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1.
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
2.
PLoS Negl Trop Dis ; 14(3): e0008127, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-32203502

RESUMEN

Understanding the prevalence of M. leprae infection in armadillos is important because of evidence from Brazil and other countries of an association between contact with armadillos and the development of Hansen's Disease (leprosy). Our aim was to characterize studies which have investigated natural M. leprae infection in wild armadillos in Brazil, and to quantify and explore variability in the reported prevalence of infection. We conducted a systematic review (PROSPERO CRD42019155277) of publications in MEDLINE, EMBASE, Global Health, Scopus, LILACS, Biblioteca Digital Brasileira de Teses e Dissertações, Catálogo de Teses e Dissertações de CAPES, and Biblioteca Virtual em Saúde up to 10/2019 using Mesh and text search terms (in English, Portuguese, Spanish, and French). The 10 included studies represented a total sample of 302 armadillos comprising 207 (69%) Dasypus novemcinctus, 67 (22%) Euphractus sexcinctus, 16 (5%) Priodontes maximus, 10 (3%) Cabassous unicinctus, and 2 (1%) Cabassous tatouay from 7 different states. Methods used included histopathology (4 studies), PGL-1 and LID-1 antigen detection (4 studies) and examination for clinical signs of disease (4 studies). Eight studies used PCR of which 7 targeted the RLEP repetitive element and 3 tested for inhibitory substances. M. leprae prevalence by PCR ranged from 0% (in 3 studies) to 100% in one study, with a summary estimate of 9.4% (95% CI 0.4% to 73.1%) and a predictive interval of 0-100%. The average prevalence is equivalent to 1 in 10 armadillos in Brazil being infected with M. leprae, but wide variation in sample estimates means that the prevalence in any similar study would be entirely unpredictable. We propose instead that future studies aim to investigate transmission and persistence of M. leprae within and between armadillo populations, meanwhile adopting the precautionary principle to protect human health and an endangered species in Brazil.


Asunto(s)
Armadillos/microbiología , Lepra/epidemiología , Lepra/veterinaria , Mycobacterium leprae/aislamiento & purificación , Animales , Animales Salvajes/microbiología , Brasil/epidemiología , ADN Bacteriano/análisis , Bases de Datos Factuales , Mapeo Geográfico , Mycobacterium leprae/genética , Reacción en Cadena de la Polimerasa , Prevalencia , Secuencias Repetitivas de Ácidos Nucleicos , Zoonosis/epidemiología , Zoonosis/microbiología
3.
BMC Infect Dis ; 20(1): 62, 2020 Jan 20.
Artículo en Inglés | MEDLINE | ID: mdl-31959113

RESUMEN

BACKGROUND: To evaluate the effectiveness and safety of the World Health Organization antibiotic regimen for the treatment of paucibacillary (PB) and multibacillary (MB) leprosy compared to other available regimens. METHODS: We performed a search from 1982 to July 2018 without language restriction. We included randomized controlled trials, quasi-randomized trials, and comparative observational studies (cohorts and case-control studies) that enrolled patients of any age with PB or MB leprosy that were treated with any of the leprosy antibiotic regimens established by the WHO in 1982 and used any other antimicrobial regimen as a controller. Primary efficacy outcomes included: complete clinical cure, clinical improvement of the lesions, relapse rate, treatment failure. Data were pooled using a random effects model to estimate the treatment effects reported as relative risk (RR) with 95% confidence intervals (CI). RESULTS: We found 25 eligible studies, 11 evaluated patients with paucibacillary leprosy, while 13 evaluated patients with MB leprosy and 1 evaluated patients of both groups. Diverse regimen treatments and outcomes were studied. Complete cure at 6 months of multidrug therapy (MDT) in comparison to rifampin-ofloxacin-minocycline (ROM) found RR of 1.06 (95% CI 0.88-1.27) in five studies. Whereas six studies compare the same outcome at different follow up periods between 6 months and 5 years, according to the analysis ROM was not better than MDT (RR of 1.01 (95% CI 0.78-1.31)) in PB leprosy. CONCLUSION: Not better treatment than the implemented by the WHO was found. Diverse outcome and treatment regimens were studied, more statements to standardized the measurements of outcomes are needed.


Asunto(s)
Leprostáticos/uso terapéutico , Lepra Multibacilar/tratamiento farmacológico , Lepra Paucibacilar/tratamiento farmacológico , Minociclina/uso terapéutico , Ofloxacino/uso terapéutico , Rifampin/uso terapéutico , Organización Mundial de la Salud , Adolescente , Adulto , Anciano , Niño , Protocolos Clínicos , Quimioterapia Combinada/efectos adversos , Femenino , Humanos , Leprostáticos/efectos adversos , Masculino , Persona de Mediana Edad , Minociclina/efectos adversos , Mycobacterium leprae/efectos de los fármacos , Mycobacterium leprae/aislamiento & purificación , Enfermedades Desatendidas/tratamiento farmacológico , Ofloxacino/efectos adversos , Recurrencia , Rifampin/efectos adversos , Insuficiencia del Tratamiento , Adulto Joven
4.
BMC Infect Dis ; 19(1): 1013, 2019 Nov 29.
Artículo en Inglés | MEDLINE | ID: mdl-31783808

RESUMEN

BACKGROUND: Leprosy is a chronic granulomatous infection caused by Mycobacterium leprae. It is a polymorphic disease with a wide range of cutaneous and neural manifestations. Ulcer is not a common feature in leprosy patients, except during reactional states, Lucio's phenomenon (LP), or secondary to neuropathies. CASES PRESENTATION: We report eight patients with multibacillary leprosy who presented specific skin ulcers as part of their main leprosy manifestation. Ulcers were mostly present on lower limbs (eight patients), followed by the upper limbs (three patients), and the abdomen (one patient). Mean time from onset of skin ulcers to diagnosis of leprosy was 17.4 months: all patients were either misdiagnosed or had delayed diagnosis, with seven of them presenting grade 2 disability by the time of the diagnosis. Reactional states, LP or neuropathy as potential causes of ulcers were ruled out. Biopsy of the ulcer was available in seven patients: histopathology showed mild to moderate lympho-histiocytic infiltrate with vacuolized histiocytes and intact isolated and grouped acid-fast bacilli. Eosinophils, vasculitis, vasculopathy or signs of chronic venous insufficiency were not observed. Skin lesions improved rapidly after multidrug therapy, without any concomitant specific treatment for ulcers. CONCLUSIONS: This series of cases highlights the importance of recognizing ulcers as a specific cutaneous manifestation of leprosy, allowing diagnosis and treatment of the disease, and therefore avoiding development of disabilities and persistence of the transmission chain of M. leprae.


Asunto(s)
Lepra Multibacilar/diagnóstico , Úlcera Cutánea/diagnóstico , Adolescente , Adulto , Anciano , Errores Diagnósticos , Humanos , Leprostáticos , Lepra Multibacilar/complicaciones , Masculino , Persona de Mediana Edad , Mycobacterium leprae/aislamiento & purificación , Piel/patología , Úlcera Cutánea/complicaciones
5.
PLoS Negl Trop Dis ; 13(12): e0007946, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-31881061

RESUMEN

BACKGROUND: Although leprosy is efficiently treated by multidrug therapy, resistance to first-line (dapsone, rifampin) and second-line (fluoroquinolones) drugs has been described worldwide. However, the characteristics of drug resistance in Southwest China remain unknown. Furthermore, the sensitivity of polymerase chain reaction (PCR)/sequencing for resistance detection is limited, especially for paucibacillary (PB) leprosy patients. The current study aimed to develop a nested PCR/sequencing and TaqMan SNP Genotyping Assay to increase the sensitivity of the method used to detect drug resistance in Mycobacterium leprae and to reveal the nature of M. leprae drug resistance in Southwest China. METHODOLOGY/PRINCIPAL FINDINGS: Seventy-six specimens, including skin biopsy (n = 64), formalin-fixed paraffin-embedded (FFPE) (n = 11) and skin-slit smear (SSS) (n = 1) samples from multibacillary (MB, n = 70) and PB (n = 6) leprosy patients from Southwest China, were included in this study. The presence of mutations in drug resistance-determining regions (DRDRs) of the rpoB, folP1, and gyrA genes, which are associated with rifampicin, dapsone, and quinolone resistance, respectively, was detected by PCR/sequencing, as recommended by the WHO, and the nested PCR and TaqMan SNP Genotyping Assay developed in this study. Mutations in the folP gene were detected in 19 (25.00%) samples, indicating dapsone-resistant M. leprae, with one (1.31%) sample showing mutations in two genes, folP and gyrA, reflecting multidrug-resistant strains to dapsone and ofloxacin. However, no rpoB mutation was detected. Compared with PCR/sequencing, nested PCR increased the sensitivity of detecting rpoB (from 51.39% to 78.94% for leprosy patients and from 0.00% to 50.00% for PB), gyrA (from 75.00% to 80.26% for leprosy patients and from 50.00% to 66.67% for PB), and folP1 (from 5.26% to 84.21% for leprosy patients and from 0.00% to 66.67% for PB). Moreover, the TaqMan SNP Genotyping Assay showed greater sensitivity for folP1 detection (from 5.26% to 78.94-86.84% for leprosy patients and from 0.00% to 33.33%-83.33% for PB patients) than the PCR/sequencing method. In addition, the latter method was able to more easily distinguish heterozygous genotypes and mutant homozygous genotypes from homozygous genotypes. CONCLUSIONS/SIGNIFICANCE: Nested PCR/sequencing and the TaqMan SNP Genotyping Assay are rapid and highly sensitive methods for detecting drug resistance in leprosy cases. The current study revealed that diamino-diphenylsulfone (DDS; also known as dapsone) resistance in M. leprae, as indicated by folP1 gene detection, is still the most concerning form of drug resistance in leprosy patients from Southwest China.


Asunto(s)
Farmacorresistencia Bacteriana , Técnicas de Genotipaje/métodos , Lepra/microbiología , Pruebas de Sensibilidad Microbiana/métodos , Mycobacterium leprae/efectos de los fármacos , Mycobacterium leprae/genética , Reacción en Cadena de la Polimerasa/métodos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , China , Femenino , Genes Bacterianos , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Mycobacterium leprae/aislamiento & purificación , Sensibilidad y Especificidad , Análisis de Secuencia de ADN/métodos , Adulto Joven
6.
Emerg Microbes Infect ; 8(1): 1479-1489, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31621517

RESUMEN

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


Asunto(s)
Farmacorresistencia Bacteriana , Leprostáticos/farmacología , Lepra/microbiología , Mycobacterium leprae/efectos de los fármacos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , China/epidemiología , Femenino , Humanos , Lepra/epidemiología , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Mutación , Mycobacterium leprae/clasificación , Mycobacterium leprae/genética , Mycobacterium leprae/aislamiento & purificación , Filogenia , Adulto Joven
7.
PLoS Negl Trop Dis ; 13(10): e0007731, 2019 10.
Artículo en Inglés | MEDLINE | ID: mdl-31577795

RESUMEN

BACKGROUND: Detection and pathology analysis of Mycobacterium leprae using skin biopsy tissues are essential for leprosy diagnosis and monitoring response to treatment. Although formalin fixation of patient tissues may not be ideal for molecular studies, biopsy samples are the most accessible material from suspected cases. Therefore, clinical molecular laboratories must be able to utilize formalin-fixed, paraffin-embedded (FFPE) material. OBJECTIVE: To determine the best molecular method for diagnosing and monitoring leprosy in FFPE specimens, we developed a single-tube nested PCR (STNPCR) (131 bp) and SYBRGreen PCR (101 bp) assay using primers for the M. leprae-specific repetitive element (RLEP) gene and evaluated the results compared to those using previously established RLEP primers (372 bp). METHODS: FFPE biopsy samples obtained from 145 leprosy patients (during or after multidrug therapy (MDT)) and patients with 29 other confounding dermatoses were examined by the bacteria index (BI) and by simple PCR, STNPCR, and SYBRGreen PCR using primers amplifying a 372-bp, 131-bp or 101-bp fragment of RLEP, respectively. RESULTS: In leprosy patients receiving MDT, STNPCR showed a highest specificity of 100% and a positive predictive value (PPV) of 100%. For multibacillary (MB), paucibacillary (PB) and all leprosy patients, the highest sensitivities were 91.42%, 39.13%, and 67.92%, negative predictive values (NPVs) were 8.57%, 60.36%, and 32.07%, and the highest accuracies were 93.93%, 62.67%, and 74.81%, respectively, higher than the results of SYBRGreen PCR and simple PCR. For post-MDT leprosy patients, SYBRGreen PCR showed the highest sensitivity of 50.0%, highest specificity of 100%, a PPV of 100%, an NPV of 100% and the highest accuracy of 83.72% for MB patients, which were higher than those of STNPCR and simple PCR. STNPCR showed the highest sensitivity of 26.66% and 34.48%, highest specificity of 100% and 100%, a PPV of 100% and 100%, NPV of 72.50% and 60.21%, and highest accuracy of 75.00% and 67.24% for PB and leprosy patients, respectively, higher than those of SYBRGreen PCR and simple PCR. CONCLUSIONS: These findings suggest that STNPCR or SYBRGreen PCR (131-bp and 101-bp fragment amplification, respectively) for RLEP using FFPE specimens performs better as a diagnostic test and for monitoring response to MDT than does simple PCR based on 372-bp fragment amplification. Additionally, STNPCR showed increased sensitivity for PB diagnosis using FFPE specimens, which can be transferred remotely or retrieved from previous leprosy patients.


Asunto(s)
Formaldehído , Lepra/diagnóstico , Mycobacterium leprae/aislamiento & purificación , Adhesión en Parafina/métodos , Reacción en Cadena de la Polimerasa/métodos , Biopsia/métodos , China , Cartilla de ADN , ADN Bacteriano/genética , Quimioterapia Combinada , Humanos , Leprostáticos/uso terapéutico , Lepra/tratamiento farmacológico , Mycobacterium leprae/genética , Secuencias Repetitivas de Ácidos Nucleicos/genética , Sensibilidad y Especificidad , Piel/microbiología
8.
Biosens Bioelectron ; 145: 111698, 2019 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-31539652

RESUMEN

Mycobacterium leprae causes endemic disease leprosy which becomes chronic if not treated timely. To expedite this 'timely diagnosis', and that also at an early stage, here an attempt is made to fabricate an epitope-imprinted sensor. A molecularly imprinted polymer nanoparticles modified electrochemical quartz crystal microbalance sensor was developed for sensing of Mycobacterium leprae bacteria through its epitope sequence. Multiple monomers, 3-sulphopropyl methacrylate potassium salt, benzyl methacrylate and 4-aminothiophenol were utilized to imprint this bacterial epitope. Imprinted nanoparticles were electropolymerized on gold coated quartz electrode. The sensor was able to show specific binding towards the blood samples of infected patients, even in the presence of 'matrix' and other plasma proteins such as albumin and globulin. Even other peptide sequences, similar to epitope sequences only with two amino acid mismatches were also unable to show any binding. Sensor withstood analytical tests viz. selectivity, specificity, matrix effect, detection limit (0.161 nM), quantification limit (and 0.536 nM), reproducibility (RSD 2.01%). Hence a diagnostic tool for bacterium causing leprosy is successfully fabricated in a facile manner which will broaden the clinical access and efficient population screening can be made feasible.


Asunto(s)
Técnicas Biosensibles , Lepra/diagnóstico , Mycobacterium leprae/aislamiento & purificación , Tecnicas de Microbalanza del Cristal de Cuarzo , Epítopos/química , Epítopos/inmunología , Oro/química , Humanos , Lepra/microbiología , Impresión Molecular , Mycobacterium leprae/inmunología , Mycobacterium leprae/patogenicidad , Nanopartículas/química , Polímeros/química
9.
Biomedica ; 39(Supl. 2): 26-31, 2019 08 01.
Artículo en Inglés, Español | MEDLINE | ID: mdl-31529831

RESUMEN

Patients with lepromatous leprosy that have received treatment for many years usually get follow up biopsies for persistent skin lesions or positive bacilloscopy even if the values are lower than in the initial bacilloscopy. We report the case of a 48-year old woman with long-standing lepromatous leprosy of 15 years of evolution, with a bacterial index of 4 in the direct smear and the initial skin biopsy. The patient was treated with multidrug therapy for 32 months although the treatment recommended by the World Health Organization (WHO) is only for 12 months. A skin biopsy was taken to determine if there was an active disease. We observed a diffuse dermal inflammation with numerous foreign body giant cells and vacuolated macrophages (Virchow´s cells). These cells contained granular acid-fast material that was also positive with immunohistochemistry for BCG. There were fragmented bacilli and the BI was 2. These cells were also strongly positive for CD68. The biopsy was interpreted as a residual form of lepromatous leprosy that did not require further multidrug therapy. We have observed similar histological profiles in several cases. The lack of clinical data makes it a histological challenge. The accumulation of lipids in these giant cells is due to bacillary destruction and fusion of vacuolated macrophages. We discuss here the role of bacillary and host lipids in the pathogenesis of lepromatous leprosy. We concluded that there was no need to extend the 12-month multidrug therapy recommended by WHO.


Asunto(s)
Células Espumosas/patología , Células Gigantes de Cuerpo Extraño/patología , Lepra Lepromatosa/patología , Piel/patología , Antígenos CD/análisis , Antígenos de Diferenciación Mielomonocítica/análisis , Biopsia , Pared Celular/química , Quimioterapia Combinada , Femenino , Células Espumosas/química , Células Espumosas/microbiología , Células Gigantes de Cuerpo Extraño/química , Células Gigantes de Cuerpo Extraño/microbiología , Interacciones Huésped-Patógeno , Humanos , Leprostáticos/uso terapéutico , Lepra Lepromatosa/tratamiento farmacológico , Lípidos/análisis , Persona de Mediana Edad , Mycobacterium leprae/química , Mycobacterium leprae/aislamiento & purificación , Piel/microbiología , Vacuolas
10.
Biosens Bioelectron ; 143: 111625, 2019 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-31476595

RESUMEN

The first serum diagnosis of leprosy based on the detection of antibodies of patients using a recombinant mimetic peptide (PGL1M3R) as recognition element and exploiting a photoelectrochemical sensor is presented in this work. The photoeletrochemical platform consists of cadmium sulphide and nickel hydroxide electrodeposited on fluorine-doped tin oxide coated glass slide (CdS/Ni(OH)2/FTO). The optical band gap and flat band potential of the photoelectroactive materials were evaluated by UV-Vis spectroscopy and electrochemical impedance spectroscopy. The spatial photoelectrochemical response of the platform was evaluated by Scanning Electrochemical Microscopy and the morphology of the films was investigated by Scanning Electron Microscopy (SEM). The photoelectrochemical response of the CdS/Ni(OH)2/FTO platform was optimized by evaluating the effects of the kind, concentration, and pH of the buffer. Furthermore, the applied potential to the CdS/Ni(OH)2/FTO platform was also investigated. The CdS/Ni(OH)2/FTO photoelectrochemical platform was modified with a synthetic peptide by using glutaraldehyde as cross-linking reagent and chitosan (CS) for the covalent coupling of the peptide to the photoelectrochemical platform (PGL1M3R/CdS/Ni(OH)2/FTO). The photoelectrochemical immunosensor is able to distinguishing between positive and negative leprosy human sera samples diluted from 1:640 up to 1:10240. Furthermore, to test the specificity of the sensor, samples from tuberculosis and leishmaniasis patients were analyzed using the proposed photoelectrochemical immunosensor.


Asunto(s)
Antígenos Bacterianos/aislamiento & purificación , Técnicas Biosensibles , Lepra/diagnóstico , Mycobacterium leprae/aislamiento & purificación , Biomimética , Humanos , Lepra/microbiología , Mycobacterium leprae/patogenicidad , Proteínas Recombinantes/química
11.
BMC Infect Dis ; 19(1): 753, 2019 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-31462296

RESUMEN

BACKGROUND: Leprosy continues to be a health problem in endemic areas. More than 200,000 new cases of leprosy per year suggest that transmission of the disease is still ongoing, presumably as airborne infection through nasal droplets. Late diagnosis supports continued transmission and increases the individual risk for functional disabilities. Laboratory tools are considered beneficial to facilitate early detection and clinical assessment of cases. The aim of this study was to validate molecular tools allowing detection, quantification and assessment of viability of M. leprae from nasal swab samples which are easy to obtain without the need of any invasive procedures. METHODS: Validation of two real-time PCRs detecting M. leprae DNA (RLEP qPCR) and RNA (16S rRNA RT qPCR) was conducted on "must not detect"/"must detect" samples and 160 pre-treatment nasal swab samples from 20 clinically diagnosed multibacillary (MB) leprosy patients from Togo. RESULTS: Both assays were 100% M. leprae specific and showed analytical sensitivities of three templates each. Out of 20 clinically diagnosed MB leprosy patients, 15 (75.0%) had a positive RLEP qPCR result from nasal swab samples. The 16S rRNA RT qPCR detected viable bacilli in nasal swab samples of ten out of these 15 RLEP positive patients (66.7%). CONCLUSION: The combined RLEP/16S rRNA (RT) qPCR assay provides a sensitive and specific tool to determine the bacterial load and viability of M. leprae from nasal swab samples and is applicable for early diagnosis, monitoring treatment response and investigating the role of nasal carriage of M. leprae in human-to-human transmission through aerosol infection.


Asunto(s)
Lepra/microbiología , Mycobacterium leprae/genética , Cavidad Nasal/microbiología , ARN Ribosómico 16S , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , ADN Bacteriano/genética , Humanos , Lepra/diagnóstico , Lepra Multibacilar/diagnóstico , Lepra Multibacilar/microbiología , Persona de Mediana Edad , Mycobacterium leprae/aislamiento & purificación , Mycobacterium leprae/patogenicidad , ARN Ribosómico 16S/genética , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Togo , Adulto Joven
13.
BMJ Case Rep ; 12(6)2019 Jun 29.
Artículo en Inglés | MEDLINE | ID: mdl-31256049

RESUMEN

Leprosy is a chronic infectious, granulomatous disease caused by the intracellular bacillus Mycobacterium leprae that infects macrophages and Schwann cells. While relatively rare in the USA, there is about 200 new cases of leprosy every year with the majority occurring in the southern parts of the country. It is believed to be linked to the region of the nine-banned armadillo in patients with no significant travel history outside of the country. In this case report, we encountered a 58-year-old Central Florida man that had extensive exposure to armadillos and presented with the typical symptoms of large erythaematous patches, numbness and peripheral nerve hypertrophy. Once diagnosed properly, patients are then reported to the National Hansen's Centre who provides the multidrug therapy for 12-24 months. Due to its rarity and its ability to mimic other more common ailments, leprosy should be included in the differential diagnosis in patients that have significant exposure to armadillos, live in the southern part of the country or have recently travelled to countries that have a high prevalence of leprosy.


Asunto(s)
Armadillos/microbiología , Lepra Lepromatosa/diagnóstico , Mycobacterium leprae/aislamiento & purificación , Animales , Diagnóstico Diferencial , Florida , Humanos , Leprostáticos/uso terapéutico , Lepra Lepromatosa/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Rifampin/uso terapéutico
14.
Microbiol Spectr ; 7(4)2019 07.
Artículo en Inglés | MEDLINE | ID: mdl-31322104

RESUMEN

The mammalian nervous system is invaded by a number of intracellular bacterial pathogens which can establish and progress infection in susceptible individuals. Subsequent clinical manifestation is apparent with the impairment of the functional units of the nervous system, i.e., the neurons and the supporting glial cells that produce myelin sheaths around axons and provide trophic support to axons and neurons. Most of these neurotrophic bacteria display unique features, have coevolved with the functional sophistication of the nervous system cells, and have adapted remarkably to manipulate neural cell functions for their own advantage. Understanding how these bacterial pathogens establish intracellular adaptation by hijacking endogenous pathways in the nervous system, initiating myelin damage and axonal degeneration, and interfering with myelin maintenance provides new knowledge not only for developing strategies to combat neurodegenerative conditions induced by these pathogens but also for gaining novel insights into cellular and molecular pathways that regulate nervous system functions. Since the pathways hijacked by bacterial pathogens may also be associated with other neurodegenerative diseases, it is anticipated that detailing the mechanisms of bacterial manipulation of neural systems may shed light on common mechanisms, particularly of early disease events. This chapter details a classic example of neurodegeneration, that caused by Mycobacterium leprae, which primarily infects glial cells of the peripheral nervous system (Schwann cells), and how it targets and adapts intracellularly by reprogramming Schwann cells to stem cells/progenitor cells. We also discuss implications of this host cell reprogramming by leprosy bacilli as a model in a wider context.


Asunto(s)
Lepra/microbiología , Mycobacterium leprae/fisiología , Sistema Nervioso Periférico/microbiología , Adaptación Fisiológica , Animales , Humanos , Mycobacterium leprae/genética , Mycobacterium leprae/aislamiento & purificación , Células de Schwann/microbiología
15.
Diagn Microbiol Infect Dis ; 95(3): 114855, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31285121

RESUMEN

Early diagnosis of leprosy is important for limiting the severity of disease, which may lead to disabilities and deformities if not treated timely. Multiplex PCR employing more than one gene, specific to target DNA, is more efficient detection tool. In the present study, slit skin scrapings, blood, nasal swabs and saliva from Paucibacillary (PB) and Multibacillary (MB) cases as well as household contacts of PB cases were tested by multiplex PCR using three different gene targets namely RLEP, 16SrRNA and sodA. We found an increase in overall diagnostic positivity for M. leprae DNA detection by M-PCR as compared to individual PCR. In case of nasal swabs using M-PCR the PPV, NPV were 0.5454, 0.8333 respectively. There is remarkable increase in PPV in SSS of PB cases and nasal swabs of HHCs using M-PCR. Conclusively, our finding suggests the utility of M-PCR for early diagnosis and household contact surveillance for leprosy.


Asunto(s)
Técnicas Bacteriológicas/métodos , Pruebas Diagnósticas de Rutina/métodos , Lepra/diagnóstico , Reacción en Cadena de la Polimerasa Multiplex , Mycobacterium leprae/aislamiento & purificación , Vigilancia de la Población/métodos , Diagnóstico Precoz , Humanos , Mycobacterium leprae/genética , Sensibilidad y Especificidad
16.
Emerg Infect Dis ; 25(8): 1604-1607, 2019 08.
Artículo en Inglés | MEDLINE | ID: mdl-31310204

RESUMEN

Whether Mycobacterium leprae transmits from placenta to fetus remains unknown. We describe the case of a pregnant woman with untreated histoid leproma. Although her newborn was healthy, laboratory examination revealed intact M. leprae present in the placenta, suggesting that the placental barrier might prevent vertical dissemination of M. leprae.


Asunto(s)
Lepra/diagnóstico , Lepra/microbiología , Mycobacterium leprae/aislamiento & purificación , Placenta/microbiología , Complicaciones Infecciosas del Embarazo/diagnóstico , Complicaciones Infecciosas del Embarazo/microbiología , Antituberculosos/uso terapéutico , Biopsia , China/epidemiología , Femenino , Humanos , Lepra/epidemiología , Embarazo , Complicaciones Infecciosas del Embarazo/epidemiología , Resultado del Embarazo , Piel/patología , Resultado del Tratamiento , Ultrasonografía
17.
Int J Dermatol ; 58(12): 1415-1422, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31148144

RESUMEN

BACKGROUND: Dermatological diseases have a negative impact on quality of life (QoL), affecting mental and physical health. Leprosy patients usually present with a worse QoL compared with those affected by other conditions. Reactions, neural damage, and pain are some of the consequences that contribute to the lower QoL. However, due to the wide spectrum of the disease, symptoms vary according to leprosy's subtype. This study aimed to compare the QoL between paucibacillary and multibacillary leprosy patients. Individuals were also compared considering the presence of reactions and a correlation between questionnaires was performed. METHODS: A total of 104 patients with leprosy aged 18 years old and over were selected. QoL was assessed by the Brazilian-Portuguese validated versions of the Medical Outcomes Study 36-item short-form health survey (SF-36) and the Dermatology Life Quality Life Index (DLQI). RESULTS: Multibacillary patients showed a more impaired physical function, worse bodily pain, lower score of SF-36, and higher interference of skin on the performance of daily activities when compared to the paucibacillary group. Individuals without reactions presented lower bodily pain and less effect of the skin on clothing choices compared to those with reactions. The SF-36 domains exhibited weak correlations with most DLQI questions, and the linear regression model showed that 32% of changes in QoL were related to the skin aspect. CONCLUSIONS: Multibacillary leprosy patients have a worse QoL when compared to paucibacillary patients. Reactions played a small role in the QoL of our cohort of patients.


Asunto(s)
Lepra Multibacilar/psicología , Lepra Paucibacilar/psicología , Dolor/psicología , Calidad de Vida , Adulto , Brasil , Femenino , Encuestas Epidemiológicas/estadística & datos numéricos , Humanos , Lepra Multibacilar/complicaciones , Lepra Multibacilar/diagnóstico , Lepra Multibacilar/microbiología , Lepra Paucibacilar/complicaciones , Lepra Paucibacilar/diagnóstico , Lepra Paucibacilar/microbiología , Masculino , Persona de Mediana Edad , Mycobacterium leprae/aislamiento & purificación , Dolor/diagnóstico , Dolor/etiología , Dimensión del Dolor , Índice de Severidad de la Enfermedad , Piel/microbiología , Piel/patología
19.
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.
BMC Infect Dis ; 19(1): 455, 2019 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-31117984

RESUMEN

BACKGROUND: Leprosy typically manifests with skin and peripheral nerve involvement. Musculoskeletal complaints are the third most common, and can be the sole presenting manifestation. They range from arthralgia/arthritis in reactional states to full mimics of systemic rheumatic diseases. Remitting Seronegative Symmetrical Synovitis with Pitting Oedema syndrome has only been described once in a patient with already diagnosed Leprosy. CASE REPORT: A 68-year-old male, from an endemic region of familial amyloid polyneuropathy, presented with an inaugural Remitting Seronegative Symmetrical Synovitis with Pitting Oedema like syndrome, more that 20 years after travelling to Leprosy endemic areas. Arthritis would resurface whenever oral prednisone was tapered, so methotrexate was started, controlling the complaints. Only one year later, after the appearance of peripheral neuropathy and skin lesions, it was possible to diagnose Leprosy, through the identification of Mycobacterium leprae bacilli in a peripheral nerve biopsy. CONCLUSION: This report is an example of the heterogeneity of manifestations of Leprosy, namely rheumatic, and the challenge of diagnosing it when typical complaints are absent. It is also a reminder that this disease should be considered whenever a patient with a combination of skin/neurologic/rheumatic complaints has travelled to endemic countries in the past.


Asunto(s)
Edema/diagnóstico , Lepra/etiología , Mycobacterium leprae/aislamiento & purificación , Sinovitis/diagnóstico , Anciano , Antibacterianos , Artritis/tratamiento farmacológico , Artritis/etiología , Edema/etiología , Humanos , Lepra/tratamiento farmacológico , Lepra/microbiología , Masculino , Mycobacterium leprae/patogenicidad , Prednisona/administración & dosificación , Prednisona/uso terapéutico , Piel/microbiología , Piel/patología , Síndrome , Sinovitis/etiología
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