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1.
Clin Infect Dis ; 2019 Nov 16.
Artículo en Inglés | MEDLINE | ID: mdl-31732729

RESUMEN

BACKGROUND: Mycobacterium leprae was thought the exclusive causative agent of leprosy until Mycobacterium lepromatosis was identified in a rare form of leprosy known as diffuse lepromatous leprosy (DLL). METHODS: We isolated M. lepromatosis from a patient with DLL and propagated it in athymic nude mouse footpads. Genomic analysis of this strain (NHDP-385) identified a unique repetitive element, RLPM, upon which a specific real-time quantitative PCR (qPCR) assay was developed. The RLPM assay, and our previously developed RLEP qPCR for M. leprae, were validated as clinical diagnostic assays according to Clinical Laboratory Improvement Amendments guidelines. We tested DNA from archived histological sections, patient specimens from the United States (US), Philippines, and Mexico, and US wild armadillos. RESULTS: The limit of detection for the RLEP and RLPM assays is 30 M. leprae per specimen (0.76 bacilli per reaction; CV%: 0.65-2.44) and 122 M. lepromatosis per specimen (3.05 bacilli per reaction; CV%: 0.84-2.9), respectively. In histological sections (n=10), one lepromatous leprosy (LL), one DLL, and three Lucio reactions contained M. lepromatosis; two LL and two Lucio reactions contained M. leprae; one LL contained both species. M. lepromatosis was detected in 3/218 (1.38%) US biopsies. All Philippines specimens (n=180) were M. lepromatosis negative and M. leprae positive. Conversely, 15/47 (31.91%) Mexican specimens were positive for M. lepromatosis; 19/47 (40.43%) were positive for M. leprae; 2/47 (4.26%) contained both organisms. All armadillos were M. lepromatosis negative. CONCLUSIONS: The RLPM and RLEP assays will aid healthcare providers in clinical diagnosis and surveillance of leprosy.

4.
BMC Infect Dis ; 18(1): 506, 2018 Oct 05.
Artículo en Inglés | MEDLINE | ID: mdl-30290790

RESUMEN

The ongoing transmission of Mycobacterium (M.) leprae reflected in a very slow decline in leprosy incidence, forces us to be innovative and conduct cutting-edge research. Single dose rifampicin (SDR) as post-exposure prophylaxis (PEP) for contacts of leprosy patients, reduces their risk to develop leprosy by 60%. This is a promising new preventive measure that can be integrated into routine leprosy control programmes, as is being demonstrated in the Leprosy Post-Exposure Programme that is currently ongoing in eight countries.The limited (60%) effectiveness of SDR is likely due to the fact that some contacts have a preclinical infection beyond the early stages for which SDR is not sufficient to prevent the development of clinical signs and symptoms of leprosy. An enhanced regimen, more potent against a higher load of leprosy bacteria, would increase the effectiveness of this preventive measure significantly.The Netherlands Leprosy Relief (NLR) is developing a multi-country study aiming to show that breaking the chain of transmission of M. leprae is possible, evidenced by a dramatic reduction in incidence. In this study the assessment of the effectiveness of an enhanced prophylactic regimen for leprosy is an important component. To define the so called PEP++ regimen for this intervention study, NLR convened an Expert Meeting that was attended by clinical leprologists, public health experts, pharmacologists, dermatologists and microbiologists.The Expert Meeting advised on combinations of available drugs, with known efficacy against leprosy, as well as on the duration of the intake, aiming at a risk reduction of 80-90%. To come to a conclusion the Expert Meeting considered the bactericidal, sterilising and bacteriostatic activity of the potential drugs. The criteria used to determine an optimal enhanced regimen were: effectiveness, safety, acceptability, availability, affordability, feasibility and not inducing drug resistance.The Expert Meeting concluded that the enhanced regimen for the PEP++ study should comprise three standard doses of rifampicin 600 mg (weight adjusted when given to children) plus moxifloxacin 400 mg given at four-weekly intervals. For children and for adults with contraindications for moxifloxacin, moxifloxacin should be replaced by clarithromycin 300 mg (weight adjusted).


Asunto(s)
Antibacterianos/uso terapéutico , Lepra/prevención & control , Profilaxis Posexposición/métodos , Claritromicina/uso terapéutico , Fluoroquinolonas/uso terapéutico , Humanos , Lepra/tratamiento farmacológico , Lepra/microbiología , Moxifloxacino , Países Bajos , Rifampin/uso terapéutico
5.
s.l; s.n; 2018. 8 p.
No convencional en Inglés | Sec. Est. Saúde SP, HANSEN, SESSP-ILSLPROD, Sec. Est. Saúde SP, SESSP-ILSLACERVO, Sec. Est. Saúde SP | ID: biblio-1025111

RESUMEN

The ongoing transmission of Mycobacterium (M.) leprae reflected in a very slow decline in leprosy incidence, forces us to be innovative and conduct cutting-edge research. Single dose rifampicin (SDR) as post-exposure prophylaxis (PEP) for contacts of leprosy patients, reduces their risk to develop leprosy by 60%. This is a promising new preventive measure that can be integrated into routine leprosy control programmes, as is being demonstrated in the Leprosy Post-Exposure Programme that is currently ongoing in eight countries.The limited (60%) effectiveness of SDR is likely due to the fact that some contacts have a preclinical infection beyond the early stages for which SDR is not sufficient to prevent the development of clinical signs and symptoms of leprosy. An enhanced regimen, more potent against a higher load of leprosy bacteria, would increase the effectiveness of this preventive measure significantly.The Netherlands Leprosy Relief (NLR) is developing a multi-country study aiming to show that breaking the chain of transmission of M. leprae is possible, evidenced by a dramatic reduction in incidence. In this study the assessment of the effectiveness of an enhanced prophylactic regimen for leprosy is an important component. To define the so called PEP++ regimen for this intervention study, NLR convened an Expert Meeting that was attended by clinical leprologists, public health experts, pharmacologists, dermatologists and microbiologists.The Expert Meeting advised on combinations of available drugs, with known efficacy against leprosy, as well as on the duration of the intake, aiming at a risk reduction of 80-90%. To come to a conclusion the Expert Meeting considered the bactericidal, sterilising and bacteriostatic activity of the potential drugs. The criteria used to determine an optimal enhanced regimen were: effectiveness, safety, acceptability, availability, affordability, feasibility and not inducing drug resistance.The Expert Meeting concluded that the enhanced regimen for the PEP++ study should comprise three standard doses of rifampicin 600 mg (weight adjusted when given to children) plus moxifloxacin 400 mg given at four-weekly intervals. For children and for adults with contraindications for moxifloxacin, moxifloxacin should be replaced by clarithromycin 300 mg (weight adjusted).


Asunto(s)
Profilaxis Posexposición , Lepra/prevención & control , Lepra/terapia , Control de Enfermedades Transmisibles , Lepra/tratamiento farmacológico
6.
PLoS Negl Trop Dis ; 11(6): e0005506, 2017 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-28570560

RESUMEN

BACKGROUND: Real-Time PCR-High Resolution Melting (qPCR-HRM) analysis has been recently described for rapid drug susceptibility testing (DST) of Mycobacterium leprae. The purpose of the current study was to further evaluate the validity, reliability, and accuracy of this assay for M. leprae DST in clinical specimens. METHODOLOGY/PRINCIPAL FINDINGS: The specificity and sensitivity for determining the presence and susceptibility of M. leprae to dapsone based on the folP1 drug resistance determining region (DRDR), rifampin (rpoB DRDR) and ofloxacin (gyrA DRDR) was evaluated using 211 clinical specimens from leprosy patients, including 156 multibacillary (MB) and 55 paucibacillary (PB) cases. When comparing the results of qPCR-HRM DST and PCR/direct DNA sequencing, 100% concordance was obtained. The effects of in-house phenol/chloroform extraction versus column-based DNA purification protocols, and that of storage and fixation protocols of specimens for qPCR-HRM DST, were also evaluated. qPCR-HRM results for all DRDR gene assays (folP1, rpoB, and gyrA) were obtained from both MB (154/156; 98.7%) and PB (35/55; 63.3%) patients. All PCR negative specimens were from patients with low numbers of bacilli enumerated by an M. leprae-specific qPCR. We observed that frozen and formalin-fixed paraffin embedded (FFPE) tissues or archival Fite's stained slides were suitable for HRM analysis. Among 20 mycobacterial and other skin bacterial species tested, only M. lepromatosis, highly related to M. leprae, generated amplicons in the qPCR-HRM DST assay for folP1 and rpoB DRDR targets. Both DNA purification protocols tested were efficient in recovering DNA suitable for HRM analysis. However, 3% of clinical specimens purified using the phenol/chloroform DNA purification protocol gave false drug resistant data. DNA obtained from freshly frozen (n = 172), formalin-fixed paraffin embedded (FFPE) tissues (n = 36) or archival Fite's stained slides (n = 3) were suitable for qPCR-HRM DST analysis. The HRM-based assay was also able to identify mixed infections of susceptible and resistant M. leprae. However, to avoid false positives we recommend that clinical specimens be tested for the presence of the M. leprae using the qPCR-RLEP assay prior to being tested in the qPCR-HRM DST and that all specimens demonstrating drug resistant profiles in this assay be subjected to DNA sequencing. CONCLUSION/SIGNIFICANCE: Taken together these results further demonstrate the utility of qPCR-HRM DST as an inexpensive screening tool for large-scale drug resistance surveillance in leprosy.


Asunto(s)
Farmacorresistencia Bacteriana/genética , Lepra/tratamiento farmacológico , Pruebas de Sensibilidad Microbiana/métodos , Mycobacterium leprae/efectos de los fármacos , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Proteínas Bacterianas/genética , ADN Bacteriano/genética , Dapsona/farmacología , Humanos , Leprostáticos/farmacología , Lepra/microbiología , Mycobacterium leprae/aislamiento & purificación , Ofloxacino/farmacología , Reproducibilidad de los Resultados , Rifampin/farmacología , Sensibilidad y Especificidad , Análisis de Secuencia de ADN , Piel/microbiología , Piel/patología
8.
s.l; s.n; 2017. 18 p. tab, graf.
No convencional en Inglés | Sec. Est. Saúde SP, HANSEN, SESSP-ILSLPROD, Sec. Est. Saúde SP, SESSP-ILSLACERVO, Sec. Est. Saúde SP | ID: biblio-1053286

RESUMEN

BACKGROUND: Real-Time PCR-High Resolution Melting (qPCR-HRM) analysis has been recently described for rapid drug susceptibility testing (DST) of Mycobacterium leprae. The purpose of the current study was to further evaluate the validity, reliability, and accuracy of this assay for M. leprae DST in clinical specimens. METHODOLOGY/PRINCIPAL FINDINGS: The specificity and sensitivity for determining the presence and susceptibility of M. leprae to dapsone based on the folP1 drug resistance determining region (DRDR), rifampin (rpoB DRDR) and ofloxacin (gyrA DRDR) was evaluated using 211 clinical specimens from leprosy patients, including 156 multibacillary (MB) and 55 paucibacillary (PB) cases. When comparing the results of qPCR-HRM DST and PCR/direct DNA sequencing, 100% concordance was obtained. The effects of in-house phenol/chloroform extraction versus column-based DNA purification protocols, and that of storage and fixation protocols of specimens for qPCR-HRM DST, were also evaluated. qPCR-HRM results for all DRDR gene assays (folP1, rpoB, and gyrA) were obtained from both MB (154/156; 98.7%) and PB (35/55; 63.3%) patients. All PCR negative specimens were from patients with low numbers of bacilli enumerated by an M. leprae-specific qPCR. We observed that frozen and formalin-fixed paraffin embedded (FFPE) tissues or archival Fite's stained slides were suitable for HRM analysis. Among 20 mycobacterial and other skin bacterial species tested, only M. lepromatosis, highly related to M. leprae, generated amplicons in the qPCR-HRM DST assay for folP1 and rpoB DRDR targets. Both DNA purification protocols tested were efficient in recovering DNA suitable for HRM analysis. However, 3% of clinical specimens purified using the phenol/chloroform DNA purification protocol gave false drug resistant data. DNA obtained from freshly frozen (n = 172), formalin-fixed paraffin embedded (FFPE) tissues (n = 36) or archival Fite's stained slides (n = 3) were suitable for qPCR-HRM DST analysis. The HRM-based assay was also able to identify mixed infections of susceptible and resistant M. leprae. However, to avoid false positives we recommend that clinical specimens be tested for the presence of the M. leprae using the qPCR-RLEP assay prior to being tested in the qPCR-HRM DST and that all specimens demonstrating drug resistant profiles in this assay be subjected to DNA sequencing. CONCLUSION/SIGNIFICANCE: Taken together these results further demonstrate the utility of qPCR-HRM DST as an inexpensive screening tool for large-scale drug resistance surveillance in leprosy.


Asunto(s)
Humanos , Rifampin/farmacología , Piel/microbiología , Proteínas Bacterianas/genética , ADN Bacteriano/genética , Ofloxacino/farmacología , Pruebas de Sensibilidad Microbiana/métodos , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Análisis de Secuencia de ADN , Farmacorresistencia Bacteriana/genética , Dapsona/farmacología , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Leprostáticos/farmacología , Lepra/microbiología , Lepra/tratamiento farmacológico , Mycobacterium leprae/aislamiento & purificación , Mycobacterium leprae/efectos de los fármacos
9.
Am J Trop Med Hyg ; 95(3): 500-501, 2016 09 07.
Artículo en Inglés | MEDLINE | ID: mdl-27430540
10.
Emerg Infect Dis ; 21(12): 2127-34, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26583204

RESUMEN

Nine-banded armadillos (Dasypus novemcinctus) are naturally infected with Mycobacterium leprae and have been implicated in zoonotic transmission of leprosy. Early studies found this disease mainly in Texas and Louisiana, but armadillos in the southeastern United States appeared to be free of infection. We screened 645 armadillos from 8 locations in the southeastern United States not known to harbor enzootic leprosy for M. leprae DNA and antibodies. We found M. leprae-infected armadillos at each location, and 106 (16.4%) animals had serologic/PCR evidence of infection. Using single-nucleotide polymorphism variable number tandem repeat genotyping/genome sequencing, we detected M. leprae genotype 3I-2-v1 among 35 armadillos. Seven armadillos harbored a newly identified genotype (3I-2-v15). In comparison, 52 human patients from the same region were infected with 31 M. leprae types. However, 42.3% (22/52) of patients were infected with 1 of the 2 M. leprae genotype strains associated with armadillos. The geographic range and complexity of zoonotic leprosy is expanding.


Asunto(s)
Mycobacterium leprae/patogenicidad , Zoonosis/epidemiología , Animales , Armadillos , Reservorios de Enfermedades/microbiología , Humanos , Lepra/microbiología , Lepra/transmisión , Louisiana/epidemiología , Mycobacterium leprae/genética , Texas/epidemiología
11.
Dermatol Clin ; 33(3): 541-62, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-26143431

RESUMEN

Leprosy and tuberculosis are chronic mycobacterial infections that elicit granulomatous inflammation. Both infections are curable, but granulomatous injury to cutaneous structures, including cutaneous nerves in leprosy, may cause permanent damage. Both diseases are major global concerns: tuberculosis for its high prevalence and mortality, and leprosy for its persistent global presence and high rate of neuropathic disability. Cutaneous manifestations of both leprosy and tuberculosis are frequently subtle and challenging in dermatologic practice and often require a careful travel and social history and a high index of suspicion.


Asunto(s)
Lepra Lepromatosa/diagnóstico , Lepra Tuberculoide/diagnóstico , Lupus Vulgar/diagnóstico , Piel/patología , Antituberculosos/uso terapéutico , Humanos , Leprostáticos/uso terapéutico , Lepra/diagnóstico , Lepra/tratamiento farmacológico , Lepra Lepromatosa/tratamiento farmacológico , Lepra Tuberculoide/tratamiento farmacológico , Lupus Vulgar/tratamiento farmacológico , Tuberculosis Cutánea/diagnóstico , Tuberculosis Cutánea/tratamiento farmacológico , Tuberculosis Miliar/diagnóstico , Tuberculosis Miliar/tratamiento farmacológico
12.
Clin Dermatol ; 33(1): 46-54, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25432810

RESUMEN

All patients with leprosy have some degree of nerve involvement. Perineural inflammation is the histopathologic hallmark of leprosy, and this localization may reflect a vascular route of entry of Mycobacterium leprae into nerves. Once inside nerves, M. leprae are ingested by Schwann cells, with a wide array of consequences. Axonal atrophy may occur early in this process; ultimately, affected nerves undergo segmental demyelination. Knowledge of the mechanisms of nerve injury in leprosy has been greatly limited by the minimal opportunities to study affected nerves in man. The nine-banded armadillo provides the only animal model of the pathogenesis of M. leprae infection. New tools available for this model enable the study and correlation of events occurring in epidermal nerve fibers, dermal nerves, and nerve trunks, including neurophysiologic parameters, bacterial load, and changes in gene transcription in both neural and inflammatory cells. The armadillo model is likely to enhance understanding of the mechanisms of nerve injury in leprosy and offers a means of testing proposed interventions.


Asunto(s)
Lepra/complicaciones , Mycobacterium leprae/aislamiento & purificación , Neuritis/microbiología , Enfermedades del Sistema Nervioso Periférico/microbiología , Células de Schwann/microbiología , Animales , Armadillos , Atrofia/epidemiología , Atrofia/patología , Axones/patología , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Lepra/microbiología , Masculino , Ratones , Neuritis/fisiopatología , Enfermedades del Sistema Nervioso Periférico/etiología , Enfermedades del Sistema Nervioso Periférico/fisiopatología , Medición de Riesgo , Células de Schwann/patología
13.
Am J Trop Med Hyg ; 92(1): 108-14, 2015 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-25448239

RESUMEN

The objective of this study was to ascertain risk factors for complications (reactions or neuritis) in leprosy patients at the time of diagnosis in three leprosy-endemic countries. Newly diagnosed patients were enrolled in Brazil, the Philippines, and Nepal, and risk factors for reactions and neuritis were assessed using a case-control approach: "cases" were patients with these complications, and controls were patients without complications. Of 1,972 patients enrolled in this study, 22% had complications before treatment. Type 1 reaction was diagnosed in 13.7% of patients, neuritis alone in 6.9.%, and type 2 reaction in 1.4%. The frequency of these complications was higher in Nepal, in lepromatous patients, in males, and in adults versus children. Reactions and neuritis were seen in patients at diagnosis, before treatment was started. Reactions were seen in adults and children, even in patients with only a single lesion. Neuritis was often present without other signs of reaction. Reactions and neuritis were more likely to occur in lepromatous patients, and were more likely to be seen in adults than in children.


Asunto(s)
Enfermedades Endémicas , Lepra/epidemiología , Adolescente , Adulto , Brasil/epidemiología , Niño , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Nepal/epidemiología , Filipinas/epidemiología , Factores de Riesgo , Adulto Joven
14.
PLoS Negl Trop Dis ; 8(9): e3149, 2014 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-25210773

RESUMEN

BACKGROUND: Although immunopathology dictates clinical outcome in leprosy, the dynamics of early and chronic infection are poorly defined. In the tuberculoid region of the spectrum, Mycobacterium leprae growth is restricted yet a severe granulomatous lesion can occur. The evolution and maintenance of chronic inflammatory processes like those observed in the leprosy granuloma involve an ongoing network of communications via cytokines. IL-10 has immunosuppressive properties and IL-10 genetic variants have been associated with leprosy development and reactions. METHODOLOGY/PRINCIPAL FINDINGS: The role of IL-10 in resistance and inflammation in leprosy was investigated using Mycobacterium leprae infection of mice deficient in IL-10 (IL-10-/-), as well as mice deficient in both inducible nitric oxide synthase (NOS2-/-) and IL-10 (10NOS2-/-). Although a lack of IL-10 did not affect M. leprae multiplication in the footpads (FP), inflammation increased from C57Bl/6 (B6)

Asunto(s)
Antígenos Bacterianos/inmunología , Linfocitos T CD4-Positivos/inmunología , Interleucina-10/inmunología , Lepra/inmunología , Mycobacterium leprae/inmunología , Óxido Nítrico Sintasa de Tipo II/inmunología , Animales , Modelos Animales de Enfermedad , Femenino , Interleucina-10/genética , Ratones , Ratones Noqueados , Óxido Nítrico Sintasa de Tipo II/genética
15.
J Clin Immunol ; 34(7): 871-90, 2014 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-25073507

RESUMEN

PURPOSE: Coronin-1A deficiency is a recently recognized autosomal recessive primary immunodeficiency caused by mutations in CORO1A (OMIM 605000) that results in T-cell lymphopenia and is classified as T(-)B(+)NK(+)severe combined immunodeficiency (SCID). Only two other CORO1A-kindred are known to date, thus the defining characteristics are not well delineated. We identified a unique CORO1A-kindred. METHODS: We captured a 10-year analysis of the immune-clinical phenotypes in two affected siblings from disease debut of age 7 years. Target-specific genetic studies were pursued but unrevealing. Telomere lengths were also assessed. Whole exome sequencing (WES) uncovered the molecular diagnosis and Western blot validated findings. RESULTS: We found the compound heterozygous CORO1A variants: c.248_249delCT (p.P83RfsX10) and a novel mutation c.1077delC (p.Q360RfsX44) (NM_007074.3) in two affected non-consanguineous siblings that manifested as absent CD4CD45RA(+) (naïve) T and memory B cells, low NK cells and abnormally increased double-negative (DN) ϒδ T-cells. Distinguishing characteristics were late clinical debut with an unusual mucocutaneous syndrome of epidermodysplasia verruciformis-human papilloma virus (EV-HPV), molluscum contagiosum and oral-cutaneous herpetic ulcers; the older female sibling also had a disfiguring granulomatous tuberculoid leprosy. Both had bilateral bronchiectasis and the female died of EBV+ lymphomas at age 16 years. The younger surviving male, without malignancy, had reproducibly very short telomere lengths, not before appreciated in CORO1A mutations. CONCLUSION: We reveal the third CORO1A-mutated kindred, with the immune phenotype of abnormal naïve CD4 and DN T-cells and newfound characteristics of a late/hypomorphic-like SCID of an EV-HPV mucocutaneous syndrome with also B and NK defects and shortened telomeres. Our findings contribute to the elucidation of the CORO1A-SCID-CID spectrum.


Asunto(s)
Linfocitos B/fisiología , Linfocitos T CD4-Positivos/fisiología , Epidermodisplasia Verruciforme/genética , Granuloma/genética , Células Asesinas Naturales/fisiología , Lepra Tuberculoide/genética , Proteínas de Microfilamentos/genética , Molusco Contagioso/genética , Membrana Mucosa/patología , Infecciones por Papillomavirus/genética , Inmunodeficiencia Combinada Grave/genética , Piel/patología , Adolescente , Niño , Análisis Mutacional de ADN , Epidermodisplasia Verruciforme/etiología , Femenino , Predisposición Genética a la Enfermedad , Granuloma/complicaciones , Heterocigoto , Humanos , Memoria Inmunológica/genética , Lepra Tuberculoide/complicaciones , Masculino , Membrana Mucosa/virología , Mutación/genética , Infecciones por Papillomavirus/etiología , Polimorfismo Genético , Inmunodeficiencia Combinada Grave/complicaciones , Hermanos , Piel/virología , Acortamiento del Telómero/genética
16.
ILAR J ; 54(3): 304-14, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24615444

RESUMEN

Leprosy (also known as Hansen's Disease) is a chronic infectious disease caused by Mycobacterium leprae that primarily targets the peripheral nervous system; skin, muscle, and other tissues are also affected. Other than humans, nine-banded armadillos (Dasypus novemcinctus) are the only natural hosts of M. leprae, and they are the only laboratory animals that develop extensive neurological involvement with this bacterium. Infection in the armadillo closely recapitulates many of the structural, physiological, and functional aspects of leprosy seen in humans. Armadillos can be useful models of leprosy for basic scientific investigations into the pathogenesis of leprosy neuropathy and its associated myopathies, as well as for translational research studies in piloting new diagnostic methods or therapeutic interventions. Practical and ethical constraints often limit investigation into human neuropathies, but armadillos are an abundant source of leprotic neurologic fibers. Studies with these animals may provide new insights into the mechanisms involved in leprosy that also might benefit the understanding of other demyelinating neuropathies. Although there is only a limited supply of armadillo-specific reagents, the armadillo whole genomic sequence has been completed, and gene expression studies can be employed. Clinical procedures, such as electrophysiological nerve conduction testing, provide a functional assessment of armadillo nerves. A variety of standard histopathological and immunopathological procedures including Epidermal Nerve Fiber Density (ENFD) analysis, Schwann Cell Density, and analysis for other conserved cellular markers can be used effectively with armadillos and will be briefly reviewed in this text.


Asunto(s)
Armadillos , Modelos Animales de Enfermedad , Lepra/complicaciones , Enfermedades del Sistema Nervioso Periférico/etiología , Enfermedades del Sistema Nervioso Periférico/fisiopatología , Animales , Recuento de Células , Fenómenos Electrofisiológicos , Epidermis/inervación , Regulación de la Expresión Génica/genética , Humanos , Lepra/genética , Células de Schwann/patología
18.
Clin Infect Dis ; 58(1): 72-3, 2014 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-24065328

RESUMEN

Molecular drug susceptibility testing was performed on 39 US patients with leprosy. Of these, 2 had dapsone-resistant Mycobacterium leprae and 1 of these patients also had rifampin-resistant M. leprae. Even though antileprosy drug resistance occurs in this leprosy population, resistance does not appear to be a major problem.


Asunto(s)
Antibacterianos/farmacología , Farmacorresistencia Bacteriana , Lepra/microbiología , Mycobacterium leprae/efectos de los fármacos , ADN Bacteriano/química , ADN Bacteriano/genética , Dapsona/farmacología , Genes Bacterianos , Humanos , Mycobacterium leprae/genética , Mycobacterium leprae/aislamiento & purificación , Reacción en Cadena de la Polimerasa , Rifampin/farmacología , Análisis de Secuencia de ADN , Estados Unidos
20.
Dis Model Mech ; 6(1): 19-24, 2013 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-23223615

RESUMEN

Leprosy (also known as Hansen's disease) is an infectious peripheral neurological disorder caused by Mycobacterium leprae that even today leaves millions of individuals worldwide with life-long disabilities. The specific mechanisms by which this bacterium induces nerve injury remain largely unknown, mainly owing to ethical and practical limitations in obtaining affected human nerve samples. In addition to humans, nine-banded armadillos (Dasypus novemcinctus) are the only other natural host of M. leprae, and they develop a systemically disseminated disease with extensive neurological involvement. M. leprae is an obligate intracellular parasite that cannot be cultivated in vitro. Because of the heavy burdens of bacilli they harbor, nine-banded armadillos have become the organism of choice for propagating large quantities of M. leprae, and they are now advancing as models of leprosy pathogenesis and nerve damage. Although armadillos are exotic laboratory animals, the recently completed whole genome sequence for this animal is enabling researchers to undertake more sophisticated molecular studies and to develop armadillo-specific reagents. These advances will facilitate the use of armadillos in piloting new therapies and diagnostic regimens, and will provide new insights into the oldest known infectious neurodegenerative disorder.


Asunto(s)
Armadillos , Lepra/etiología , Enfermedades Neurodegenerativas/etiología , Crianza de Animales Domésticos , Animales , Armadillos/genética , Armadillos/microbiología , Modelos Animales de Enfermedad , Humanos , Lepra/diagnóstico , Lepra/microbiología , Lepra/terapia , Mycobacterium leprae/patogenicidad , Enfermedades Neurodegenerativas/microbiología , Especificidad de la Especie
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