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1.
Trials ; 19(1): 244, 2018 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-29685164

RESUMEN

BACKGROUND: The annual new-case detection rate for leprosy, while generally stable over the last decade, shows that transmission rates have remained stagnant despite the successful worldwide administration of multidrug therapy since the 1980s. As such, novel control strategies are urgently needed. Focusing on managing leprosy patient contacts, the most susceptible to contracting the disease, has been seen as a potential strategy in limiting the spread of leprosy as shown by a number of recent epidemiological studies. Immunoprophylaxis with Bacillus Calmette-Guérin (BCG) has been seen as an effective preventive measure due to its ability to stimulate the development of cellular immunity which is essential in controlling the disease, especially in its multibacillary (MB) forms. The association of immunoprophylaxis with chemoprophylaxis in a single dose of rifampicin has been shown to be a promising preventive strategy, although a variety of studies have found instances of early case detection just a few months after BCG vaccination. METHODS/DESIGN: The present study is a phase IV chemoprophylactic clinical trial consisting of administration of a single dose of rifampicin in MB leprosy patient contacts under care at the Souza Araújo Outpatient Clinic/FIOCRUZ as part of a randomized (2:1), double-blind, placebo-controlled study. It is comprised of two groups: 1) rifampicin + BCG; and 2) placebo + BCG. DISCUSSION: The aim is to evaluate whether the use of chemoprophylaxis with a single dose of rifampicin in MB leprosy patient contacts prior to the BCG vaccine would be able to prevent the onset of leprosy in those cases that may occur just a few months after vaccination. Contact subclinical infections (polymerase chain reaction) and the immunological parameters (anti-PGL-1, anti-LID-1, and IFN-γ) will be evaluated and the results will be compared after 12 months of follow-up. TRIAL REGISTRATION: The Brazilian Registry of Clinical Trials (ReBEC), RBR-69QK5P . Retrospectively registered on 1 June 2017.


Asunto(s)
Vacuna BCG/administración & dosificación , Trazado de Contacto , Leprostáticos/administración & dosificación , Lepra Multibacilar/prevención & control , Rifampin/administración & dosificación , Adolescente , Adulto , Anciano , Vacuna BCG/efectos adversos , Brasil , Niño , Preescolar , Ensayos Clínicos Fase IV como Asunto , Método Doble Ciego , Esquema de Medicación , Femenino , Humanos , Lactante , Leprostáticos/efectos adversos , Lepra Multibacilar/inmunología , Lepra Multibacilar/microbiología , Lepra Multibacilar/transmisión , Masculino , Persona de Mediana Edad , Ensayos Clínicos Controlados Aleatorios como Asunto , Rifampin/efectos adversos , Factores de Tiempo , Resultado del Tratamiento , Vacunación , Adulto Joven
2.
J Eur Acad Dermatol Venereol ; 29(7): 1354-61, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-25429820

RESUMEN

BACKGROUND: Studies on the immunology of leprosy are fundamental to the understanding of the various forms of clinical manifestation of the disease. In some diseases, lymphocytes TH17 and one of its key cytokines, interleukin-17 has been shown to be essential in developing an effective immune response. In leprosy, involvement of lymphocyte TH17 and interleukin-17 remains understudied. OBJECTIVES: This study is the first investigation to examine the association between TH17 cells, interleukin-17 and interferon- γ in patients and households contacts of leprosy. METHODS: To document the participation of TH17 cells and interleukin-17 in the immunology of leprosy, to observe the behavior of interferon-γ in relation to interleukin-17 and to verify the differences found between individuals paucibacillary, multibacillary and household contacts, we analyzed samples peripheral blood to identify TH-17 cells, interleukin-17 and IFN-γ; establishing relationships between all the groups. RESULTS: There was a significant difference in the results found in the comparison between the paucibacillary and multibacillary groups of patients (P < 0.001), as well with the household contacts (P < 0.005). The polychemotherapeutic treatment modified the profile of immune response in multibacillary patients compared to what was observed before the start of treatment. CONCLUSION: The principal finding was that TH17 lymphocytes and interleukin-17 actively participating in the immune response of Hansen's disease as well these cells can stimulate the cellular immunity.


Asunto(s)
Inmunidad Celular , Interferón gamma/inmunología , Interleucina-17/inmunología , Leprostáticos/uso terapéutico , Lepra Multibacilar/inmunología , Lepra Paucibacilar/inmunología , Células Th17/inmunología , Adolescente , Adulto , Anciano , Femenino , Humanos , Interferón gamma/metabolismo , Interleucina-17/metabolismo , Lepra Multibacilar/tratamiento farmacológico , Lepra Multibacilar/transmisión , Lepra Paucibacilar/tratamiento farmacológico , Lepra Paucibacilar/transmisión , Masculino , Persona de Mediana Edad , Adulto Joven
3.
Clin Microbiol Infect ; 20(5): 447-52, 2014 May.
Artículo en Inglés | MEDLINE | ID: mdl-24033793

RESUMEN

Leprosy epidemiological studies have been restricted to Mycobacterium leprae DNA detection in nasal and oral mucosa samples with scarce literature on peripheral blood. We present the largest study applying quantitative real-time PCR (qPCR) for the detection of M. leprae DNA in peripheral blood samples of 200 untreated leprosy patients and 826 household contacts, with results associated with clinical and laboratory parameters. To detect M. leprae DNA a TaqMan qPCR assay targeting the M. leprae ML0024 genomic region was performed. The ML0024 qPCR in blood samples detected the presence of bacillus DNA in 22.0% (44/200) of the leprosy patients: 23.2% (16/69) in paucibacillary (PB), and 21.4% (28/131) in multibacillary (MB) patients. Overall positivity among contacts was 1.2% (10/826), with similar percentages regardless of whether the index case was PB or MB. After a follow-up period of 7 years, 26 contacts have developed leprosy. Comparing the results of healthy contacts with those that become ill, ML0024 qPCR positivity at the time of diagnosis of their index case represented an impressive 14.78-fold greater risk for leprosy onset (95% CI 3.6-60.8; p <0.0001). In brief, contacts with positive PCR in blood at diagnosis of index cases are at higher risk of later leprosy onset and this marker might be combined with other prognostic markers for management of contacts, which requires further studies.


Asunto(s)
ADN Bacteriano/sangre , Lepra Multibacilar/sangre , Lepra Multibacilar/transmisión , Lepra Paucibacilar/sangre , Lepra Paucibacilar/transmisión , Mycobacterium leprae/genética , Proteínas Bacterianas/genética , Portador Sano/sangre , Estudios de Seguimiento , Humanos , Lepra Multibacilar/epidemiología , Lepra Paucibacilar/epidemiología , Mycobacterium leprae/aislamiento & purificación , Reacción en Cadena en Tiempo Real de la Polimerasa , Factores de Riesgo
4.
Clin Microbiol Infect ; 20(1): 59-64, 2014 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-23473290

RESUMEN

In leprosy, the nasal mucosa is considered as the principal route of transmission for the bacillus Mycobacterium leprae. The objective of this study was to identify M. leprae in the oral mucosa of 50 untreated leprosy patients, including 21 paucibacillary (PB) and 29 multibacillary (MB) patients, using immunohistochemistry (IHC), with antibodies against bacillus Calmette-Guérin (BCG) and phenolic glycolipid antigen-1 (PGL-1), and polymerase chain reaction (PCR), with MntH-specific primers for M. leprae, and to compare the results. The material was represented by 163 paraffin blocks containing biopsy samples obtained from clinically normal sites (including the tongue, buccal mucosa and soft palate) and visible lesions anywhere in the oral mucosa. All patients and 158 available samples were included for IHC study. Among the 161 available samples for PCR, 110 had viable DNA. There was viable DNA in at least one area of the oral mucosa for 47 patients. M. leprae was detected in 70% and 78% of patients using IHC and PCR, respectively, and in 94% of the patients by at least one of the two diagnostic methods. There were no differences in detection of M. leprae between MB and PB patients. Similar results were obtained using anti-BCG and anti-PGL-1 antibodies, and immunoreactivity occurred predominantly on free-living bacteria on the epithelial surface, with a predilection for the tongue. Conversely, there was no area of predilection according to the PCR results. M. leprae is present in the oral mucosa at a high frequency, implicating this site as a potential means of leprosy transmission.


Asunto(s)
Lepra Multibacilar/microbiología , Lepra Paucibacilar/microbiología , Mucosa Bucal/microbiología , Mycobacterium leprae/aislamiento & purificación , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Proteínas Bacterianas/genética , Proteínas de Transporte de Catión/genética , Estudios Transversales , Femenino , Humanos , Inmunohistoquímica , Lepra Multibacilar/epidemiología , Lepra Multibacilar/transmisión , Lepra Paucibacilar/epidemiología , Lepra Paucibacilar/transmisión , Masculino , Persona de Mediana Edad , Mycobacterium leprae/genética , Mycobacterium leprae/inmunología , Reacción en Cadena de la Polimerasa , Estudios Retrospectivos , Adulto Joven
5.
Int J Dermatol ; 53(4): 462-5, 2014 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-23968315

RESUMEN

OBJECTIVES: Our objective was to study current trends in the occurrence of new cases of leprosy (Hansen's disease [HD]) a decade after significant operational changes in the National Leprosy Elimination Program (NLEP) were enacted by shortening the duration of multi-drug treatment for multibacillary cases of HD to 12 months and stopping post-treatment follow-up. METHODS: The percentages represented by newly diagnosed cases of HD among all new patients attending the dermatology outpatient department (OPD) from April 2008 to March 2011 were calculated from hospital records. Patient age and sex, and type of disease were noted in each case, and annual data were compared. The OPD data were also matched with population data for the catchment area of the hospital (i.e. the South 24-Parganas district). RESULTS: There was a slight annual decline in the percentage of new cases represented by HD, but this was not statistically significant. This trend broadly corroborated changes in the annual new case detection rate in the catchment area of the hospital. In addition, the percentage of HD cases represented by paucibacillary disease was significantly higher than that represented by multibacillary HD (P=0.0072). CONCLUSIONS: To the best of our knowledge, this is the first study of this type to be conducted in eastern India. The present data indicate that significant transmission of HD is ongoing in the community.


Asunto(s)
Leprostáticos/administración & dosificación , Lepra Multibacilar/epidemiología , Lepra Paucibacilar/epidemiología , Femenino , Humanos , Incidencia , India/epidemiología , Lepra Multibacilar/tratamiento farmacológico , Lepra Multibacilar/transmisión , Lepra Paucibacilar/tratamiento farmacológico , Lepra Paucibacilar/transmisión , Masculino , Servicio Ambulatorio en Hospital/estadística & datos numéricos , Estudios Retrospectivos
6.
Infect Genet Evol ; 12(1): 121-6, 2012 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-22101333

RESUMEN

Leprosy is a disease caused by Mycobacterium leprae. Various modes of transmission have been suggested for this disease. Transmission and risk of the infection is perhaps related to presence of the infectious cases and is controlled by environmental factors. Evidence suggests that humidity may favor survival of M. leprae in the environment. Several reports show that non-human sources like 'naturally' infected armadillos or monkeys could act as reservoir for M. leprae. Inanimate objects or fomites like articles used by infectious patients may theoretically spread infection. However, it is only through detailed knowledge of the biodiversity and ecology that the importance of this mode of transmission can be fully assessed. Our study focuses here to decipher the role of environment in the transmission of the disease. Two hundred and seven soil samples were collected from a village in endemic area where active cases also resided at the time of sample collection. Slit skin smears were collected from 13 multibacillary (MB) leprosy patients and 12 household contacts of the patients suspected to be hidden cases. DNA and RNA of M. leprae were extracted and amplified using M. leprae specific primers. Seventy-one soil samples showed presence of M. leprae DNA whereas 16S rRNA could be detected in twenty-eight of these samples. Samples, both from the environment and the patients, exhibited the same genotype when tested by single nucleotide polymorphism (SNP) typing. Genotype of M. leprae found in the soil and the patients residing in the same area could help in understanding the transmission link in leprosy.


Asunto(s)
Lepra Multibacilar/transmisión , Mycobacterium leprae/patogenicidad , Microbiología del Suelo , Técnicas de Tipificación Bacteriana , ADN Bacteriano/genética , ADN Bacteriano/aislamiento & purificación , Ambiente , Genotipo , Humanos , India , Lepra Multibacilar/microbiología , Mycobacterium leprae/clasificación , Mycobacterium leprae/genética , Polimorfismo de Nucleótido Simple , ARN Bacteriano/genética , ARN Bacteriano/aislamiento & purificación , ARN Ribosómico 16S/genética , ARN Ribosómico 16S/aislamiento & purificación , Piel/microbiología , Suelo/análisis
7.
Lepr Rev ; 82(1): 6-16, 2011 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-21644467

RESUMEN

BACKGROUND: Leprosy control and management in China was maintained via a vertical system. Despite substantial achievements in leprosy control in the past decades, leprosy has not been completely eliminated in several endemic areas of Yunnan Province, China. OBJECTIVES: To report the epidemiological trends and management of leprosy in Yuxi, Yunnan Province from 1952 to 2008. DESIGN: Diagnosis, control, and treatment data for 2223 leprosy cases detected from 1952 to 2008 were analysed. RESULTS: Two large-scale house-to-house surveys were launched in 1957-1958 and 1964-1965, and a remarkable number of new cases were identified during these two surveys. The overall prevalence rate of leprosy in the Yuxi region presented a roughly unimodal distribution between 1952 and 2008, with a peak (9.27 per 10000 population) in 1965. This reflects a combination of case detection and duration of treatment. Overall, the age distribution of the patients changed dramatically over the years, and there were only two childhood cases between 1995 and 2008 (both occurring in 1998). Nearly half of the total cases (49.1%) were classified as multibacillary leprosy type. With the introduction and ubiquitous coverage of the WHO multi-drug therapy (MDT) in this area, leprosy elimination was achieved in 1992. In recent years, the majority of cases (> 80%) were detected by passive approaches, and there is an increasing tendency to find multibacillary leprosy patients. CONCLUSIONS: Our results provide an overall profile of our 57-year effort regarding the leprosy control in the Yuxi region. The trend in detection of new cases in recent years suggested that the transmission of leprosy has stopped in the area or, at least, dramatically declined.


Asunto(s)
Control de Enfermedades Transmisibles/organización & administración , Lepra Multibacilar/epidemiología , Lepra Multibacilar/prevención & control , Distribución por Edad , China/epidemiología , Femenino , Encuestas Epidemiológicas , Humanos , Lepra Multibacilar/microbiología , Lepra Multibacilar/transmisión , Masculino , Prevalencia
8.
J Fam Pract ; 58(12): 657-9, 2009 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-19961820

RESUMEN

A 43-year-old man visiting Texas from Hawaii sought care at our dermatology clinic for nonpruritic erythematous plaques on his chest, back, and extremities. The patient reported occasional numbness in his fingers and feet, but denied constitutional symptoms. The patient, who'd had these symptoms for a year, had been previously diagnosed with chronic urticaria and treated with oral antihistamines. He reported that the lesions were never particularly pruritic and he had not responded to previous treatments. An avid outdoorsman, our patient was born and raised in Texas and had been living in Hawaii. His past medical history was significant for severe hand eczema and when asked about medications he was taking, he listed cetirizine, doxepin, and hydroxyzine. On physical examination the patient had multiple pink to red, nonscaly to minimally scaly flat plaques on his forehead, chest, proximal upper extremities, lower back, and distal lower extremities. A 4-mm punch biopsy was taken from a lesion on his lower back and sent for histologic evaluation. The patient's erythrocyte sedimentation rate, rapid plasma reagin, and complete blood count were all within normal limits. What is your diagnosis? How would you treat this patient?


Asunto(s)
Lepra Multibacilar/diagnóstico , Adulto , Animales , Armadillos , Biopsia , Clofazimina/uso terapéutico , Dapsona/uso terapéutico , Diagnóstico Diferencial , Quimioterapia Combinada , Eritema/microbiología , Dermatosis de la Mano/microbiología , Humanos , Leprostáticos/uso terapéutico , Lepra Multibacilar/tratamiento farmacológico , Lepra Multibacilar/transmisión , Masculino , Rifampin/uso terapéutico , Piel/patología , Zoonosis
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