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2.
BMC Infect Dis ; 18(1): 576, 2018 Nov 15.
Article in English | MEDLINE | ID: mdl-30442123

ABSTRACT

BACKGROUND: Since macrophages are one of the major cell types involved in the Mycobacterium leprae immune response, roles of the M1 and M2 macrophage subpopulations have been well defined. However, the role of M4 macrophages in leprosy or other infectious diseases caused by mycobacteria has not yet been clearly characterized. This study aimed to investigate the presence and potential role of M4 macrophages in the immunopathology of leprosy. METHODS: We analyzed the presence of M4 macrophage markers (CD68, MRP8, MMP7, IL-6, and TNF-α) in 33 leprosy skin lesion samples from 18 patients with tuberculoid leprosy and 15 with lepromatous leprosy by immunohistochemistry. RESULTS: The M4 phenotype was more strongly expressed in patients with the lepromatous form of the disease, indicating that this subpopulation is less effective in the elimination of the bacillus and consequently is associated with the evolution to one of the multibacillary clinical forms of infection. CONCLUSION: M4 macrophages are one of the cell types involved in the microbial response to M. leprae and probably are less effective in controlling bacillus replication, contributing to the evolution to the lepromatous form of the disease.


Subject(s)
Leprosy/metabolism , Macrophages/metabolism , Mycobacterium leprae/immunology , Skin Diseases/metabolism , Skin/metabolism , Adult , Biomarkers/metabolism , Brazil , Female , Humans , Immunohistochemistry , Leprosy/immunology , Leprosy/pathology , Leprosy, Lepromatous/immunology , Leprosy, Lepromatous/metabolism , Leprosy, Lepromatous/pathology , Leprosy, Tuberculoid/immunology , Leprosy, Tuberculoid/metabolism , Leprosy, Tuberculoid/pathology , Macrophages/immunology , Macrophages/pathology , Male , Skin/immunology , Skin/pathology , Skin Diseases/immunology , Skin Diseases/microbiology , Skin Diseases/pathology
3.
Microb Pathog ; 118: 277-284, 2018 May.
Article in English | MEDLINE | ID: mdl-29605649

ABSTRACT

Mast cells (MCs) have important immunoregulatory roles in skin inflammation. Annexin A1 (ANXA1) is an endogenous anti-inflammatory protein that can be expressed by mast cells, neutrophils, eosinophils, monocytes, epithelial and T cells. This study investigated MCs heterogeneity and ANXA1 expression in human dermatoses with special emphasis in leprosy. Sixty one skin biopsies from 2 groups were investigated: 40 newly diagnosed untreated leprosy patients (18 reaction-free, 11 type 1 reaction/T1R, 11 type 2 reaction/T2R); 21 patients with other dermatoses. Tryptase/try+ and chymase/chy + phenotypic markers and toluidine blue stained intact/degranulated MC counts/mm2 were evaluated. Try+/chy+ MCs and ANXA1 were identified by streptavidin-biotin-peroxidase immunostaining and density was reported. In leprosy, degranulated MCs outnumbered intact ones regardless of the leprosy form (from tuberculoid/TT to lepromatous/LL), leprosy reactions (reactional/reaction-free) and type of reaction (T1R/T2R). Compared to other dermatoses, leprosy skin lesions showed lower numbers of degranulated and intact MCs. Try+ MCs outnumbered chy+ in leprosy lesions (reaction-free/reactional, particularly in T2R), but not in other dermatoses. Compared to other dermatoses, ANXA1 expression, which is also expressed in mast cells, was higher in the epidermis of leprosy skin lesions, independently of reactional episode. In leprosy, higher MC degranulation and differential expression of try+/chy+ subsets independent of leprosy type and reaction suggest that the Mycobacterium leprae infection itself dictates the inflammatory MCs activation in skin lesions. Higher expression of ANXA1 in leprosy suggests its potential anti-inflammatory role to maintain homeostasis preventing tissue and nerve damage.


Subject(s)
Annexin A1/biosynthesis , Annexin A1/immunology , Anti-Inflammatory Agents/immunology , Anti-Inflammatory Agents/metabolism , Leprosy/immunology , Leprosy/metabolism , Mast Cells/metabolism , Adult , Aged , Aged, 80 and over , Biopsy , Brazil , Chymases/metabolism , Epidermis/immunology , Epidermis/pathology , Female , Humans , Leprosy/pathology , Leprosy, Lepromatous/metabolism , Leprosy, Tuberculoid/metabolism , Male , Mast Cells/pathology , Middle Aged , Mycobacterium leprae/immunology , Mycobacterium leprae/pathogenicity , Skin/pathology , Skin Diseases/metabolism , Skin Diseases/pathology , Tryptases/metabolism , Young Adult
4.
Dis Markers ; 2018: 7067961, 2018.
Article in English | MEDLINE | ID: mdl-30647798

ABSTRACT

Mycobacterium leprae causes leprosy, a dermatoneurological disease which affects the skin and peripheral nerves. One of several cellular structures affected during M. leprae infection is the endoplasmic reticulum (ER). Infection by microorganisms can result in ER stress and lead to the accumulation of unfolded or poorly folded proteins. To restore homeostasis in the cell, the cell induces a series of signaling cascades known as the unfolded protein response called UPR (unfolded protein response). The present work is aimed at investigating the in situ expression of these markers in cutaneous lesions of clinical forms of leprosy and establish possible correlation expression patterns and types of lesion. A total of 43 samples from leprosy patients were analyzed by immunohistochemistry with monoclonal antibodies against GRP78/BiP, PERK, IRE1α, and ATF6. A statistically significant difference between the indeterminate, tuberculoid, and lepromatous clinical forms was detected, with high expression of GRP78/BiP, PERK, IRE1α, and ATF6 in tuberculoid forms (TT) when compared to lepromatous leprosy (LL) and indeterminate (I) leprosy. These results represent the first evidence of ER stress in samples of skin lesions from leprosy patients. We believe that they will provide better understanding of the complex pathogenesis of the disease and facilitate further characterization of the cascade of molecular events elicited during infection.


Subject(s)
Biomarkers/metabolism , Endoplasmic Reticulum Stress , Leprosy, Lepromatous/diagnosis , Leprosy, Tuberculoid/diagnosis , Activating Transcription Factor 6/metabolism , Diagnosis, Differential , Endoplasmic Reticulum Chaperone BiP , Endoribonucleases/metabolism , Heat-Shock Proteins/metabolism , Humans , Leprosy/classification , Leprosy/metabolism , Leprosy, Lepromatous/metabolism , Leprosy, Tuberculoid/metabolism , Protein Serine-Threonine Kinases/metabolism , Signal Transduction , Up-Regulation , eIF-2 Kinase/metabolism
5.
Microbes Infect ; 19(11): 505-514, 2017 11.
Article in English | MEDLINE | ID: mdl-28684130

ABSTRACT

Our previous study has demonstrated that IL-10 may modulate both indoleamine 2,3-dioxygenase (IDO) and CD163 expression in lepromatous leprosy (LL) cells, favoring Mycobacterium leprae persistence through induction of regulatory pathways and iron storage. Here, we observed that in LL lesion cells there is an increase in the expression of proteins involved in iron metabolism such as hemoglobin (Hb), haptoglobin, heme oxygenase 1 and transferrin receptor 1 (TfR1) when compared to tuberculoid leprosy (BT) cells. We also found increased iron deposits and diminished expression of the iron exporter ferroportin 1 in LL lesion cells. Hemin, but not FeSO4 stimulation, was able to enhance M. leprae viability by a mechanism that involves IDO. Analysis of cell phenotype in lesions demonstrated a predominance of M2 markers in LL when compared with BT lesion cells. A positive correlation between CD163 and PPARG with the bacillary index (BI) was observed. In contrast, TNF, STAT1 and CSF2 presented a negative correlation with the BI. In summary, this study demonstrates that iron may regulate IDO expression by a mechanism that involves IL-10, which may contribute for the predominance of M2-like phenotype in LL lesions that favors the phagocytosis and maintenance of M. leprae in host cells.


Subject(s)
Indoleamine-Pyrrole 2,3,-Dioxygenase/physiology , Iron/physiology , Mycobacterium leprae/physiology , Adult , Female , Humans , Immunoblotting , Immunoenzyme Techniques , Indoleamine-Pyrrole 2,3,-Dioxygenase/metabolism , Iron/metabolism , Leprosy, Lepromatous/metabolism , Leprosy, Lepromatous/microbiology , Male , Middle Aged , Mycobacterium leprae/metabolism , Reverse Transcriptase Polymerase Chain Reaction
6.
s.l; Elsevier; 2017. 10 p. tab, graf.
Non-conventional in English | HANSEN, Sec. Est. Saúde SP, Hanseníase Leprosy, SESSP-ILSLPROD, Sec. Est. Saúde SP, SESSP-ILSLACERVO, Sec. Est. Saúde SP | ID: biblio-1052567

ABSTRACT

Our previous study has demonstrated that IL-10 may modulate both indoleamine 2,3-dioxygenase (IDO) and CD163 expression in lepromatous leprosy (LL) cells, favoring Mycobacterium leprae persistence through induction of regulatory pathways and iron storage. Here, we observed that in LL lesion cells there is an increase in the expression of proteins involved in iron metabolism such as hemoglobin (Hb), haptoglobin, heme oxygenase 1 and transferrin receptor 1 (TfR1) when compared to tuberculoid leprosy (BT) cells. We also found increased iron deposits and diminished expression of the iron exporter ferroportin 1 in LL lesion cells. Hemin, but not FeSO stimulation, was able to enhance M. leprae viability by a mechanism that involves IDO. Analysis of cell phenotype in lesions demonstrated a predominance of M2 markers in LL when compared with BT lesion cells. A positive correlation between CD163 and PPARG with the bacillary index (BI) was observed. In contrast, TNF, STAT1 and CSF2 presented a negative correlation with the BI. In summary, this study demonstrates that iron may regulate IDO expression by a mechanism that involves IL-10, which may contribute for the predominance of M2-like phenotype in LL lesions that favors the phagocytosis and maintenance of M. leprae in host cells.


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Immunoblotting , Leprosy, Lepromatous/metabolism , Leprosy, Lepromatous/microbiology , Immunoenzyme Techniques , Reverse Transcriptase Polymerase Chain Reaction , Indoleamine-Pyrrole 2,3,-Dioxygenase/physiology , Indoleamine-Pyrrole 2,3,-Dioxygenase/metabolism , Iron/physiology , Iron/metabolism , Mycobacterium leprae/physiology , Mycobacterium leprae/metabolism
7.
Fontilles, Rev. leprol ; 30(6): 571-590, sept.-dic. 2016. tab
Article in Spanish | IBECS | ID: ibc-159088

ABSTRACT

Se realizó un estudio descriptivo, longitudinal y retrospectivo con el objetivo de caracterizar el comportamiento de los pacientes con diagnóstico tardío de lepra notificados durante el período comprendido del 1 de enero del 2009 al 30 de septiembre del 2014 residentes en la provincia Camagüey. El universo de estudio estuvo constituido por 26 pacientes con diagnóstico tardío de lepra. Se determinó que el grupo de edad más afectado fue el de 60 años y más, con predominio del sexo masculino, escolaridad primaria y per cápita familiar regular. El mayor tiempo transcurrido entre los primeros síntomas y el diagnóstico fue de 1 a 3 años y la mancha anestésica constituyó el signo más frecuente de inicio de la enfermedad. Aproximadamente la mitad de los pacientes estuvieron evaluados por especialistas de Medicina General Integral antes del diagnóstico. Predominó la lepra lepromatosa, la discapacidad grado I, de localización en los pies y de tipo anestesia. Alrededor de las tres cuartas partes de los pacientes fueron detectados de forma espontánea y casi la mitad de los mismos presentó un tiempo de permanencia en el área de salud de entre 1 y 2 años


A descriptive, longitudinal and retrospective study was made with the aim of characterizing the behavior of the patients with a diagnosis of late leprosy notified during the period of January 1st, 2009 up to September 30th, 2014 in the county of Camagüey. The study consisted of 26 patients with a late diagnosis of leprosy. It was determined that the most affected age group was that of 60 years and above, with prevalence of the men, primary education and middle family per capita. The longest delay between first symptoms and diagnosis went from 1 to 3 years and the anesthetic patch constituted the most frequent sign as initial start of the illness. Approximately half of the patients were evaluated by specialists of Integral General Medicine before the diagnosis. The most frequent type was lepromatous leprosy, disability grade I prevailed mainly on feet. Approximately three fourths of the patients were detected in a spontaneous way and almost half of them were present in the area between 1 and 2 years


Subject(s)
Humans , Male , Adult , Delayed Diagnosis/classification , Epidemiology, Descriptive , Leprosy, Lepromatous/metabolism , Leprosy, Lepromatous/pathology , Granulomatous Disease, Chronic/pathology , Peripheral Nerves/cytology , Respiratory Tract Diseases/pathology , Delayed Diagnosis/prevention & control , Cuba/ethnology , Longitudinal Studies , Retrospective Studies , Leprosy, Lepromatous/diagnosis , Leprosy , Granulomatous Disease, Chronic/metabolism , Peripheral Nerves/metabolism , Respiratory Tract Diseases/complications
8.
Fontilles, Rev. leprol ; 30(6): 591-596, sept.-dic. 2016. ilus
Article in Spanish | IBECS | ID: ibc-159089

ABSTRACT

La lepra puede presentar diversas y complejas manifestaciones clínicas. Las lesiones cutáneas más frecuentemente encontradas son: máculas, pápulas, placas, nódulos y tubérculos. El propósito de esta comunicación es resaltar una forma de presentación atópica de lepra lepromatosa, en un adulto joven de sexo masculino, cuya lesiones iniciales eran pápulas excoriadas en superficie simulando una urticaria papular/prurigo simple. En este caso en particular, la anatomía patológica fue determinante para el diagnóstico correcto. Hacemos hincapié en que la lepra lepromatosa es una «gran simuladora» y los clínicos deberían estar alertas ante estas formas de manifestación rara, que ocurren en ciertas regiones endémicas


Leprosy may have diverse and complex clinical manifestations. Skin lesions most commonly found are: macules, papules, plaques, nodules and tubers. The purpose of this communication is to highlight a form of atypical presentation of lepromatous leprosy, in a young adult male, whose initial lesions were excoriated papules on surface simulating a prurigo/papular urticaria. In this particular case, the pathology was decisive for correct diagnosis. We emphasize that lepromatous leprosy is a great imitator and clinicians should be aware of these rare forms of manifestation, occurring in certain endemic areas


Subject(s)
Humans , Male , Young Adult , Leprosy, Lepromatous/pathology , Leprosy, Lepromatous/transmission , Skin Abnormalities/pathology , Leprosy, Tuberculoid/pathology , Therapeutics/methods , Leprosy, Lepromatous/diagnosis , Leprosy, Lepromatous/metabolism , Skin Abnormalities/diagnosis , Leprosy, Tuberculoid/transmission , Athletes/classification , Soccer/classification , Paraguay/ethnology , Therapeutics
9.
Indian J Lepr ; 88(2): 129-131, 2016 04.
Article in English | MEDLINE | ID: mdl-29757546

ABSTRACT

Elastophagocytosis is the engulfment of the elastic fibres by the histiocytes, multinucleated giant cells, or both. The cutaneous lesions showing elastophagocytosis are annular elastolytic giant cell granuloma, actinic keratoses, persistent insect-bite reactions, elastosis perforans serpiginosa, foreign body granuloma. Occasionally, it may occur in infectious diseases like leprosy, granulomatous syphilis, North-American blastomycosis, bacterial folliculitis, and cutaneous leishmaniasis. We report a case of lepromatous leprosy with necrotic erythema nodosum leprosum with secondary anetoderma. Histopathology from the atrophic macule of anetoderma revealed periappendageal, perineural infiltration, elastophagocytosis and reduction in elastic fibres.


Subject(s)
Elastic Tissue/metabolism , Leprosy, Lepromatous/diagnosis , Phagocytosis , Anetoderma/diagnosis , Anetoderma/etiology , Anetoderma/metabolism , Anetoderma/pathology , Elastic Tissue/pathology , Erythema Nodosum/diagnosis , Erythema Nodosum/etiology , Erythema Nodosum/metabolism , Erythema Nodosum/pathology , Histiocytes/physiology , Humans , Leprosy, Lepromatous/complications , Leprosy, Lepromatous/metabolism , Leprosy, Lepromatous/pathology , Male , Middle Aged
10.
Article in English | MEDLINE | ID: mdl-26515838

ABSTRACT

BACKGROUND: Leprosy is a chronic granulomatous infection caused by Mycobacterium leprae, an intracellular parasite that resides within macrophages and cannot be eliminated effectively. Solute carrier family 11a member 1 (Slc11a1) and inducible nitric oxide synthase (iNOS), both expressed in macrophages, play major roles in host defense against several intracellular pathogens. However, the roles of these molecules in natural infection with M. leprae remain unknown. OBJECTIVE: We aimed to investigate the expression of Slc11a1 and iNOS in macrophages (CD68+ cells) infiltrating skin lesions in leprosy. METHODS: Skin biopsies from 48 Mexican patients of leprosy [(33 lepromatous (LL), 15 tuberculoid (TT)] and from 10 healthy controls, were subjected to immunohistochemistry to determine expression of CD68, Slc11a1 and iNOS. RESULTS: We found a high expression of Slc11a1 and iNOS in most lepromatous leprosy samples. In tuberculoid leprosy samples, Slc11a1 expression was moderate or low, and that of iNOS was almost always low. In addition, Slc11a1 and iNOS expression levels were positively associated with bacillary loads in lepromatous leprosy lesions (P=0.05). CONCLUSIONS: These observations suggest that M. leprae infection promotes the expression of Slc11a1 and iNOS in macrophages and that lepromatous leprosy can occur despite this response.


Subject(s)
Cation Transport Proteins/analysis , Leprosy, Lepromatous/metabolism , Leprosy, Tuberculoid/metabolism , Macrophages/chemistry , Nitric Oxide Synthase Type II/analysis , Adult , Aged , Antigens, CD/analysis , Antigens, Differentiation, Myelomonocytic/analysis , Case-Control Studies , Female , Humans , Leprosy, Lepromatous/pathology , Leprosy, Tuberculoid/pathology , Male , Middle Aged
11.
J Invest Dermatol ; 135(10): 2410-2417, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26030183

ABSTRACT

The mechanisms by which intracellular pathogens trigger immunosuppressive pathways are critical for understanding the pathogenesis of microbial infection. One pathway that inhibits host defense responses involves the induction of type I interferons and subsequently IL-10, yet the mechanism by which type I IFN induces IL-10 remains unclear. Our studies of gene expression profiles derived from leprosy skin lesions suggested a link between IL-27 and the IFN-ß induced IL-10 pathway. Here, we demonstrate that the IL-27p28 subunit is upregulated following treatment of monocytes with IFN-ß and Mycobacterium leprae, the intracellular bacterium that causes leprosy. The ability of IFN-ß and M. leprae to induce IL-10 was diminished by IL-27 knockdown. Additionally, treatment of monocytes with recombinant IL-27 was sufficient to induce the production of IL-10. Functionally, IL-27 inhibited the ability of IFN-γ to trigger antimicrobial activity against M. leprae in infected monocytes. At the site of disease, IL-27 was more strongly expressed in skin lesions of patients with progressive lepromatous leprosy, correlating and colocalizing with IFN-ß and IL-10 in macrophages. Together, these data provide evidence that in the human cutaneous immune responses to microbial infection, IL-27 contributes to the suppression of host antimicrobial responses.


Subject(s)
Interferon-beta/pharmacology , Interleukin-10/metabolism , Interleukin-27/metabolism , Leprosy, Lepromatous/drug therapy , Leprosy, Lepromatous/metabolism , Mycobacterium leprae/metabolism , Animals , Biomarkers/metabolism , Cells, Cultured , Cytokines/metabolism , Enzyme-Linked Immunosorbent Assay , Humans , Immunosuppressive Agents/pharmacology , Interleukin-27/pharmacology , Leprosy, Lepromatous/pathology , Mice , Microscopy, Confocal , Models, Animal , Monocytes/cytology , Monocytes/drug effects , Mycobacterium leprae/pathogenicity , Prognosis , RNA, Small Interfering/metabolism , Real-Time Polymerase Chain Reaction/methods , Sampling Studies , Sensitivity and Specificity , Transfection
12.
Acta Trop ; 149: 227-31, 2015 Sep.
Article in English | MEDLINE | ID: mdl-26051909

ABSTRACT

Leprosy is an infectious-contagious disease whose clinical evolution depends on the immune response pattern of the host. Adhesion molecules and leukocyte migration from blood to tissue are of the utmost importance for the recognition and elimination of infectious pathogens. Selectins are transmembrane glycoproteins that share a similar structural organization and can be divided into three types according to their site of expression. The biopsies were cut into 5µm thick sections and submitted to immunohistochemistry using antibodies against E-selectin and P-selectin. The number of E-selectin-positive cells was significantly higher in the tuberculoid form than in the lepromatous form. The immunostaining pattern of P-selectin differed from that of E-selectin. Analysis showed a larger number of endothelial cells expressing CD62P in the lepromatous form compared to the tuberculoid form. The presence of these adhesins in the endothelium contributing to or impairing the recruitment of immune cells to inflamed tissue and consequently influences the pattern of immune response and the clinical presentation of the disease.


Subject(s)
E-Selectin/metabolism , Endothelial Cells/metabolism , Endothelium, Vascular/metabolism , Leprosy, Lepromatous/metabolism , Leprosy, Tuberculoid/metabolism , P-Selectin/metabolism , Skin/metabolism , Cell Adhesion Molecules , Endothelium, Vascular/cytology , Humans , Immunohistochemistry
15.
Fontilles, Rev. leprol ; 30(1): 31-43, ene.-abr. 2015.
Article in Spanish | IBECS | ID: ibc-139973

ABSTRACT

La lepra, aunque actualmente está desapareciendo, no ha sido derrotada todavía en Surinam. En la época colonial fue un gran problema para el gobierno colonial y la población, siendo la mayoría de pacientes (en la época pre-abolicionista) esclavos. En el siglo XVIII se estableció un sistema de control que ya incluía la en la legislación la detección y el confinamiento como métodos importantes. Los médicos holandeses que ejercían en Surinam durante el siglo XVIII y primera mitad del siglo XIX propusieron modelos contagionistas de contención que sugieren que la lepra era causada por una mezcla de factores, siendo la infección uno de ellos. Pero durante la primera mitad del siglo XIX, los investigadores europeos rechazaron mayoritariamente la infección y prevaleció el anti-contagionismo, considerando la herencia y los factores medioambientales como su causa. Al mismo tiempo, en Surinam - puesto que la lepra estaba incontrolada - la lucha contra la lepra se reforzó promulgando leyes implacables para perseguir e identificar a los leprosos. A su vez, Charles Louis Drognat-Landré defendió el punto de vista (tesis Utrecht) de que solamente la infección es la causa de la lepra. Su argumento sobre el contagionismo fue rechazado en Holanda, pero posteriormente publicó sus ideas en francés y así llegaron a ser más conocidas internacionalmente e influyeron en el noruego Hansen. Este descubrió algunos años después el microorganismo causal. Se afirma que hay una relación entre el desarrollo de una forma de contagionismo típico surimanés, un sistema de control de la lepra brutal y la estructura política autocrática, no liberal (hacia los esclavos) de la colonia holandesa de Surinam


Leprosy is nowadays a disappearing but not yet defeated disease in Suriname. In colonial times it was a burden for colonial government and people, the majority of patients (in preabolition times) being slaves. In the 18th century a control system was established, with detection and isolation, anchored in legislation, as major methods. Dutch physicians working in Suriname in the 18th and first half of the 19th century proposed contingent contagionistic models, according to which leprosy was caused by a mixture of factors, infection being one of them. But in the first half of the 19th century European researchers generally denied infection as the cause of leprosy and the paradigm of anti-contagionism prevailed, considering heredity and environmental factors as its cause. At the same time in Suriname - because leprosy appeared uncontrollable - the fight against the disease was reinforced by promulgating more relentless laws to hunt and identify lepers. In line with this, the Suriname born Charles Louis Drognat-Landré defended the view (thesis Utrecht) that infection is the one and only cause of leprosy. His extreme contagionism was sharply rejected in The Netherlands, but then he published his ideas in French and so could reach the international scene and influence the Norwegian Hansen. The latter discovered the culpable micro-organism a few years later. We claim a correlation between the development of a typical Surinamese form of contagionism, the brutal leprosy control system and the autocratic, non-liberal (towards the slaves) political structure of the Dutch colony Suriname


Subject(s)
Female , Humans , Male , Leprosy, Lepromatous/metabolism , Leprosy, Lepromatous/transmission , Suriname/ethnology , Enslavement/ethnology , Enslavement/history , History, 19th Century , Public Health/economics , Public Health , Focus Groups/methods , Leprosy, Lepromatous/complications , Leprosy, Lepromatous/diagnosis , Suriname/epidemiology , Enslavement/economics , Enslavement/psychology , Public Health/legislation & jurisprudence , Public Health/statistics & numerical data , Focus Groups
16.
Fontilles, Rev. leprol ; 30(1): 45-61, ene.-abr. 2015. tab, graf, ilus
Article in Spanish | IBECS | ID: ibc-139974

ABSTRACT

Antecedentes: Los niños son el grupo más vulnerable a la lepra y la lepra infantil refleja la transmisión de la enfermedad en la comunidad, así como la eficacia de sus programas de control. Objetivos: Estudiar las tendencias epidemiológicas y clínicas de los casos de lepra infantil en un hospital del norte de la India durante 2001-2011. Métodos: Se llevó a cabo un estudio retrospectivo analizando las historias clínicas de niños con lepra de 18 años o menores, registrados en los archivos de esta institución durante un período de 11 años. Las características demográficas y de la enfermedad, incluyendo edad, sexo, historia de contacto, duración de la enfermedad, patrón clínico, parámetros bacteriológicos e histopatológicos, reacciones y discapacidades fueron registradas mediante un formato prediseñado. Resultados: Durante este período se registraron 1225 casos de lepra, de los cuales 59 (4·81%) eran niños. La edad media de los pacientes fue de 10·06 ± 3·35 años con mayor cantidad de hombres (3·9:1). La historia de contactos con un caso de lepra estaba presente en 15 (25·4%) pacientes. La duración media de la enfermedad antes del diagnóstico fue de 18·5 meses (rango: 1 - 70 meses). La forma más típica fue la borderline tuberculoide (BT) en 40 niños (67·8%), seguida por la lepromatosa (LL) en 7 (11·9%), la borderline lepromatosa (BL) en 6 (10·1%), neurítica pura (PNL) en 2 (3·4%), tuberculoide (TT), borderline-borderline (BB), histioide y lepra indeterminada con 1 paciente cada una (1·7%). Las lesiones se localizaron en las extremidades superiores en 32 (54·2%), en extremidades inferiores en 29 (49·2%), en la cara en 27 (45·8%) y en el tronco en 26 (44·1%) pacientes. Se detectó una lesión única en 23 (39%), 2 - 5 lesiones en 12 (20·3%) y más de cinco lesiones en 22 (37·3%) niños. La baciloscopia fue positiva en 17 (28·8%) pacientes. Las leprorreacciones se detectaron en 20 pacientes (33·9%), de los cuales 14 (70%) presentaron tipo 1, y seis (30%) tipo 2. Se detectó engrosamiento del tronco nervioso periférico en 48 (81·4%) niños, de los cuáles 27 (56·3%) presentaron más de un nervio engrosado y 21 (43·7%) solamente un nervio. Hubo neuritis en 9 (15·3%) y discapacidad (tanto grado 1 como 2) al confirmar el diagnóstico en 24 (40·7%) pacientes. Seis (10·2%) niños no completaron el tratamiento. Se observaron tres casos (5·1%) de recidivas. Conclusiones: Los casos de lepra infantil y sus complicaciones siguen estando presentes en cantidades preocupantes en la India y esto sugiere la existencia de posibles deficiencias en los programas nacionales con el objetivo de la eliminación. Enfatizamos la importancia de los esfuerzos continuados y sostenidos para la detección precoz en la comunidad en general y seguimiento de los niños susceptibles entre los convivientes de casos de lepra en la era post-eliminación


Background: Children are believed to be the most vulnerable group for leprosy and childhood leprosy reflects disease transmission in the community as well as the efficiency of ongoing disease control programmes. Objectives: To study the epidemiological and clinical trends of childhood cases of leprosy at a tertiary care hospital in North India during 2001 - 2011. Methods: A retrospective study was undertaken analysing the clinic records of children with leprosy less than or equal to 18 years registered at the leprosy clinic of this institute over an 11- year period. Demographic and disease characteristics including age, sex, history of contact, duration of disease, clinical pattern, bacteriological and histopathological parameters, reactions and disabilities were noted from a predesigned format. Results: A total of 1225 cases of leprosy were registered during this period, of whom 59 (4·81%) were children. The mean age of the patients was 10·06 ± 3·35 years with a male preponderance (3·9:1). History of close contact with a leprosy case was present in 15 (25·4%) patients. Mean duration of illness before diagnosis was 18·5 months (range: 1 - 70 months). Borderline tuberculoid (BT) was the commonest clinical type in 40 children (67·8%), followed by lepromatous (LL) in 7 (11·9%), borderline lepromatous (BL) in 6 (10·1%), pure neuritic (PNL) in 2 (3·4%), tuberculoid (TT), mid-borderline (BB), histoid and indeterminate leprosy in 1 patient (1·7%) each. Lesions were located over upper extremity in 32 (54·2%), lower extremity in 29 (49·2%), face in 27 (45·8%) and trunk in 26 (44·1%) patients. A single lesion was observed in 23 (39%), 2 - 5 lesions in 12 (20·3%) and more than five lesions in 22 (37·3%) children. The slit skin smear was positive in 17 (28·8%) patients. Lepra reactions were observed in 20 patients (33·9%), of whom 14 (70%) had Type 1, and six (30%) had Type 2 lepra reaction. Thickened peripheral nerve trunks were present in 48 (81·4%) children, of which, 27 (56·3%) had more than one thickened nerve and 21 (43·7%) had only a single nerve involved. Neuritis occurred in 9 (15·3%) and disability (both grade 1 and 2) at the time of diagnosis was noted in 24 (40·7%) patients. Six (10·2%) children defaulted from treatment. Three cases (5·1%) of relapse were observed


Subject(s)
Child , Humans , Leprosy, Lepromatous/congenital , Leprosy, Lepromatous/transmission , Child Health/legislation & jurisprudence , India/ethnology , Pharmaceutical Preparations/administration & dosage , Neuritis/pathology , Leprosy, Lepromatous/complications , Leprosy, Lepromatous/metabolism , Child Health/statistics & numerical data , India/epidemiology , Pharmaceutical Preparations/economics , Neuritis/metabolism , Retrospective Studies
18.
Science ; 339(6126): 1448-53, 2013 Mar 22.
Article in English | MEDLINE | ID: mdl-23449998

ABSTRACT

Type I interferons (IFN-α and IFN-ß) are important for protection against many viral infections, whereas type II interferon (IFN-γ) is essential for host defense against some bacterial and parasitic pathogens. Study of IFN responses in human leprosy revealed an inverse correlation between IFN-ß and IFN-γ gene expression programs. IFN-γ and its downstream vitamin D-dependent antimicrobial genes were preferentially expressed in self-healing tuberculoid lesions and mediated antimicrobial activity against the pathogen Mycobacterium leprae in vitro. In contrast, IFN-ß and its downstream genes, including interleukin-10 (IL-10), were induced in monocytes by M. leprae in vitro and preferentially expressed in disseminated and progressive lepromatous lesions. The IFN-γ-induced macrophage vitamin D-dependent antimicrobial peptide response was inhibited by IFN-ß and by IL-10, suggesting that the differential production of IFNs contributes to protection versus pathogenesis in some human bacterial infections.


Subject(s)
Interferon-beta/immunology , Interferon-gamma/immunology , Leprosy, Lepromatous/immunology , Leprosy, Tuberculoid/immunology , Mycobacterium leprae/immunology , 25-Hydroxyvitamin D3 1-alpha-Hydroxylase/genetics , 25-Hydroxyvitamin D3 1-alpha-Hydroxylase/metabolism , Antimicrobial Cationic Peptides/genetics , Antimicrobial Cationic Peptides/metabolism , Humans , Interferon-beta/genetics , Interferon-beta/metabolism , Interferon-gamma/genetics , Interferon-gamma/metabolism , Interleukin-10/genetics , Interleukin-10/metabolism , Leprosy, Lepromatous/genetics , Leprosy, Lepromatous/metabolism , Leprosy, Tuberculoid/genetics , Leprosy, Tuberculoid/metabolism , Microbial Viability , Monocytes/immunology , Monocytes/metabolism , Mycobacterium leprae/physiology , RNA, Messenger/genetics , RNA, Messenger/metabolism , Receptors, Calcitriol/genetics , Receptors, Calcitriol/metabolism , Transcriptome , Tuberculosis/genetics , Tuberculosis/immunology , Up-Regulation , beta-Defensins/genetics , beta-Defensins/metabolism , Cathelicidins
19.
Lepr Rev ; 84(3): 176-85, 2013 Sep.
Article in English | MEDLINE | ID: mdl-24428111

ABSTRACT

Histoid leprosy is a rare multibacillary form that presents with disseminated papule-nodular cutaneous lesions. To study the inflammatory infiltrate of the histoid form and to compare it with other lepromatous forms, we performed histological and immunohistochemical analysis on skin biopsies. Fifteen patients were included for histopathological analysis (10 histoid and five lepromatous) via the haematoxylin-eosin and Ziehl-Neelsen-Faraco stains. Thus, immunohistochemical techniques using immunoperoxidase assay were performed for: anti-BCG, anti-M. leprae, anti-CD8, anti-CD3, anti-CD20, anti-S100, anti-CD1a, anti-CD68 and antivimentin. Spindle cells were present in all histoid patients. A pseudocapsule was observed in half of both studied forms. A comparison using the Ziehl-Neelsen-Faraco stain to evaluate anti-BCG and anti-M.leprae showed no major differences. The CD3+ cells were more pronounced in the histoid form than the lepromatous form. There was greater immunoreactivity toward CD8+ cells in the histoid form, as well as the CD20+ cell count. A similar count of S100+ cells in the epidermis of both leprosy forms was observed. There was a slight increase of dendritic cells in the histoid patients in the superficial and deep dermis. For CD1a marker, we observed expression in the epidermis and superficial dermis in both forms. A diffuse and intense infiltrate of CD68+ cells was also observed in the histoid and lepromatous forms. The high positivity for vimentin did not allow for a positive cell count. We concluded that the activation of both the cellular and humoral response is more pronounced in the histoid form because the T and B cells showed greater infiltration than those in the lepromatous form. The activation of dendritic and Langerhans cells is similar in both forms. The spindle cells likely belong to the macrophage population, thus maintaining phagocytic ability. The quantities of pseudocapsules and bacilli are similar and cannot serve as criteria for diagnosis.


Subject(s)
Leprosy, Lepromatous/metabolism , Leprosy, Lepromatous/pathology , Leprosy, Multibacillary/metabolism , Leprosy, Multibacillary/pathology , Adult , Female , Humans , Immunohistochemistry , Male , Middle Aged , Retrospective Studies , Skin/chemistry , Skin/metabolism , Skin/pathology
20.
Diagn Cytopathol ; 41(4): 366-8, 2013 Apr.
Article in English | MEDLINE | ID: mdl-21932352

ABSTRACT

Erythema nodosum leprosum (ENL) or type 2 lepra reaction is an inflammatory reaction, which may occur in the course of hanseniasis, may compel the patient to seek medical attention and may result in nerve function impairment and subsequent disability. Thus, recognition and timely management of these patients is critical in order to avoid permanent disability. Fine-needle aspiration cytology is simple and effective tool that aids in the correct diagnosis and management of ENL. Herein, we present two cases of ENL, one with typical and another with atypical presentation.


Subject(s)
Erythema Nodosum/diagnosis , Leprosy, Lepromatous/diagnosis , Mycobacterium leprae/isolation & purification , Skin/microbiology , Biopsy, Fine-Needle , Child , Erythema Nodosum/metabolism , Female , Humans , Leprosy, Lepromatous/metabolism , Macrophages/pathology , Male , Mycobacterium leprae/pathogenicity , Neutrophils/metabolism , Skin/metabolism , Skin Diseases, Bacterial/diagnosis , Staining and Labeling
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