RESUMO
Leprosy is the most common treatable peripheral nerve disorder worldwide, with periods of acute neuritis leading to functional impairment of limbs and stigmatizing deformities. The nerve involvement in leprosy reactions, if recognized early and promptly treated with steroids and nerve release surgery, can be reversible. Currently, the nerve assessment in leprosy relies mainly on clinical assessment and nerve conduction studies. High-resolution ultrasonography (HRUS) of peripheral nerves is finding wider application in the differential diagnosis of peripheral neuropathy. HRUS provides a noninvasive tool that gives information on location and degree of nerve enlargement, nerve morphologic alterations, echo texture, fascicular pattern, and vascularity of the nerve, which mirrors the histologic changes. HRUS is amenable to studying structural changes in nerve sites that cannot be biopsied for histopathologic examination and is more cost effective than magnetic resonance imaging. So far other there are only five studies available on the sonographic findings in leprosy. These findings are reviewed and the technique of HRUS is described in this paper, with a recommendation of a standard protocol and proforma.
Assuntos
Humanos , Hanseníase/diagnóstico por imagem , UltrassonografiaRESUMO
Can leprosy be eliminated? This paper considers the question against the background of the WHO programme to eliminate leprosy. In 1991 the World Health Assembly set a target of eliminating leprosy as a public health problem by 2000. Elimination was defined as reaching a prevalence of < 1 case per 10 000 people. The elimination programme has been successful in delivering highly effective antibiotic therapy worldwide. However, despite this advance, new-case detection rates remain stable in countries with the highest rates of endemic leprosy, such as Brazil and India. This suggests that infection has not been adequately controlled by antibiotics alone. Leprosy is perhaps more appropriately classed as a chronic stable disease than as an acute infectious disease responsive to elimination strategies. In many countries activities to control and treat leprosy are being integrated into the general health-care system. This reduces the stigma associated with leprosy. However, leprosy causes long-term immunological complications, disability and deformity. The health-care activities of treating and preventing disabilities need to be provided in an integrated setting. Detecting new cases and monitoring disability caused by leprosy will be a challenge. One solution is to implement long-term surveillance in selected countries with the highest rates of endemic disease so that an accurate estimate of the burden of leprosy can be determined. It is also critical that broad-based research into this challenging disease continues until the problems are truly solved.
Assuntos
Humanos , Controle de Doenças Transmissíveis , Desenvolvimento de Programas , Hansenostáticos , Hanseníase , Mycobacterium leprae , Organização Mundial da Saúde , Prestação Integrada de Cuidados de Saúde , Prevalência , Saúde Global , Vigilância da PopulaçãoRESUMO
To investigate genetic diversity in a bacterial population, we measured the copy numbers of simple sequence repeats, or microsatellites, in Mycobacterium leprae from patients living in and around Hyderabad, India. Three microsatellite loci containing trinucleotide or dinucleotide repeats were amplified from infected tissues, and the copy numbers were established by sequence analysis. Extensive diversity was observed in a cross-sectional survey of 33 patients, but closely related profiles were found for members of a multicase family likely to share a common transmission source. Sampling of multiple tissues from single individuals demonstrated identical microsatellite profiles in the skin, nasal cavity, and bloodstream but revealed differences at one or more loci for M. leprae present in nerves. Microsatellite mapping of M. leprae represents a useful tool for tracking short transmission chains. Comparison of skin and nerve lesions suggests that the evolution of disease within an individual involves the expansion of multiple distinct subpopulations of M. leprae.
Assuntos
Masculino , Feminino , Humanos , Dosagem de Genes , Especificidade da Espécie , Estudos Transversais , Família , Hanseníase , Mycobacterium leprae , Reação em Cadeia da Polimerase , Repetições de Microssatélites , Técnicas de Tipagem Bacteriana , Variação GenéticaRESUMO
Mycobacterium leprae, the causative agent of leprosy invades Schwann cells of the peripheral nerves leading to nerve damage and disfigurement, which is the hallmark of the disease. Wet experiments have shown that M. leprae binds to a major peripheral nerve protein, the myelin P zero (P0). This protein is specific to peripheral nerve and may be important in the initial step of M. leprae binding and invasion of Schwann cells which is the feature of leprosy. Though the receptors on Schawann cells, cytokines, chemokines and antibodies to M. leprae have been identified the molecular mechanism of nerve damage and neurodegeneration is not clearly defined. Recently pathogen and host protein/nucleotide sequence similarities (molecular mimicry) have been implicated in neurodegenerative diseases. The approach of the present study is to utilise bioinformatic tools to understand leprosy nerve damage by carrying out sequence and structural similarity searches of myelin P0 with leproma and other genomic database. Since myelin P0 is unique to peripheral nerve, its sequence and structural similarities in other neuropathogens have also been noted. Comparison of myelin P0 with the M. leprae proteins revealed two characterised proteins, Ferrodoxin NADP reductase and a conserved membrane protein, which showed similarity to the query sequence. Comparison with the entire genomic database (www.ncbi.nlm.nih.gov) by basic local alignment search tool for proteins (BLASTP) and fold classification of structure-structure alignment of proteins (FSSP) searches revealed that myelin P0 had sequence/structural similarities to the poliovirus receptor, coxsackie-adenovirus receptor, anthrax protective antigen, diphtheria toxin, herpes simplex virus, HIV gag-1 peptide, and gp120 among others. These proteins are known to be associated directly or indirectly with neruodegeneration. Sequence and structural similarities to the immunoglobin regions of myelin P0 could have implications in host-pathogen interactions, as it has homophilic adhesive properties. Although these observed similarities are not highly significant in their percentage identity, they could be functionally important in molecular mimicry, receptor binding and cell signaling events involved in neurodegeneration.
Assuntos
Humanos , Biologia Computacional , Conformação Proteica , Dados de Sequência Molecular , Doenças Neurodegenerativas , Hanseníase , Ligação Proteica , Mimetismo Molecular , Modelos Moleculares , Mycobacterium leprae , Proteína P0 da Mielina , Proteínas de Bactérias , Proteínas de Membrana , Proteômica , Receptores Virais , Sequência de AminoácidosRESUMO
The trigeminal and great auricular nerves which supply sensation to the face are affected in leprosy. No objective sensory testing methods have been devised for testing sensation in the face. Testing for corneal sensation to ascertain trigeminal nerve or visualization and palpation of the great auricular nerve alone may not be enough to establish the involvement of these nerves. In a sample of leprosy patients, face sensation threshold measurements were done using a set of three Semmes-Weinstein (SW) monofilaments that gave a force of 0.05-0.07, 0.2 and 2 g. Sensation was tested by three examiners and intra- and inter-observer testing was used as a means to validate the findings. Within the limitations of this study, the results indicate that use of SW monofilaments is a fairly reliable and repeatable method for sensory testing in the face. During follow up, a single filament with a force of 0.5-0.7 g (2.83 marking number in SW filament or any other filament with a corresponding gram force) could be used to assess sensation. A simple procedure of quantifying sensation in these nerves is suggested. A method to incorporate trigeminal or great auricular nerve sensory testing into the existing sensory assessment charts is also discussed.
Assuntos
Hanseníase/complicações , Hanseníase/fisiopatologia , Nervo Trigêmeo/fisiopatologiaRESUMO
To understand Mycobacterium leprae-peripheral nerve interaction, we have investigated the binding of M. leprae to rat peripheral nerve proteins in an in vitro model using 32P-phosphorylated proteins of the peripheral nerve. Intact M. leprae binds to a major phosphorylated protein of 28-30 kDa and, to a minor extent, to a few proteins of molecular weight 45-55 kDa. This binding was more specific for M. leprae since only insignificant binding was observed with other bacteria, such as M. bovis or Escherichia coli. M. leprae did not show binding to several phosphorylated proteins of the rat brain. The 28-30-kDa binding protein of the rat peripheral nerve was found to be a glycoprotein by concanavalin A-Sepharose column chromatography.
Assuntos
Fosfoproteínas/metabolismo , Fosfoproteínas/química , Mycobacterium leprae/metabolismoRESUMO
The classification of leprosy into multibacillary (MB) and paucibacillary (PB) patients in almost all clinics is entirely dependent on clinical examination. In a study of 21 patients clinically classified as borderline tuberculoid (BT) and, therefore, belonging to the PB group, skin smears and skin and nerve biopsies were examined. Four patients did not have any histopathological evidence of leprosy. Skin smears showed that 1 patient was positive for acid-fast bacilli (AFB), 2 skin biopsies belonged to the borderline lepromatous (BL) category and showed AFB in their lesions, and AFB were present in 10 nerve biopsies classified as BL. It is possible that reported relapses among PB patients may be in those patients with demonstrable AFB in the lesions, including nerves. A careful follow-up study of this particular group of patients after PB multidrug therapy is suggested to resolve this question.