently, in red squirrels (Sciurus vulgaris) with leprosy-like lesions in the British Isles M. leprae and M. lepromatosis DNA was detected. This finding was unexpected, because leprosy is considered a disease of humans (with the exception of the armadillo), and because it was thought that leprosy (and M. leprae) had disappeared from the United Kingdom. Furthermore, animals can be affected by other leprosy-like diseases, caused by pathogens phylogenetically closely related to M. leprae. These mycobacteria have been proposed to be grouped as a M. leprae-complex. We argue that insights from the transmission and reservoirs of members of the M. leprae-complex might be relevant for leprosy research. A better understanding of possible animal or environmental reservoirs is needed, because transmission from such reservoirs may partly explain the steady global incidence of leprosy despite effective and widespread multidrug therapy. A reduction in transmission cannot be expected to be accomplished by actions or interventions from the human healthcare domain alone, as the mechanisms involved are complex. Therefore, to increase our understanding of the intricate picture of leprosy transmission, we propose a One Health transdisciplinary research approach.


Asunto(s)
Reservorios de Enfermedades , Transmisión de Enfermedad Infecciosa , Lepra/transmisión , Lepra/veterinaria , Animales , Armadillos/microbiología , Salud Global , Humanos , Incidencia , Lepra/epidemiología , Mycobacterium/aislamiento & purificación , Mycobacterium leprae/aislamiento & purificación , Prevalencia , Sciuridae/microbiología
8.
Indian J Dermatol Venereol Leprol ; 86(2): 115-123, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-31975697

RESUMEN

With the worldwide implementation of WHO multidrug therapy in the 1980s, the global burden of leprosy has decreased. However, the annual new case detection rate around the world has remained nearly static over the past decade with India, Brazil, and Indonesia contributing the majority of these new cases. This has been attributed to the ongoing transmission of Mycobacterium leprae from existing untreated cases and partly to the intensive new case detection programs operative in endemic areas. The WHO has called for a "global interruption of transmission of leprosy by 2020". Targeted chemoprophylaxis of contacts may help bring down the number of new cases. The single-dose rifampicin currently in use for post-exposure prophylaxis (PEP) has limitations and so newer antileprosy drugs and regimens have been trialed for chemoprophylaxis. BCG re-vaccination in combination with chemoprophylaxis for the prevention of leprosy transmission has not been very encouraging. The use of the anti-phenolic glycolipid-1 (PGL-1) antibody test to detect subclinical cases and administer targeted chemoprophylaxis was unsuccessful owing to its low sensitivity and technical difficulties in a field setup. There is a pressing need for newer multidrug chemoprophylactic regimens using second-line antileprosy drugs. The Netherlands Leprosy Relief has proposed an enhanced PEP++ regimen. A simple but highly sensitive and specific serological test to detect subclinical cases at the field level needs to be developed. Although there are a number of challenges in the large-scale implementation of strategies to halt leprosy transmission, it is important to overcome these in order to move towards a "leprosy-free world."


Asunto(s)
Inmunoterapia/métodos , Leprostáticos/administración & dosificación , Lepra/prevención & control , Lepra/transmisión , Ensayos Clínicos como Asunto/métodos , Quimioterapia Combinada , Humanos , Inmunoterapia/tendencias , Lepra/epidemiología , Mycobacterium leprae/efectos de los fármacos , Mycobacterium leprae/aislamiento & purificación
9.
Dis Mon ; 66(7): 100899, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-31806242

RESUMEN

Leprosy is a bacterial infection causing severe disfigurement of the affected individual. It is considered as an ancient disease affecting humanity since thousands of years and also has tremendous stigma associated with it. It is known as a neglected tropical disease. In spite of all the efforts, the disease remains a major healthcare distress in many underdeveloped and developing countries like India and Brazil. Thus, to understand the disease and implement various strategies successfully, one need to understand the epidemiological aspect of the disease along with various operational factors influencing the epidemiological data. Thus, the present paper describes the various epidemiological facts and figures of leprosy along with the suggestions and measures to tackle this global ailment.


Asunto(s)
Lepra/epidemiología , Lepra/microbiología , Enfermedades del Sistema Nervioso Periférico/fisiopatología , Enfermedades Cutáneas Bacterianas/patología , Brasil/epidemiología , Niño , Femenino , Historia del Siglo XIX , Humanos , Incidencia , India/epidemiología , Lepra/historia , Lepra/transmisión , Masculino , Mycobacterium leprae/aislamiento & purificación , Enfermedades del Sistema Nervioso Periférico/etiología , Enfermedades del Sistema Nervioso Periférico/microbiología , Prevalencia , Enfermedades Cutáneas Bacterianas/etiología , Enfermedades Cutáneas Bacterianas/microbiología , Estigma Social
10.
Cad Saude Publica ; 35(10): e00014419, 2019.
Artículo en Portugués | MEDLINE | ID: mdl-31596392

RESUMEN

The study aimed to analyze the magnitude and sociodemographic profile of leprosy cases linked to household contact networks with overlapping of the disease in two Brazilian municipalities (counties), one in the North and the other in the Northeast, from 2001 to 2014. This was a cross-sectional, descriptive, analytical study based on primary and secondary data from new leprosy cases in Picos, Piauí State, and Rolim de Moura, Rondônia State. "Overlapping" was defined as new cases with the occurrence of at least one more leprosy case in the individual's household contact network. Each household contact network consisted of the index case (first reported case), co-prevalent cases (contacts that became new cases), and household contacts of the index case. A total of 437 new cases treated by the INTEGRAHANS North-Northeast and Piauí projects were assessed, of which 287 (65.7%) were in Picos and 150 (34.3%) in Rolim de Moura. Of all the cases assessed, 129 (44.9%) in Picos and 98 (65.3%) in Rolim de Moura reported overlapping. There were proportionally more females in Rolim de Moura (n = 95, 63.3%) and males in Picos (n = 147, 51.2%); in the 41-60-year age bracket (Rolim de Moura n = 70, 46.7%; Picos n = 115, 40.1%); with elementary schooling (Rolim de Moura n = 80, 54%; Picos n = 125, 44.5%); and individuals living in the same household with up to 3 persons in Rolim de Moura (n = 105, 70%) and with more than 4 persons in Picos (n = 287, 100%). Overlapping of leprosy cases in household contact networks was considerably high in the contexts analyzed here, displaying aspects of expanded vulnerability. This perspective should be considered and integrated into leprosy surveillance and control activities.


Asunto(s)
Lepra/epidemiología , Lepra/transmisión , Adolescente , Adulto , Brasil/epidemiología , Ciudades , Trazado de Contacto , Estudios Transversales , Composición Familiar , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Factores Socioeconómicos , Adulto Joven
11.
Vaccine ; 37(43): 6510-6517, 2019 10 08.
Artículo en Inglés | MEDLINE | ID: mdl-31500969

RESUMEN

BACKGROUND: Immunoprophylaxis with Bacillus Calmette-Guérin (BCG) vaccine is still the most effective intervention in the prevention of leprosy among household contacts (HHCs) of leprosy patients. METHODS: A retrospective cohort study using data of 5.061 HHCs for a period of 16 years (follow-up of 7 years per leprosy HHCs), evaluating the occurrence of disease as the main outcome and the presence or absence of BCG scars verified at the first evaluation. Statistical analyzes were performed using the relative risk, hazard ratio and survival curves by Kaplan-Meier test. RESULTS: A total of 92 contacts sickened, of which 41.3% (38/92) in the first year and 58.7% (54/92) in the course of the other years of follow-up. Of those who became sick, 62% (57/92) developed borderline tuberculoid (BT). The additional protective effect occurred for those who had 2 BCG scars at the first follow-up assessment (Relative Risk: 0.41; p = 0.007) when compared to those not previously exposed to the vaccine. The number of BCG scars examined at the first assessment (t0 = time zero) affected the occurrence of the outcome evidenced by the difference in survival curves throughout the follow-up (Log Rank, p = 0.041; Breslow, p = 0.012; Tarone-Ware, p = 0.020). Leprosy HHCs with 0 BCG scar at time zero (t0) have a shorter survival time (average time of 22 months between t0 and outcome) when compared to those with 2 BCG scars (average time of 36 months between t0 and outcome). CONCLUSIONS: Vaccination of healthy individuals without signs and symptoms of leprosy is extremely important because BCG vaccine has an additional protective effect in those cases with 2 BCG scars throughout follow-up. Reducing the risk of leprosy HHCs becoming sick depends on preventive actions such as immunoprophylaxis and index cases treatment.


Asunto(s)
Vacuna BCG/administración & dosificación , Composición Familiar , Lepra/prevención & control , Adolescente , Adulto , Brasil/epidemiología , Niño , Preescolar , Femenino , Estudios de Seguimiento , Humanos , Lactante , Recién Nacido , Lepra/transmisión , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Factores de Riesgo , Adulto Joven
12.
Cad Saude Publica ; 35(9): e00209518, 2019 09 09.
Artículo en Portugués | MEDLINE | ID: mdl-31508701

RESUMEN

The aim was to analyze the space-time trend in the proportion of contacts examined among those recorded, according to demographic profile of new leprosy cases in the State of Bahia, Brazil, in the 2003-2014 cohort. This was a state population-based ecological study with temporal and spatial analyses of the proportion of contacts examined among those recorded, according to characteristics of the reference leprosy case, based on the Information System for Notifiable Diseases of the Brazilian Ministry of Health. The time trend analysis was based on Poisson regression (Joinpoints). Spatial analysis used spatial autocorrelation by local indicators of spatial association. Over the course of the historical series, 52.9% (55,116/104,142) of the recorded contacts were examined, with lower proportions in persons < 60 years of age, indigenous individuals, and residents of large cities (especially the state capital Salvador). There was an upward trend in the proportion of contacts examined, less evident when the reference leprosy case was a male, black, living in the rural area, and in small towns or the state capital. Spatial distribution showed that the majority of the municipalities showed precarious performance, with clusters identified in the North and Far South of the state. Bahia shows precarious performance on contact surveillance, particular in conditions of greater social vulnerability. Additional strategies should be implemented in order to overcome the operational obstacles to contact surveillance, considered essential for interrupting leprosy transmission in the state.


Asunto(s)
Trazado de Contacto/estadística & datos numéricos , Lepra/prevención & control , Vigilancia de la Población/métodos , Adolescente , Adulto , Brasil/epidemiología , Estudios de Cohortes , Femenino , Humanos , Lepra/epidemiología , Lepra/transmisión , Masculino , Persona de Mediana Edad , Factores de Riesgo , Factores Socioeconómicos , Análisis Espacio-Temporal , Adulto Joven
13.
Rev Inst Med Trop Sao Paulo ; 61: e44, 2019 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-31531622

RESUMEN

Mycobacterium leprae is the primary causative agent of Hansen's disease or leprosy. Besides human beings, natural infection has been described in animals such as mangabey monkeys and armadillos. Leprosy is considered a global health problem and its complete pathogenesis is still unknown. As M. leprae does not grow in artificial media, armadillos have become the primary experimental model for leprosy, mimicking human disease including involvement of the peripheral nervous system. Leprosy transmission occurs through continuous and close contact of susceptible people with untreated infected people. However, unknown leprosy contact has been reported in leprosy-affected people, and contact with armadillos is a risk factor for leprosy. In the USA, leprosy is considered a zoonosis and this classification has recently been accepted in Brazil. This review presents information regarding the role of wild armadillos as a source of M. leprae for human infections, as well as the pathogenesis of leprosy.


Asunto(s)
Armadillos/microbiología , Reservorios de Enfermedades/microbiología , Lepra/veterinaria , Mycobacterium leprae , Animales , Modelos Animales de Enfermedad , Humanos , Lepra/microbiología , Lepra/transmisión
14.
Rev Saude Publica ; 53: 61, 2019 Aug 01.
Artículo en Inglés, Portugués | MEDLINE | ID: mdl-31390430

RESUMEN

OBJECTIVE: To analyze the temporal trend of leprosy indicators in a hyperendemic state of Brazil, from 2001-2015. METHODS: This is a time-series study of leprosy indicators in the state of Maranhão, Northeastern region of Brazil. The study used data from the Brazilian National System of Reportable Diseases, for the period between 2001 and 2015. The following indicators were evaluated: (i) detection coefficient in the general population; (ii) detection coefficient in people under 15 years old; (iii) rate of cases with grade 2 physical disability in the diagnosis; (iv) rate of examined contacts, and (v) proportion of healing . The Prais-Winsten regression model was used for trend analysis. Analyses were performed for the state and by each health region. RESULTS: 77,697 leprosy cases were analyzed in the general population and 7,599 in individuals under 15 years old. The detection coefficient in the general population ranged from 80.7/100 thousand inhabitants in 2001 to 51.2/100 thousand inhabitants in 2015. The coefficient in the general population presented a downward trend (annual percentage variation [APV] = -2.98; 95%CI -4.15- -1.79). For the population under 15 years old, the rate was 24.9/100 thousand inhabitants in 2001, and 19.9/100 thousand inhabitants in 2015, with downward trend (APV = -3.07; 95%CI -4.95- -1.15). It was observed upward trend in rate of contacts examined (APV = 2.35; 95%CI 0.58-4.15) and rate of cases with grade 2 disability (APV = 2.19; 95%CI 0.23-4.19). Stationary trend was observed in the proportion of healing (APV = -0.10; 95%CI -0.50-0.30). Regional differences were found in the performance of the indicators. CONCLUSIONS: A downward trend for the detection coefficients in the general population and in individuals under 15 years old was found in Maranhão. Despite this result, the rates are still very high, demanding efforts from all spheres of public administration and health professionals to reduce the burden of the disease in the state.


Asunto(s)
Enfermedades Endémicas/estadística & datos numéricos , Indicadores de Salud , Lepra/epidemiología , Enfermedades Desatendidas/epidemiología , Adolescente , Adulto , Anciano , Brasil/epidemiología , Femenino , Geografía , Humanos , Lepra/diagnóstico , Lepra/prevención & control , Lepra/transmisión , Modelos Lineales , Masculino , Persona de Mediana Edad , Vigilancia de la Población , Factores de Tiempo , Adulto Joven
15.
EBioMedicine ; 47: 301-308, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31422044

RESUMEN

BACKGROUND: Transmission of Mycobacterium leprae, the pathogen causing leprosy, is still persistent. To facilitate timely (prophylactic) treatment and reduce transmission it is vital to both early diagnose leprosy, and identify infected individuals lacking clinical symptoms. However, leprosy-specific biomarkers are limited, particularly for paucibacillary disease. Therefore, our objective was to identify new biomarkers for leprosy and assess their applicability in point-of-care (POC) tests. METHODS: Using multiplex-bead-arrays, 60 host-proteins were measured in a cross-sectional approach in 24-h whole blood assays (WBAs) collected in Bangladesh (79 patients; 54 contacts; 51 endemic controls (EC)). Next, 17 promising biomarkers were validated in WBAs of a separate cohort (55 patients; 27 EC). Finally, in a third cohort (36 patients; 20 EC), five candidate markers detectable in plasma were assessed for application in POC tests. FINDINGS: This study identified three new biomarkers for leprosy (ApoA1, IL-1Ra, S100A12), and confirmed five previously described biomarkers (CCL4, CRP, IL-10, IP-10, αPGL-I IgM). Overnight stimulation in WBAs provided increased specificity for leprosy and was required for IL-10, IL-1Ra and CCL4. The remaining five biomarkers were directly detectable in plasma, hence suitable for rapid POC tests. Indeed, lateral flow assays (LFAs) utilizing this five-marker profile detected both multi- and paucibacillary leprosy patients with variable immune responses. INTERPRETATION: Application of novel host-biomarker profiles to rapid, quantitative LFAs improves leprosy diagnosis and allows POC testing in low-resource settings. This platform can thus aid diagnosis and classification of leprosy and also provides a tool to detect M.leprae infection in large-scale contact screening in the field.


Asunto(s)
Biomarcadores , Interacciones Huésped-Patógeno , Lepra/sangre , Lepra/diagnóstico , Pruebas en el Punto de Atención , Adolescente , Adulto , Biomarcadores/sangre , Niño , Preescolar , Estudios Transversales , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Lactante , Recién Nacido , Lepra/microbiología , Lepra/transmisión , Masculino , Pruebas en el Punto de Atención/normas , Curva ROC , Sensibilidad y Especificidad , Flujo de Trabajo , Adulto Joven
16.
Fontilles, Rev. leprol ; 32(2): 87-104, mayo-ago. 2019. tab
Artículo en Español | IBECS | ID: ibc-187212

RESUMEN

Se realizó una investigación observacional descriptiva prospectiva con el objetivo de determinar la eficacia del uso de la rifampicina como tratamiento profiláctico en los contactos de primer orden de los casos de lepra en el municipio Camagüey, durante los años 2000 al 2010. Predomino el grupo de 40 a 49 años, sin diferencias significativas en cuanto al sexo. En más de la mitad de los contactos el per cápita familiar fue malo y tenían hacinamiento. La madre resultó ser la fuente de infección más probable, con más de 10 años de convivencia con los contactos en la mayoría de los casos. Un mínimo por ciento de los contactos desarrolló lepra, con serología UMELISA HANSEN reactiva y examen dermato-neurológico con lesiones sugestivas de la enfermedad y uno solo con baciloscopia positiva. Los enfermos presentaron lepra paucibacilar, dentro de esta, la indeterminada. Se concluyó que la quimioprofilaxis con rifampicina en dosis única no fue totalmente efectiva


A prospective, descriptive, observational investigation was carried out with the aim of determining the effectiveness of the use of the rifampicin as a preventive treatment in household contacts of leprosy in Camagüey city, from 2000 to 2010. The majority of the contacts were in the age group from 40 to 49 years, without significant gender differences. In more than half of the contacts, the family income rate was poor and they lived in harsh conditions. In the majority of cases, the mother turned out to be the source of infection. A very small percent of the contacts developed leprosy, with positive ELISA serology and dermal - neurological examination with suggestive lesions of the illness and only one case with positive skin smear. The affected individuals presented indeterminate leprosy a form of paucibacillary leprosy. The study concluded that Chemoprophylaxis with only one dose of rifampicin was not totally effective


Asunto(s)
Humanos , Masculino , Femenino , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Trazado de Contacto/estadística & datos numéricos , Leprostáticos/uso terapéutico , Rifampin/uso terapéutico , Lepra/transmisión , Factores Socioeconómicos , Profilaxis Posexposición , Estudios Prospectivos , Lepra/prevención & control , Cuba
17.
Rev. pesqui. cuid. fundam. (Online) ; 11(4): 873-879, jul.-set. 2019. tab, graf
Artículo en Inglés, Portugués | LILACS, BDENF - Enfermería | ID: biblio-1005618

RESUMEN

Objetivo: Avaliar a situação dos contatos intradomiciliares dos casos de hanseníase notificados no ano de 2012 em São Luís/Maranhão. Métodos: Estudo quantitativo-descritivo-transversal, com coleta de dados utilizando-se instrumento estruturado. Resultados: A maioria dos contatos intradomiciliares eram mulheres (51,87%), idade entre 0 e 20 anos (40,29%), parentesco consanguíneo de 1º grau (54,92%), forma dimorfa (59,78%) e multibacilares (75,53%). Do total, 1880 (67,96%) não realizaram o exame dermatoneurológico. Entre os examinados, houve maior frequência no distrito Bequimão (28,48%), no qual 59,82% eram mulheres, idade entre 0 a 20 anos (44,77%). Ao exame, 91,27% apresentou-se normal. Dentre os suspeitos, 36,73% tinham hanseníase, 58,21% possuíam cicatriz da 1ª dose da BCG e 59,98% foram encaminhados a vacinação. A prevalência da doença entre os contatos foi de 1,62%. As ações da vigilância de contatos classificaram-se como precárias em São Luís. Conclusão: A maioria dos contatos registrados não foi examinada, evidenciando necessidade de fortificação das ações da vigilância no município


Objective: To evaluate the situation of in-house contacts of the cases of leprosy reported in 2012 in São Luis, Maranhão. Methods: Quantitative cross-sectional descriptive study, with data collection using a structured instrument. Results: The majority of in-house contacts were women (51.87%), from 0 to 20 years of age (40.29%), first-degree kinship (54.92%), dimorphic shape (59.78) and multibacillary (75.53%). In total, 1880 (67.96%) did not take the dermato-neurological exam. Among those tested, there was a greater frequency in the Bequimão district (2.48%), 59.82% were women, from 0 to 20 years of age (44.77%). On the exam, 91.27% were normal. Among those suspected of carrying the disease, 36.73% had leprosy, 58.21% had scars from the first dose of BCG and 59.98% were sent to receive vaccination. The prevalence of the disease among the contacts was 1.62%. The actions of contact monitoring were classified as precarious in São Luis. Conclusion: The majority of registered contacts were not examined, highlighting the need for strengthening of monitoring efforts in the city


Objetivo: Evaluar la situación de los contactos intradomiciliares de los casos de hanseniasis notificados en el año 2012 en São Luis - MA. Métodos: Estudio cuantitativo-descriptivo-transversal, con recolección de datos utilizando instrumento estructurado. Resultados: La mayoría de los contactos intradomiciliares eran mujeres (51,87%), edad entre 0 y 20 años (40,29%), parentesco consanguíneo de primer grado (54,92%), forma dimorfa (59,78%), multibacilares (75,53%). Del total, 1880 (67,96%) no realizaron el examen dermatoneurológico. Entre los examinados, hubo mayor frecuencia en el distrito de Bequimão (28,48%), el 59,82% eran mujeres, entre 0 a 20 años (44,77%). En el examen, el 91,27% se presentó normal. Entre los sospechosos, el 36,73% tenían hanseniasis, el 58,21% tenía cicatriz de la 1ª dosis de BCG y el 59,98% fueron encaminados a la vacunación. La prevalencia de la enfermedad entre los contactos fue del 1,62%. Las acciones de la vigilancia de contactos se clasificaron como precarias en San Luis. Conclusión: La mayoría de los contactos registrados no fueron examinados, evidenciando necesidad de fortificación de las acciones de la vigilancia en el municipio


Asunto(s)
Humanos , Masculino , Femenino , Recién Nacido , Lactante , Preescolar , Niño , Adolescente , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Notificación de Enfermedades/estadística & datos numéricos , Lepra/transmisión , Lepra/epidemiología , Contaminación Ambiental/prevención & control , Registros Electrónicos de Salud/estadística & datos numéricos , Monitoreo Epidemiológico
18.
BMC Infect Dis ; 19(1): 520, 2019 Jun 13.
Artículo en Inglés | MEDLINE | ID: mdl-31196008

RESUMEN

BACKGROUND: Leprosy is is still considered a public health issue and in Colombia 7-10% of new cases are found in children, indicating both active transmission and social inequality. We hypothesized that circulating antibodies against Natural Octyl Disaccharide-Leprosy IDRI Diagnostic (NDO-LID) (a combination of Mycobacterium leprae antigens) could reveal the social and environmental aspects associated with higher frequencies of M. leprae infection among children and adolescents in Colombia. METHODS: An observational cross-sectional study was conducted involving sampling from 82 children and adolescents (younger than 18 years of age) who had household contact with index leprosy patients diagnosed in the last 5 years. Data were analyzed through bivariate analysis made by applying a Pearson x2 test for qualitative variables, while quantitative variables, depending on their distribution, were analyzed using either a Student's t-test or Mann-Whitney U test. Multivariate analysis was performed using a multiple regression and binomial logistic approach. RESULTS: A bivariate analysis demonstrated that antibody titers against NDO-LID were significantly greater in children and adolescents with a low socioeconomic status that had: lived in vulnerable areas of the UAChR shared region; eaten armadillo meat; exposure of over 10 years to an index case and; not received BCG immunization. Moreover, a multivariate analysis showed that residing in the UAChR region has a strong association with a greater possibility of M. leprae infection. CONCLUSIONS: M. leprae transmission persists among young Colombians, and this is associated with social and environmental conditions. An intensification of efforts to identify new leprosy cases in vulnerable and forgotten populations where M. leprae transmission continues therefore appears necessary.


Asunto(s)
Lepra/diagnóstico , Mycobacterium leprae/aislamiento & purificación , Adolescente , Animales , Anticuerpos Antibacterianos/sangre , Armadillos , Vacuna BCG/inmunología , Niño , Preescolar , Colombia/epidemiología , Estudios Transversales , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Lactante , Lepra/epidemiología , Lepra/transmisión , Modelos Logísticos , Masculino , Carne/análisis , Carne/microbiología , Mycobacterium leprae/inmunología , Clase Social , Estadísticas no Paramétricas
20.
Immunobiology ; 224(4): 518-525, 2019 07.
Artículo en Inglés | MEDLINE | ID: mdl-31109749

RESUMEN

Hansen's disease (or leprosy) still persists as a serious public health issue. Its diagnosis is based primarily on the detection of clinical signs that are characteristic of the disease. Studies have pointed to the selection of a set of serological and cellular biomarkers of subclinical infection that result in an efficient diagnosis. The aim of this study was compare index cases and their household contacts to identify differentially expressed biomarkers of immune response in leprosy that could provide reliable evidence of subclinical infection in household contacts. The study population consisted of index cases with multibacillary form (IC, n = 13) and their household contacts (HC, n = 14). Serum cytokines and chemokines were quantified using the cytometric beads array (CBA) system. The humoral response was assessed by ELISA test. Flow cytometry was used to characterize the cellular immune response. Monocyte and CD4 + T lymphocytes frequency was significantly higher in IC. Both CD4+ and CD8 + T lymphocytes had a reduced CD25 expression in HC. The immunoglobulin (Ig)M profile anti- NDO-HSA, LID-1, and NDOLID antigens was significantly higher in IC. This study points to the monocyte and CD4+ lymphocyte frequency, as well as specific IgM profile, as predictors of subclinical infection in the household contacts.


Asunto(s)
Biomarcadores , Familia , Lepra/diagnóstico , Lepra/inmunología , Adolescente , Adulto , Anciano , Niño , Preescolar , Estudios Transversales , Citocinas/sangre , Femenino , Humanos , Inmunoglobulina M/inmunología , Lactante , Lepra/microbiología , Lepra/transmisión , Leucocitos/inmunología , Leucocitos/metabolismo , Masculino , Persona de Mediana Edad , Mycobacterium leprae/inmunología , Índice de Severidad de la Enfermedad
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