La Lepra, 2.000 años despues. !
The Leprosy, 2.000 years later. !
LEPRA EN DEDO PULGAR DE MANO DERECHA CON INCAPACIDAD FUNCIONAL
=================
Hola amigos de la red, DERMAGIC hoy con el tema de la ENFERMEDAD DE HANSEN (LEPRA)2.000 AÑOS DESPUÉS. Realmente esta enfermedad tiene mas de 2.000 años de evolución en nuestro planeta pues las primeras descripciones de la enfermedad datan del siglo XVI antes de Cristo, encontrándose las primeras referencias en el libro sagrado de la antigua India. En la Biblia aparece reseñada en el LEVÍTICO.
Muchos años han pasado y muchas investigaciones se han hecho, enfermedad de difícil tratamiento, ancestral y de distribución mundial que figura en la Biblia lo cual le da ese toque apocalíptico a esta temida enfermedad, causa de discriminación social aun en nuestros días.
Fue ARMAUER HANSEN quien descubrió el bacilo que lleva su nombre en el año de 1.873, Bacilo de HANSEN, el cual es una Micobacteria, a la que se denomino MYCOBACTERIUM LEPRAE. Desde ese momento no han parado las investigaciones sobre esta enfermedad.
Desde el aceite de Chalmoogra introducido por el egipcio Tortoulis Bey en 1.894 para tratar la enfermedad hasta la fabricación de diferentes vacunas (inmunoterapia) que están siendo utilizadas hoy día, pasaron muchos años.
En estas 108 referencias bibliográficas se resumen muchos de los nuevos avances en el campo de la enfermedad, nuevas terapias, nuevos hallazgos pero la enfermedad sigue "viva", no ha sido erradicada de la faz de la tierra.
Eso es lo primero que debo reseñar, si bien es cierto los casos han disminuido por la efectiva labor de la Organización Mundial de la Salud (OMS) a nivel mundial, y los avances científicos la enfermedad de HANSEN todavía prevalece en el mundo, en unas regiones mas que otras.
Para el 2.015 se reportaron 215.000 mil casos nuevos de lepra en el mundo, correspondiéndole el pais INDIA el mayor numero de casos con un 60%, otros paises bastante afectados son BRASIL e INDONESIA.
El “Día Mundial de la Lucha contra la Lepra” se celebra el último Domingo de Enero de cada año. Es una fecha para informar y concientizar a la población respecto a esta enfermedad.
Fue promovido por el periodista Francés Raoul Follereau en favor de los enfermos de lepra y se declaro el 31 de enero 1.954 oficialmente el primer “Día Mundial de la lucha contra la Lepra”. Su objetivo era sensibilizar sobre la existencia de esta enfermedad y alejar la imagen negativa que se tenía de los afectados.
Los aspectos a resaltar son:
1.) En el año 2.008 fue descubierto otro MYCOBACTERIUM diferente genéticamente al LEPRAE, como agente causal de la lepra, por el Departamento de Medicina de Laboratorio de la Universidad de Texas, por Han y Colaboradores se le denominó MYCOBACTERIUM LEPROMATOSIS, hallazgo hecho en MÉXICO, ESTADOS UNIDOS y posteriormente SINGAPUR, INDIA y encontrado también en las ardillas rojas de las ISLAS BRITÁNICAS, las cuales hoy día son un reservorio para la lepra en estas islas.
2.) La aparición de resistencia a la MTD (Multi Drug Therapy) tratamiento CLÁSICO con Diaminodifenilsulfona (DDS), Clofazimina y rifampicina, también resistencia a tratamiento con MINOCICLINA Y OFLOXACINA.) con los nuevos ESQUEMAS ordenados por la organización mundial de la salud (OMS).
3.) La comprobación de que antibióticos como la OFLOXACINA, MINOCICLINA, ÁCIDO CLAVULANICO mas AMOXACILINA Y CLARITROMICINA son altamente bactericidas contra el Mycobacterium leprae, de hecho la MINOCICLINA Y OFLOXACINA. Hoy día son utilizadas en el tratamiento. también La aparición de nuevas drogas con actividad antimicrobacteriana como las RIMINOFENAZINAS.
4.) El éxito de la Talidomida para tratar el ERITEMA NODOSO LEPROSO, que motivo su comercialización (otra vez) EN LOS ESTADOS UNIDOS DE NORTEAMÉRICA desde 1.998. También La utilización de Antileucotrienos como el ZAFIRLUKAST para tratar la Reacción leprosa, y otras nuevas como el ETARNECEPT (Inhibidor del factor de necrosis tumoral).
5.) La aparición de la inmuno-quimioterapia como alternativa de tratamiento tales como: inmuno quimioterapia con interferon-gamma y terapia multiple (MTD), ANTIBIÓTICOS y terapia multiple, vacunas y MTD.
6.) Existen 2 vacunas inmunoterapeuticas para la lepra:
A.) Una de ellas basadas en el Mycobacterium w. La vacuna Mycobacterium w (Mw) es una suspensión derivada de una micobacteria atípica cultivable no patógena llamada Mycobacterium indicus pranii (MIP). Se ha informado que la inmunoterapia con Mw es eficaz como complemento del tratamiento multibacilar de múltiples fármacos en pacientes con lepra DESARROLLADA EN LA INDIA.
B.) La otra una combinación del Bacilo de Calmette Guerin (BCG), mas bacilos muertos de Mycobacterium Leprae, DESARROLLADA EN VENEZUELA. Los Hindúes descartaron esta "inmunoterapia al comprobar su inefectividad".
Ambas REALMENTE representan UNA INMUNOTERAPIA, y aunque han sido de gran utilidad, no garantizan la desaparición de la LEPRA.
7.) La aparición de nuevas técnicas diagnósticas (PCR) para observar el comportamiento y pronóstico de la enfermedad, que ayudan a las viejas tales como Mitsuda, Reacción de Fernández y CCB test, y genéticas que permitieron identificar el nuevo MYCOBACTERIUM LEPROMATOSIS.
8.) La comprobación de una susceptibilidad genética determinada por los antígenos de Histocompatibilidad (HLA) para adquirir o resistir la enfermedad.
9.) El éxito en reproducir la enfermedad en animales.
10.) El comprobado efecto protector del bacilo de Calmette Guerin (BCG) contra la lepra.
11.) La comprobación de transmisión de la lepra como enfermedad ZOONOTICA por el armadillo de 9 bandas (Dasypus novemcinctus) a humanos en Estados Unidos. El Armadillo de 9 bandas esta infectado naturalmente con el Mycobacterium Leprae.
12.) La Preservación del Mycobacterium leprae in vitro por 4 años por liofilización. El bacilo todavía no ha sido cultivado. Es un parásito intracelular obligatorio.
13.) Todavía en nuestros días el contacto con pacientes es el mayor determinante en la incidencia de lepra.
14.) La persistencia de la enfermedad en muchas áreas de nuestro mundo, a pesar
de los grandes esfuerzos y avances en su tratamiento.
15.) La enfermedad no se transmite con el embarazo, aun así ha sido descrita en niños menores de 2 meses de edad. (referencia 80).
Saludos a todos !!!
Dr. José Lapenta.
Many years have passed and many investigations have been made, Difficult treatment, ancestral and worldwide distribution mentioned in the Bible Which gives that apocalyptic touch to this dreaded disease, cause of social discrimination Even in our day.
It was ARMAUER HANSEN who discovered the bacillus that takes his name in the year Of 1.873, Bacillus of HANSEN, which is a Mycobacterium, called MYCOBACTERIUM LEPRAE. Since that moment the investigations have not stopped About this disease.
From the oil of Chalmoogra introduced by the Egyptian Tortoulis Bey in 1.894 to treat the disease until the manufacture of different vaccines (immunotherapy) Which are being used today, many years passed.
These 108 bibliographical references summarize many of the new Advances in the field of disease, new therapies, new findings But the disease remains "alive", has not been eradicated from the face of the earth.
That is the first thing I should report, although it is true that the cases have diminished By the effective work of the World Health Organization (WHO) at the World, and scientific advances HANSEN's disease still prevails In the world, in some regions more than others.
For the year 2015, 215.000 new cases of leprosy were reported in the Countries, with the largest number of cases in the INDIA with a 60%, other countries quite affected are BRAZIL and INDONESIA.
The "World Leprosy Day" is celebrated on the last Sunday in January of each year. It is a date to inform and raise public awareness about this disease.
It was promoted by the journalist Frances Raoul Follereau to help leprosy patients, and officially declared the first "World Day against Leprosy" on 31 January 1.954. Its objective was to raise awareness about the existence of this disease and to remove the negative image that was had of those affected.
THE ASPECTS TO HIGHLIGHT ARE:
1.) In the year 2.008 was discovered another MYCOBACTERIUM genetically different to LEPRAE, as agent Cause of leprosy, by the Department of Laboratory Medicine of the University of Texas, by Han and Collaborators, called MYCOBACTERIUM LEPROMATOSIS, a finding made in MEXICO, UNITED STATES and later SINGAPORE, INDIA and also found in the red squirrels of the BRITISH ISLANDS, which today are a reservoir for leprosy in these islands.
2.) Discovery of Resistance to MTD (Multi Drug Therapy) CLASIC treatment with
3.) The confirmation that antibiotics as OFLOXACIN, MINOCYCLINE, CLAVULANIC ACID plus AMOXICILLIN AND CLARITHROMYCIN are Highly bactericidal against Mycobacterium leprae, in fact MINOCYCLINE AND OFLOXACIN Today they are used in the treatment. The appearance of new drugs with antimycobacterial activity such as RIMINOPHENAZINES.
4.) The success of THALIDOMIDE to treat ERYTHEMA NODOSUM LEPROSUM (ENL), released to de market (again) IN THE UNITED STATES OF AMERICA since 1.998. Also the use of Antileukotrienes such as ZAFIRLUKAST to treat Leprous reaction, And new ones such as ETANERCEPT (Tumor Necrosis Factor Inhibitor).
5.) The appearance of immunochemotherapy as an alternative treatment Such as: immunochemotherapy with interferon-gamma and multiple therapy (MTD), ANTIBIOTICS and multiple therapy, vaccines and MTD.
6.) There are 2 immunotherapeutic vaccines for leprosy:
A.) Based on the Mycobacterium w. Mycobacterium w (Mw) vaccine is a suspension derived from an atypical non-pathogenic mycobacterium called Mycobacterium indicus pranii (MIP). Mw immunotherapy has been reported to be effective as a complement to multibacillary multidrug therapy in leprosy patients DEVELOPED IN THE INDIA.
B.) The other, a combination of Calmette Guerin Bacillus (BCG) plus dead Mycobacterium Leprae, DEVELOPED IN VENEZUELA. The Hindus ruled out this "immunotherapy after proving its ineffectiveness."
Both REALLY represent IMMUNOTHERAPY, and although they have been very useful, they do not guarantee the disappearance OF LEPRA.
7.) The appearance of new diagnostic techniques (PCR) to observe the Behavior and prognosis of the disease, which help the old Such as Mitsuda, Reaction of Fernandez and CCB test, and genetics that allowed Identify the new MYCOBACTERIUM LEPROMATOSIS.
8.) The verification of a genetic susceptibility determined by Histocompatibility Antigens (HLA) to acquire or resist the disease.
9.) The success in reproducing the disease in animals.
10.) The proven protective effect of Calmette Guerin's bacillus (BCG) Against leprosy.
11.) The verification of transmission of leprosy as a ZOONOTIC disease By the nine (9)-banded armadillo (Dasypus novemcinctus) to humans in the United States, The Nine-band Armadillo is naturally infected with Mycobacterium Leprae.
12.) Preservation of Mycobacterium leprae in vitro for 4 years by Lyophilization. The bacillus has not yet been cultivated. It is a parasite Intracellular.
13.) Still in our days, contact with patients is the greatest Determinant in the incidence of leprosy.
14.) The persistence of the disease in many areas of our world, despite Of the great efforts and advances in its treatment.
15.) The disease is not transmitted through pregnancy, even so it has been described in children less than 2 months of age. (Reference 80).
18,) The other use is in immunoprophylaxis, in order to protect a population at risk of acquiring the infection or disease. So far no vaccine against leprosy has been obtained; there are several candidates in development, but they are only experimental doses.
Here you will find the link to the update of this topic under the name LEPROSY AND VACCINES carried out in 2025
LET'S KEEP FIGHTING IT !!!
Greetings to all !!!
Dr. José Lapenta.
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2.) Localization of Mycobacterium leprae to endothelial cells of epineurial and perineurial blood vessels and lymphatics.
3.) Delayed-type hypersensitivity to Mycobacterium leprae soluble antigens as a test for infection with the leprosy bacillus.
4.) Detection of M. leprae by gene amplification; combined ethidium-bromide staining and probe hybridization.
5.) In vitro and in vivo activity of K-130, a dihydrofolate reductase inhibitor, against Mycobacterium leprae.
6.) Secreted proteins of Mycobacterium leprae.
7.) In vitro studies on extracellular matrix production by M.leprae infected murine neurofibroblasts.
8.) Opposite effects of M. leprae or M. bovis BCG delipidation on cellular accumulation into mouse pleural cavity. Distinct accomplishment of mycobacterial lipids in vivo.
9.) Role of alpha-dystroglycan as a Schwann cell receptor for Mycobacterium leprae [see comments]
10.) Human T cell recognition of the Mycobacterium leprae LSR antigen: epitopes and HLA restriction.
11.) A Mycobacterium leprae-specific human T cell epitope cross-reactive with an HLA-DR2 peptide.
12.) Association of HLA antigens with differential responsiveness to Mycobacterium w vaccine in multibacillary leprosy patients.
13.) HLA antigens and neural reversal reactions in Ethiopian borderline tuberculoid leprosy patients.
14.) Evidence for an HLA-DR4-associated immune-response gene for Mycobacterium tuberculosis. A clue to the pathogenesis of rheumatoid arthritis?
15.) Species-specific identification of Mycobacterium leprae by PCR-restriction fragment length polymorphism analysis of the hsp65 gene.
16.) Use of a whole blood assay to evaluate in vitro T cell responses to new leprosy skin test antigens in leprosy patients and healthy subjects.
17.) Relapse of leprosy after multidrug therapy.
18.) Leprosy resistant to multi-drug-therapy (MDT) successfully treated with ampicillin-sulbactam combination--(a case report).
19.) Specificity and function of immunogenic peptides from the 35-kilodalton protein of Mycobacterium leprae.
20.) [Morphological features to be considered as the growth of Mycobacterium leprae Thai-53 strain on a silicon coated slide in a cell-free liquid medium]
21.) Leprosy patients with lepromatous disease recognize cross-reactive Tcell epitopes in the Mycobacterium leprae 10-kD antigen.
22.) Diaminodiphenylsulfone resistance of Mycobacterium leprae due to mutations in the
dihydropteroate synthase gene.
23.) In vitro activity of epiroprim, a dihydrofolate reductase inhibitor, singly and in combination with brodimoprim and dapsone, against Mycobacterium leprae.
24.) Lymphoproliferative responses of leprosy patients and healthy controls to nitrocellulose-bound M. leprae antigens.
25.) Dominant recognition of a cross-reactive B-cell epitope in Mycobacterium leprae 10 K antigen by immunoglobulin G1 antibodies across the disease spectrum in leprosy.
26.) Immune responses to recombinant proteins of Mycobacterium leprae.
27.) Causative organism and host response. International Leprosy Congress,
28.) Immunohistological analysis of in situ expression of mycobacterial antigensin skin lesions of leprosy patients across the histopathological spectrum. Association of Mycobacterial lipoarabinomannan (LAM) and Mycobacterium leprae phenolic glycolipid-I (PGL-I) with leprosy reactions.
29.) IL-18 promotes type 1 cytokine production from NK cells and T cells in human intracellular infection.
30.) Identification of M.leprae in conjunctiva of leprosy patients using the superior tarsal conjunctiva scrape technique.
31.) [Present situation of leprosy in highly endemic area of tropical Asia--a seroepidemiological study of Mycobacterium leprae infection in general inhabitants]
32.) Anti M. leprae IgM antibody determination by ultramicroimmunoenzymatic (UMELISA HANSEN) for the diagnosis and monitoring leprosy.
33.) Opposite cellular accumulation and nitric oxide production in vivo after pleural immunization with M. leprae or M. bovis BCG.
34.) Use of a whole blood assay to monitor the immune response to mycobacterial antigens in leprosy patients: a predictor for type 1 reaction onset?
35.) A clinical and bacteriological examination of Mycobacterium leprae in the epidermis and cutaneous appendages of patients with multibacillary leprosy.
36.) Quality control tests for vaccines in leprosy vaccine trial, Avadi.
37.) Comparative leprosy vaccine trial in south India.
38.) Evolutionary bottlenecks in the agents of tuberculosis, leprosy, and paratuberculosis.
39.) Role of S-100 staining in differentiating leprosy from other granulomatous diseases of the skin.
40.) Assessment of anti-PGL-I as a prognostic marker of leprosy reaction.
41.) Conjunctival biopsy in patients with leprosy.
42.) Experimental leprosy in rhesus monkeys: transmission, susceptibility,clinical and immunological findings.
43.) Lepromatous uveitis diagnosed by iris biopsy.
44.) Preservation of Mycobacterium leprae in vitro for four years by lyophilization.
45.) Minocycline in lepromatous leprosy.
46.) Efficacy of minocycline in single dose and at 100 mg twice daily for lepromatous leprosy.
47.) Field trial on efficacy of supervised monthly dose of 600 mg rifampin, 400 mg ofloxacin and 100 mg minocycline for the treatment of leprosy; first results.
48.) Bactericidal activity of a single-dose combination of ofloxacin plus minocycline, with
or without rifampin, against Mycobacterium leprae in mice and in lepromatous patients.
49.) Efficacy of single dose multidrug therapy for the treatment of single-lesion
paucibacillary leprosy. Single-lesion Multicentre Trial Group.
50.) Bactericidal activity of single dose of clarithromycin plus
minocycline, with or without ofloxacin, against Mycobacterium leprae in patients.
51.) WHO Expert Committee on Leprosy.
52.) Experimental evaluation of possible new short-term drug regimens for
treatment of multibacillary leprosy.
53.) Powerful bactericidal activities of clarithromycin and minocycline
against Mycobacterium leprae in lepromatous leprosy.
54.) Differential protective effect of bacillus calmette-guerin vaccineagainst multibacillary
and paucibacillary leprosy in nagpur, india.
55.) An immunotherapeutic vaccine for multibacillary leprosy.
56.) Protective effect of Bacillus Calmette Guerin (BCG) against leprosy: a population-based case-control study in Nagpur, India.
57.) The antigen 85 complex vaccine against experimental Mycobacterium leprae infection in mice.
58.) Induction of lepromin positivity following immuno-chemotherapy with Mycobacterium w vaccine and multidrug therapy and its impact on bacteriological clearance in multibacillary leprosy: report on a hospital-based clinical trial with the candidate antileprosy vaccine.
59.) Disabilities in multibacillary leprosy following multidrug therapy with and without immunotherapy with Mycobacterium w antileprosy vaccine.
60.) SIMLEP: a simulation model for leprosy transmission and control.
61.) Antigenic definition of plasma membrane proteins of Bacillus Calmette-Guerin:
predominant activation of human T cells by low-molecular-mass integral proteins.
62.) A lost talisman: catastrophic decline in yields of leprosy bacilli from armadillos used for vaccine production.
63.) HLA-DRB1 leprogenic motifs in nigerian population groups.
64.) Testing candidate genes that may affect susceptibility to leprosy.
65.) [Leprosy, an "exemplary" humanitarian disease]?
66.) Prediction of elimination of leprosy in leprosy endemic areas of China.
67.)[Global leprosy, current status and a future outlook].
68.) Lot quality assurance sampling (LQAS) for monitoring a leprosy elimination program.
69.) Patient contact is the major determinant in incident leprosy: implications for future control.
70.) A continuing focus of Hansen's disease in Texas.
71.) An epidemiological study on Mycobacterium leprae infection and prevalence of leprosy in endemic villages by molecular biological technique.
72.) Antimycobacterial activities of riminophenazines.
73.) Nasal mucosa and skin of smear-positive leprosy patients after 24 months of fixed duration MDT: histopathological and microbiological study.
74.) Resolution of lepromatous leprosy after a short course of amoxicillin/clavulanic acid,
followed by ofloxacin and clofazimine.
75.) Effect of zafirlukast on leprosy reactions.
76.) Immunochemotherapy with interferon-gamma and multidrug therapy for multibacillary leprosy.
77.) Thalidomide's effectiveness in erythema nodosum leprosum is associated with a decrease in CD4+ cells in the peripheral blood.
78.) La lepra, Evolucion Historia, epidemiologica y medidas de control.
79.) Leprosy in infants.
80.) Leprosy in a child of less than two months of age.
81.) Spatial clustering and local risk of leprosy in São Paulo, Brazil.
82.) Unexpectedly high leprosy seroprevalence detected using a random surveillance strategy in midwestern Brazil: A comparison of ELISA and a rapid diagnostic test.
83.) Cojedes: a leprosy hyperendemic state. (VENEZUELA)
84.) Seguimiento serológico de las respuestas de IgG frente a proteínas micobacterianas recombinantes ML0405, ML2331 y LID-1 en un área hiperendémica de lepra en Venezuela.
Portuguesa state (VENEZUELA).
85.) [A socioeconomic characterization of leprosy patients at the dermatology clinic in Maracaibo, VENEZUELA: a case study]
86.) [The current challenge of imported leprosy in Spain: a study of 7 cases].
87.) Leprosy trends at a tertiary care hospital in Mumbai, India, from 2008 to 2015.
88.) Childhood leprosy: a retrospective descriptive study from Government Medical College, Kozhikode, Kerala, India.
89.) "I Wasted 3 Years, Thinking It's Not a Problem": Patient and Health System Delays in Diagnosis of Leprosy in India: A Mixed-Methods Study.
90.) Minocycline successfully treats exaggerated granulomatous hypersensitivity reaction to Mw immunotherapy.
91.) Generalized granulomatous dermatitis following Mycobacterium w (Mw) immunotherapy in lepromatous leprosy.
92.) World Leprosy Day
93.) Mutations in the drug resistance-determining region of Mycobacterium lepromatosis isolated from leprosy patients in Mexico.
94.) Red squirrels in the British Isles are infected with leprosy bacilli.
95.) Unsolved matters in leprosy: a descriptive review and call for further research.
96.) Delayed Diagnosis, Leprosy Reactions, and Nerve Injury Among Individuals With Hansen's Disease Seen at a United States Clinic.
97.) The leprosy agents Mycobacterium lepromatosis and Mycobacterium leprae in Mexico.
98.) Identification of the leprosy agent Mycobacterium lepromatosis in Singapore.
99.) A new Mycobacterium species causing diffuse lepromatous leprosy.
100.) Zoonotic Leprosy in the Southeastern United States.
101.) Borderline tuberculoid leprosy in a woman from the state of Georgia with armadillo exposure.
102.) Minocycline in leprosy patients with recent onset clinical nerve function impairment.
103.) Leprosy Drug Resistance Surveillance in Colombia: The Experience of a Sentinel Country.
104.) Drug resistance in Mycobacterium leprae from patients with leprosy in China.
105.) [Study of rifampin and dapsone resistance in three patients with recurring leprosy].
106.) Possible mode of emergence for drug-resistant leprosy is revealed by an analysis of samples from Mexico.
107.) What is the evidence that the putative Mycobacterium lepromatosis species causes diffuse lepromatous leprosy?
108.) Treatment of severe refractory erythema nodosum leprosum with tumor necrosis factor inhibitor Etanercept.
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1.) A 21-kDa surface protein of Mycobacterium leprae binds peripheral nerve laminin-2 and mediates Schwann cell invasion.
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Address
Laboratory of Bacterial Pathogenesis and Immunology, The Rockefeller
University, New York, NY 10021, USA.
Source
Proc Natl Acad Sci U S A, 96(17):9857-62 1999 Aug 17
Abstract
Nerve damage is the hallmark of Mycobacterium leprae infection, which results from M. leprae invasion of the Schwann cell of the peripheral nervous system. We have recently shown that the laminin-2 isoform, specially the G domain of laminin alpha2 chain, on the Schwann cell-axon unit serves as an initial neural target for M. leprae. However, M. leprae surface molecules that mediate bacterial invasion of peripheral nerves are entirely unknown. By using human alpha2 laminins as a probe, a major 28-kDa protein in the M. leprae cell wall fraction that binds alpha2 laminins was identified. After N-terminal amino acid sequence analysis, PCR-based strategy was used to clone the gene that encodes this protein. Deduced amino acid sequence of this M. leprae laminin-binding protein predicts a 21-kDa molecule (ML-LBP21), which is smaller than the observed molecular size in SDS/PAGE. Immunofluorescence and immunoelectron microscopy on intact M. leprae with mAbs against recombinant (r) ML-LBP21 revealed that the protein is surface exposed. rML-LBP21 avidly bound to alpha2 laminins, the rG domain of the laminin-alpha2 chain, and the native peripheral nerve laminin-2. The role of ML-LBP21 in Schwann cell adhesion and invasion was investigated by using fluorescent polystyrene beads coated with rML-LBP21. Although beads coated with rML-LBP21 alone specifically adhered to and were ingested by primary Schwann cells, these functions were significantly enhanced when beads were preincubated with exogenous alpha2 laminins. Taken together, the present data suggest that ML-LBP21 may function as a critical surface adhesin that facilitates the entry of M. leprae into Schwann cells.
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2.) Localization of Mycobacterium leprae to endothelial cells of epineurial and perineurial blood vessels and lymphatics.
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Author
Scollard DM; McCormick G; Allen JL
Address
Department of Research Pathology, G. W. L. Hansen's Disease
Center at Louisiana State University, Baton Rouge, LA, USA.
dscoll1@lsu.edu
Source
Am J Pathol, 154(5):1611-20 1999 May Abstract Infection of
peripheral nerve by Mycobacterium leprae, the histopathological
hallmark of leprosy, is a major factor in this disease, but the
route and mechanisms by which bacilli localize to peripheral
nerve are unknown. Experimentally infected armadillos have
recently been recognized as a model of lepromatous neuritis; the
major site of early accumulation of M. leprae is epineurial. To
determine the epineurial cells involved, 1-cm segments of 44
nerves from armadillos were screened for acid-fast bacilli and
thin sections were examined ultrastructurally. Of 596 blocks
containing nerve, 36% contained acid-fast bacilli. Overall, M.
leprae were found in endothelial cells in 40% of epineurial
blood vessels and 75% of lymphatics, and in 25% of vessels
intraneurally. Comparison of epineurial and endoneurial findings
suggested that colonization of epineurial vessels preceded
endoneurial infection. Such colonization of epineurial nutrient
vessels may greatly increase the risk of endoneurial M. leprae
bacteremia, and also enhance the risk of ischemia following even
mild increases in inflammation or mechanical stress. These
findings also raise the possibility that early, specific
mechanisms in the localization of M. leprae to peripheral nerve
may involve adhesion events between M. leprae (or M.
leprae-parasitized macrophages) and the endothelial cells of the
vasa nervorum.
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3.) Delayed-type hypersensitivity to Mycobacterium leprae soluble antigens as a test for infection with the leprosy bacillus.
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Author
Sterne JA; Fine PE; P¨onnighaus JM; Rees RJ; Chavula D
Address
Department of Public Health Medicine, United Medical and Dental Schools of Guy's and St Thomas's Hospitals, London, UK.
Source
Int J Epidemiol, 27(4):713-21 1998 Aug
Abstract
BACKGROUND: Mycobacterium leprae (M. leprae) soluble antigen (MLSA) reagents have been developed with the aim of finding a reagent, comparable to tuberculin, which could identify individuals infected with the leprosy bacillus. They have yet to be evaluated fully in human populations. METHODS: More than 15000 individuals living in a leprosy endemic area of northern Malawi were skin tested with one of five batches of MLSA prepared using two different protocols. The main difference in preparation was the introduction of a high G centrifugation step in the preparation of the last three ('second-generation') batches. RESULTS: The prevalence of skin-test positivity (delayed-type hypersensitivity (DTH)) and association with the presence of a BCG scar were greater for first (batches A6, A22) than second (batches AB53, CD5, CD19) generation reagents. The association of positivity with M. leprae infection was investigated by comparing results among known (household) contacts of leprosy cases, and among newly diagnosed leprosy patients with those in the general population. While positivity to 'first-generation' antigens appeared to be associated with M. leprae infection, positivity to later antigens was unrelated either to exposure to leprosy cases or presence of leprosy disease. There were geographical differences in the prevalence of DTH to the various batches, probably reflecting exposure to various mycobacteria in the environment. CONCLUSIONS: Our results suggest that the 'second-generation' batches have lost antigens that can detect M. leprae infections, but that they retain one or more antigens which are shared between M. leprae and environmental mycobacteria. Natural exposure to these both sensitizes individuals and provides natural protection against M. leprae infection or disease. Identification of antigens present in these groups of skin test reagents may assist in production of improved skin test reagents.
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4.) Detection of M. leprae by gene amplification; combined ethidium-bromide staining and probe hybridization.
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Sharma RK; Katoch K; Shivannavar CT; Sharma VD; Natrajan M; Bhatia AS;
Saxena N;
Katoch VM
Central JALMA Institute for Leprosy (ICMR), Taj Ganj, Agra, India.
Int J Lepr Other Mycobact Dis (UNITED STATES) Dec 1996 64 (4) p409-16
ISSN:
0148-916X
Language: ENGLISH
Document Type: JOURNAL ARTICLE
Journal Announcement: 9705
Subfile: INDEX MEDICUS
Biopsy and skin-scraping specimens from 130 leprosy cases across the disease spectrum (56 TT/BT/I, 73 BB/BL/LL, and 1 neuritic case) and 50 healthy contacts were studied to assess the application of gene amplification. The nucleic acids from these clinical specimens were extracted by an integrated freeze-thawing-optimized lysozyme-/proteinase-k treatment-purification and fractionation procedure. The nucleic acids from cultured organisms were isolated by the stepwise procedure earlier standardized at this laboratory. Gene amplification for a 360-bp fragment of the 18-kDa protein gene was carried out using primer and the procedure described by its developers, and a 360-bp fragment on Southern blot was taken as the yardstick of positivity. The polymerase chain reaction product was analyzed by electrophoresis, ethidium-bromide (EB) staining, and blot (B) hybridization. Overall sensitivity ranged from 71% in specimens with undetectable acid-fast organisms to 100% in specimens with demonstrable acid-fast bacilli. A positivity of 73% in TT/BT/I specimens and 93% in BB/BL/LL specimens was observed. Four combinations were discerned: EB+, B+ (71%); EB-suspicious, B+ (14%); EB-, B+ (3%) and EB-, B- (12%). By combining the blot hybridization with EB staining, the sensitivity could be significantly improved as compared to EB staining alone. The test was found to be absolutely specific by the absence of any false positivity in control specimens as well as with purified DNAs from mycobacterial as well as non-mycobacterial organisms, grown from these specimens. It is recommended that for optimum sensitivity and specificity both EB staining and blot hybridization should be done.
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5.) In vitro and in vivo activity of K-130, a dihydrofolate reductase
inhibitor, against Mycobacterium leprae.
============================================================
Author
Dhople AM
Address
Florida Institute of Technology, Department of Biological Sciences,
Melbourne, USA.
Source
Arzneimittelforschung, 49(3):267-71 1999 Mar
Abstract
The antimicrobial effects of a new dihydrofolate reductase inhibitor,
K-130 (2,4-diaminodiphenyl sulfone substituted
2,4-diamino-5-benzylpyrimidine), alone and in combination with dapsone
(CAS 80-08-0) against both dapsone-sensitive and dapsone-resistant strains
of Mycobacterium leprae were evaluated in vitro, in cell-free culture
system, and in vivo, in mouse foot pads. The minimal inhibitory
concentration of K-130 against dapsone-sensitive as well as dapsone
resistant strains of M, leprae was 0.03 microgram/ml, and the activity was
bactericidal in both cases. However, when combined with dapsone, K-130
exhibited synergism in case of dapsone-sensitive M. leprae, while in case
of dapsone-resistant M. leprae, the effect was merely additive. Similar
synergistic effects were also observed in the mouse foot pad system for
both types of M. leprae strains.
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6.) Secreted proteins of Mycobacterium leprae.
============================================================
Author
Harboe M; Wiker HG
Address
Institute of Immunology and Rheumatology, University of Oslo, Norway.
Source
Scand J Immunol, 48(6):577-84 1998 Dec
Abstract
In mycobacteria, secreted proteins represent a distinct group, probably of
particular importance for development of immune responses following
infection. Quantification of individual proteins in culture fluid and
corresponding disrupted bacilli permits determination of a localization
index for identification of secreted proteins. This procedure cannot be
applied to Mycobacterium leprae because secreted proteins are lost during
isolation of bacilli from tissues. The DNA sequences of secreted proteins
of Mycobacterium tuberculosis were compared with sequences of M. leprae.
Genes for homologues of the 85a, 85b, 85c, mpt32 (apa), mpt51, erp, mtc28,
Rv2376c, Rv3354 and Rv0526 genes were identified. All of these contain
signal sequences typical for secretion in M. leprae. In several instances
the local distance between marker genes and occurrence on the same or the
complementary DNA strand was similar in these two species. The genomic
organisation of genes for secreted proteins is thus very similar in M.
leprae and M. tuberculosis, the homology being higher for the mature
polypeptide chains than for the corresponding signal peptides.
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7.) In vitro studies on extracellular matrix production by M.leprae
infected murine neurofibroblasts.
============================================================
Author
Singh N; Birdi TJ; Chandrashekar S; Antia NH
Address
Foundation for Medical Research, R.G. Thadani Marg, Bombay, India.
Source
Lepr Rev, 69(3):246-56 1998 Sep
Abstract
Fibroblasts and a host of macrophage secretory products have been
implicated in a number of diseases where excess extracellular matrix (ECM)
deposition is the main pathological feature. Fibrosis characterized by
excessive deposition of collagen also contributes to the irreversible
nerve damage observed in leprosy. Since M. leprae are seen within
neurofibroblasts (Nf) in the advanced stages of the disease and
macrophages form a common infiltrating cellular constituent of leprous
nerves at all stages, secretion of ECM proteins by Nf was studied, in
vitro following infection with M. leprae and in the presence of macrophage
secretory products. These studies were compared in cells derived from two
strains of mice, Swiss White (SW) and C57BL/6, as they differ in their
response to M. leprae infection and parallel those observed in lepromatous
and tuberculoid patients, respectively. On infection with M. leprae, Nfs
showed a decrease in secretion of collagen type IV in SW and type I in
C57Bl/6 strain. Macrophages caused a further decrease in the secretion of
collagen types affected by M. leprae infection per se, while the other
collagen types, viz. I and III in SW strain and III and IV in C57Bl/s
strain, were unaffected. This study indicates that neural collagenization
in nerves in advanced leprosy may be of Nf origin. However, unlike other
diseases with excess collagen deposition, ECM proteins produced by Nfs in
response to nerve damage may not be of prime importance in the progression
of leprous neuropathy and occur as a general response to loss of cellular
content in leprous nerves.
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8.) Opposite effects of M. leprae or M. bovis BCG delipidation on cellular
accumulation into mouse pleural cavity. Distinct accomplishment of
mycobacterial lipids in vivo.
============================================================
Author
Moura AC; Leonardo PS; Henriques MG; Cordeiro RS
Address
Departmento de Biologia Celular e Gen´etica, Instituto de Biologia,
Universidade do Rio de Janeiro, Brazil. cmoura@uerj.br
Source
Inflamm Res, 48(6):308-13 1999 Jun
Abstract
OBJECTIVES AND DESIGN: The effect of mycobacterial lipids on the onset of
the early acute inflammatory response in BALB/c mice pleurisy was
investigated. MATERIALS AND METHODS: Intact Mycobacterium leprae and
Mycobacterium bovis BCG (BCG), their lipids, and delipidated mycobacteria
were used to evaluate total leukocytes and cell types migrated to the
pleural cavity (8 animals/experimental group). RESULTS: BCG Moreau
(x10(-6)/cavity), delipidated BCG and its lipids gradually recruited cells
leading to arrival, respectively, of neutrophils (7.8+/-1.9, 4.7+/-0.9,
1.8+/-0.25) followed by mononuclear cells (4.8+/-0.8, 3.7+/-0.7,
2.45+/-0.22) and eosinophils (0.39+/-0.08, 0.32+/-0.11, 0.41+/-0.65). BCG
delipidation decreased the number of migrated total leukocytes (ANOVA, and
Newman-Keuls-Student-test), whereas M. leprae delipidation accumulated
neutrophils (0.85+/-0.01) and eosinophils (1.65+/-0.18). CONCLUSIONS:
Intact M. leprae and its lipids did not incite any cell recruitment.
Apolar external cell wall lipids from M. leprae and BCG induce different
cellular responses. They seem to have a crucial importance at the first
contact of mycobacteria with the host cell, modulating the influx of
neutrophils/macrophages in the early (4/24 h) onset of the inflammatory
reaction.
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9.) Role of alpha-dystroglycan as a Schwann cell receptor for
Mycobacterium leprae [see comments]
============================================================
Author
Rambukkana A; Yamada H; Zanazzi G; Mathus T; Salzer JL; Yurchenco PD;
Campbell KP; Fischetti VA
Address
Laboratory of Bacterial Pathogenesis and Immunology, Rockefeller
University, New York, NY 10021, USA. rambuka@rockvax.rockefeller.edu
Source
Science, 282(5396):2076-9 1998 Dec 11
Abstract
alpha-Dystroglycan (alpha-DG) is a component of the dystroglycan complex,
which is involved in early development and morphogenesis and in the
pathogenesis of muscular dystrophies. Here, alpha-DG was shown to serve as
a Schwann cell receptor for Mycobacterium leprae, the causative organism
of leprosy. Mycobacterium leprae specifically bound to alpha-DG only in
the presence of the G domain of the alpha2 chain of laminin-2. Native
alpha-DG competitively inhibited the laminin-2-mediated M. leprae binding
to primary Schwann cells. Thus, M. leprae may use linkage between the
extracellular matrix and cytoskeleton through laminin-2 and alpha-DG for
its interaction with Schwann cells.
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10.) Human T cell recognition of the Mycobacterium leprae LSR antigen:
epitopes and HLA restriction.
============================================================
Author
Oftung F; Lundin KE; Meloen R; Mustafa AS
Address
Department of Vaccinology, National Institute of Public Health, Oslo,
Norway. frederik.oftung@folkehelsa.no
Source
FEMS Immunol Med Microbiol, 24(2):151-9 1999 Jun
Abstract
We have in this work mapped epitopes and HLA molecules used in human T
cell recognition of the Mycobacterium leprae LSR protein antigen. HLA
typed healthy subjects immunized with heat killed M. leprae were used as
donors to establish antigen reactive CD4+ T cell lines which were screened
for proliferative responses against overlapping synthetic peptides
covering the C-terminal part of the antigen sequence. By using this
approach we were able to identify two epitope regions represented by
peptide 2 (aa 29-40) and peptide 6 (aa 49-60), of which the former was
mapped in detail by defining the N- and C-terminal amino acid positions
necessary for T cell recognition of the core epitope. MHC restriction
analysis showed that peptide 2 was presented to T cells by allogeneic
cells coexpressing HLA-DR4 and DRw53 or DR7 and DRw53. In contrast,
peptide 6 was presented to T cells only in the context of HLA-DR5
molecules. In conclusion, the M. leprae LSR protein antigen can be
recognized by human T cells in the context of multiple HLA-DR molecules,
of which none are reported to be associated with the susceptibility to
develop leprosy. The results obtained are in support of using the LSR
antigen in subunit vaccine design.
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11.) A Mycobacterium leprae-specific human T cell epitope cross-reactive
with an HLA-DR2 peptide.
============================================================
ARTICLE SOURCE: Science (United States), Oct 14 1988, 242(4876) p259-61
AUTHOR(S): Anderson DC; van Schooten WC; Barry ME; Janson AA; Buchanan
TM;
de Vries RR
PUBLICATION TYPE: JOURNAL ARTICLE
ABSTRACT: Mycobacterium leprae induces T cell reactivity and protective
immunity in the majority of exposed individuals, but the minority that
develop leprosy exhibit various types of immunopathology. Thus, the
definition of epitopes on M. leprae antigens that are recognized by T
cells from different individuals might result in the development of an
effective vaccine against leprosy. A sequence from the 65-kD protein of
this organism was recognized by two HLA-DR2-restricted, M. leprae-specific
helper T cell clones that were derived from a tuberculoid leprosy patient.
Synthetic peptides were used to define this epitope as
Leu-Gln-Ala-Ala-Pro-Ala-Leu-Asp-Lys-Leu. A similar peptide that was
derived from the third hypervariable region of the HLA-DR2 chain,
Glu-Gln-Ala-Arg-Ala-Ala-Val-Asp-Thr-Tyr, also activated the same clones.
The unexpected cross-reactivity of this M. leprae-specific DR2-restricted
T cell epitope with a DR2 peptide may have to be considered in the design
of subunit
============================================================
12.) Association of HLA antigens with differential responsiveness to
Mycobacterium w vaccine in multibacillary leprosy patients.
============================================================
ARTICLE SOURCE: J Clin Immunol (United States), Jan 1992, 12(1) p50-5
AUTHOR(S): Rani R; Zaheer SA; Suresh NR; Walia R; Parida SK; Mukherjee A;
Mukherjee R; Talwar GP
PUBLICATION TYPE: JOURNAL ARTICLE
ABSTRACT: Leprosy patients undergoing phase II trials in two hospitals of
New Delhi, India, were HLA typed to see the association of HLA with
differential responsiveness to Mycobacterium w vaccine. The vaccine
comprises an atypical, nonpathogenic mycobacterium, Mycobacterium w, which
has cross-reactive antigens with M. leprae. Multibacillary patients who
are lepromin negative are vaccinated at an interval of 3 months.
Considerable improvement is evident in the patients in terms of a decline
in bacterial indices and histopathological and immunological upgrading.
But all the patients do not respond to the vaccine in the same manner;
some are slow responders, while others are good responders. HLA-A28 and
DQw3 (DQw8 + 9) were found to be associated with slow responsiveness,
while DQw1 and DQw7 were found to be associated with a more rapid
responsiveness to the M. w vaccine. However, these associations were not
significant after P correction for the number of antigens tested for each
locus except for HLA-DQw3 (DQw8 and DQw9) and DQw7. DQw7, a new defined
split of HLA-DQw3, seems to be associated with the responsiveness to M. w
vaccine.
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13.) HLA antigens and neural reversal reactions in Ethiopian borderline
tuberculoid leprosy patients.
============================================================
ARTICLE SOURCE: Int J Lepr Other Mycobact Dis (United States), Jun 1987,
55(2) p261-6
AUTHOR(S): Ottenhoff TH; Converse PJ; Bjune G; de Vries RR
PUBLICATION TYPE: JOURNAL ARTICLE
ABSTRACT: Reversal reactions (RR) or acute neuritis episodes are
frequently observed in borderline tuberculoid (BT) leprosy patients during
the first year of treatment, and are associated with a rapid increase in
cell-mediated immunity. Because HLA-linked genes have been shown to be an
important factor in determining the type of leprosy that develops in
susceptible individuals and because HLA molecules regulate cellular
interactions in the immune system, we have investigated whether RR are
associated with HLA antigens in Ethiopian patients. The data reported here
indicate that this is not the case: no significant differences in the
distribution of HLA class I and class II antigens were observed among
three groups: 28 BT patients with a history of RR, 27 BT patients with no
history of RR, and 33 healthy individuals. In contrast to these negative
results, we observed that HLA-DR3 was associated with high skin-test
responsiveness against Mycobacterium leprae antigens among RR patients.
Since DR3 was not associated with RR per se, the observed DR3-associated
high responsiveness to M. leprae may not be primarily
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14.) Evidence for an HLA-DR4-associated immune-response gene for
Mycobacterium tuberculosis. A clue to the pathogenesis of rheumatoid
arthritis?
============================================================
ARTICLE SOURCE: Lancet (England), Aug 9 1986, 2(8502) p310-3
AUTHOR(S): Ottenhoff TH; Torres P; de las Aguas JT; Fernandez R; van Eden
W; de Vries RR; Stanford JL
PUBLICATION TYPE: JOURNAL ARTICLE
ABSTRACT: Antigens of Mycobacterium tuberculosis, M leprae, M
scrofulaceum, and M vaccae were injected intradermally in 86 caucasoid
leprosy patients, and skin responses (measured in mm of induration at 72
h) were analysed in relation to HLA class II phenotypes. HLA-DR4 was
associated with high responsiveness to antigens specific to M tuberculosis
but not to antigens shared with other mycobacteria (p = 0.0005). Because
DR4 is associated with rheumatoid arthritis (RA) and because a role for M
tuberculosis antigens has been suggested both in experimentally induced
autoimmune arthritis in rats and in RA, the DR4 associated regulation of
the immune response to M tuberculosis may be relevant to the pathogenesis
of RA.
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15.) Species-specific identification of Mycobacterium leprae by
PCR-restriction fragment length polymorphism analysis of the hsp65 gene.
============================================================
Author
Rastogi N; Goh KS; Berchel M
Address
Unit´e de la Tuberculose et des Mycobact´eries, Institut Pasteur, 97165
Pointe `a Pitre Cedex, Guadeloupe. rastogi@ipagua.gp
Source
J Clin Microbiol, 37(6):2016-9 1999 Jun
Abstract
PCR-restriction fragment length polymorphism analysis (PRA) of the hsp65
gene present in all mycobacteria was used in the present investigation to
characterize Mycobacterium leprae. Bacilli were extracted and purified
from different organs from experimentally infected armadillos and nude
mice (Swiss mice of nu/nu origin). A total of 15 samples were assayed in
duplicate, and the results were compared with those obtained for a total
of 147 cultivable mycobacteria representing 34 species. Irrespective of
its origin or viability, M. leprae strains from all the samples were
uniformly characterized by two fragments of 315 and 135 bp upon BstEII
digestion and two fragments of 265 and 130 bp upon HaeIII digestion. PRA
is a relatively simple method and permits the conclusive identification of
M. leprae to the species level.
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16.) Use of a whole blood assay to evaluate in vitro T cell responses to
new leprosy skin test antigens in leprosy patients and healthy subjects.
============================================================
Author
Weir RE; Brennan PJ; Butlin CR; Dockrell HM
Address
Department of Infectious and Tropical Diseases, London School of Hygiene
&
Tropical Medicine, London, UK. r.weir@lshtm.ac.uk
Source
Clin Exp Immunol, 116(2):263-9 1999 May
Abstract
Development of an immunological tool to detect infection with
Mycobacterium leprae would greatly benefit leprosy control programmes, as
demonstrated by the contribution of the tuberculin test to tuberculosis
control. In a new approach to develop a 'tuberculin-like' reagent for use
in leprosy, two new fractions of M. leprae depleted of cross-reactive and
immunomodulatory lipids- MLSA-LAM (cytosol-derived) and MLCwA (cell
wall-derived)-have been produced in a form suitable for use as skin test
reagents. T cell responses (interferon-gamma (IFN-gamma) and
lymphoproliferation) to these two new fractions were evaluated in a
leprosy-endemic area of Nepal using a simple in vitro whole blood test.
The two fractions were shown to be highly potent T cell antigens in
subjects exposed to M. leprae-paucibacillary leprosy patients and
household contacts. Responses to the fractions decreased towards the
lepromatous pole of leprosy. Endemic control subjects also showed high
responses to the fractions, indicating high exposure to M. leprae, or
cross-reactive mycobacterial antigens, in this Nepali population. The new
fractions, depleted of lipids and lipoarabinomannan (LAM) gave enhanced
responses compared with a standard M. leprae sonicate. The cell wall
fraction appeared a more potent antigen than the cytosol fraction, which
may be due to the predominance of the 65-kD GroEL antigen in the cell
wall. The whole blood assay proved a robust field tool and a useful way of
evaluating such reagents prior to clinical trials.
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17.) Relapse of leprosy after multidrug therapy.
============================================================
Dasananjali K
Department of Communicable Disease Control, Ministry of Public Health,
Nonthaburi,
Thailand.
J Med Assoc Thai (THAILAND) Oct 1996 79 (10) p635-9 ISSN: 0125-2208
Language: ENGLISH
Document Type: JOURNAL ARTICLE
Journal Announcement: 9704
Subfile: INDEX MEDICUS
Relapse of leprosy after multidrug therapy among leprosy patients treated
at Mahasarakarm, Kalasin and Roi-et from 1984 to 1994 were analyzed.
Twenty PB relapses (45.45%) and twenty four MB relapses (54.55%) were
found among 5,298 originally classified PB patients and 5 MB relapses
occurred in 2,624 originally classified MB patients. Mean relapse interval
was between 3-4 years. The relapse rate within 10 years after stopping MDT
was 0.83 per cent in PB and 0.19 per cent in MB. The estimated relapse
rate per 1,000 patient-years was 1.55 for PB and 0.41 for MB respectively.
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18.) Leprosy resistant to multi-drug-therapy (MDT) successfully treated
with ampicillin-sulbactam combination--(a case report).
============================================================
Mehta VR
L.T.M.M. College, Bombay.
Indian J Med Sci (INDIA) Nov 1996 50 (11) p305-7 ISSN: 0019-5359
Language: ENGLISH
Document Type: JOURNAL ARTICLE
Journal Announcement: 9707
Subfile: INDEX MEDICUS
A 50 year male developed a discoid lesion of leprosy on the face. Inspite
of Dapsone 100 mg/day and Rifampicin 600 mgm per day the disease spread to
both sides of the face and forehead. It became worse with Prednisolone and
Clofazimine. It cleared completely when Sultamicillin was added to the
latter. This seems to be the first patient of leprosy to be treated with
this combination and reported.
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19.) Specificity and function of immunogenic peptides from the
35-kilodalton protein of Mycobacterium leprae.
============================================================
Author
Wilkinson RJ; Wilkinson KA; Jurcevic S; Hills A; Sinha S; Sengupta U;
Lockwood DN; Katoch K; Altman D; Ivanyi J
Address
MRC Clinical Sciences Center, Imperial College School of Medicine,
Hammersmith Hospital, London W12 0NN, United Kingdom.
Source
Infect Immun, 67(3):1501-4 1999 Mar
Abstract
We identified a T-cell determinant of the 35-kDa antigen of Mycobacterium
leprae which is discriminatory against cross-sensitization by its closely
related homologue in Mycobacterium avium. From synthetic peptides covering
the entire sequence, those with the highest affinity and permissive
binding to purified HLA-DR molecules were evaluated for the stimulation of
proliferation of peripheral blood mononuclear cells (PBMCs) from leprosy
patients and healthy sensitized controls. Responses to the peptide pair
206-224, differing by four residues between M. leprae and M. avium,
involved both species-specific and cross-reactive T cells. Lymph node cell
proliferation in HLA-DRB1*01 transgenic mice was reciprocally species
specific, but only the response to the M. leprae peptide in the context of
DR1 was immunodominant. Of the cytokines in human PBMC cultures, gamma
interferon production was negligible, while interleukin 10 (IL-10)
responses in both patients and controls were more pronounced. IL-10 was
most frequently induced by the shared 241-255 peptide, indicating that
environmental cross-sensitization may skew the response toward a
potentially pathogenic cytokine phenotype.
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20.) [Morphological features to be considered as the growth of
Mycobacterium leprae Thai-53 strain on a silicon coated slide in a
cell-free liquid medium]
============================================================
Author
Nakamura M; Matsuoka M
Address
Koga Hospital Medical Research Institute, Kurume, Japan.
Source
Nihon Hansenbyo Gakkai Zasshi, 67(2):287-91 1998 Jul
Abstract
Morphological findings of the cells of Mycobacterium leprae Thai-53 strain
smeared on a silicon-coated slide cultured in Kirchner liquid medium pH
7.0, enriched with adenosine, egg yolk, folinic acid, vitamin K3,
lecithin, and N-acetylglucosamine at 30 degrees C were demonstrated. On
the basis of the results with exquisite morphological growth patterns and
the increase in the amount of tempelate DNA prepared from the cultured
cells, it is evident that the cells of M.leprae are capable of
multiplication under cell-free in vitro conditions. The reason why the ATP
content did not increase in parallel with morphological features and the
increase in the DNA is presumably that the multiplication of M.leprae in
this culture system was supported only by consuming the energy derived
from the infected host cells.
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21.) Leprosy patients with lepromatous disease recognize cross-reactive T
cell epitopes in the Mycobacterium leprae 10-kD antigen.
============================================================
Author
Hussain R; Dockrell HM; Shahid F; Zafar S; Chiang TJ
Address
Department of Microbiology, The Aga Khan University, Karachi, Pakistan.
Source
Clin Exp Immunol, 114(2):204-9 1998 Nov
Abstract
T cell responses play a critical role in determining protective responses
to leprosy. Patients with self-limiting tuberculoid leprosy show high T
cell reactivity, while patients with disseminated lepromatous form of the
disease show absent to low levels of T cell reactivity. Since the T cell
reactivity of lepromatous patients to purified protein derivative (PPD), a
highly cross-reactive antigen, is similar to that of tuberculoid patients,
we queried if lepromatous patients could recognize cross-reactive epitopes
in Mycobacterium leprae antigens as well. T cell responses were analysed
to a recombinant antigen 10-kD (a heat shock cognate protein) which is
available from both M. tuberculosis (MT) and M. leprae (ML) and displays
90% identity in its amino acid sequence. Lymphoproliferative responses
were assessed to ML and MT 10 kD in newly diagnosed leprosy patients
(lepromatous, n = 23; tuberculoid, n = 65). Lepromatous patients showed
similar, but low, lymphoproliferative responses to ML and MT 10 kD, while
tuberculoid patients showed much higher responses to ML 10 kD. This
suggests that the tuberculoid patients may be recognizing both
species-specific and cross-reactive epitopes in ML 10 kD, while
lepromatous patients may be recognizing only cross-reactive epitopes. This
was further supported by linear regression analysis. Lepromatous patients
showed a high concordance in T cell responses between ML and MT 10 kD
(r=0.658; P<0.0006) not observed in tuberculoid patients (r=0.203;
P>0.1). Identification of cross-reactive T cell epitopes in M. leprae
which could induce protective responses should prove valuable in designing
second generation peptide-based vaccines.
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22.) Diaminodiphenylsulfone resistance of Mycobacterium leprae due to
mutations in the dihydropteroate synthase gene.
============================================================
Author
Kai M; Matsuoka M; Nakata N; Maeda S; Gidoh M; Maeda Y; Hashimoto K;
Kobayashi K; Kashiwabara Y
Address
Leprosy Research Center, National Institute of Infectious Diseases, Tokyo,
Japan. mkai@nih.go.jp
Source
FEMS Microbiol Lett, 177(2):231-5 1999 Aug 15
Abstract
The nucleotide sequence analysis of the dihydropteroate synthase (DHPS)
gene of six diaminodiphenylsulfone-resistant Mycobacterium leprae strains
revealed that the mutation was limited at highly conserved amino acid
residues 53 or 55. Though the mutation at amino acid residue 55 or its
homologous site has been reported in other bacteria, the mutation at
residue 53 is the first case in bacteria. This is the first paper which
links the mutations in DHPS and sulfonamide resistance in M. leprae. This
finding is medically and socially relevant, since leprosy is still a big
problem in certain regions.
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23.) In vitro activity of epiroprim, a dihydrofolate reductase inhibitor,
singly and in combination with brodimoprim and dapsone, against
Mycobacterium leprae.
============================================================
Author
Dhople AM
Address
Department of Biological Sciences, Florida Institute of Technology,
Melbourne 32901, USA. adhople@fit.edu
Source
Int J Antimicrob Agents, 12(4):319-23 1999 Aug
Abstract
The antimicrobial effects of a new dihydrofolate reductase inhibitor,
epiroprim, alone and in combination with dapsone and brodimoprim against
Mycobacterium leprae were evaluated in vitro in cell-free culture system.
Two biochemical parameters were used to measure metabolic activity (and
growth) of the organism. The minimal inhibitory activity of epiroprim
against M. leprae was 10 mg/l and the action was bactericidal. When
combined with dapsone, epiroprim exhibited a strong synergism; on the
other hand, combination of epiroprim and brodimoprim provided only
additive effects. The results suggest that epiroprim can be a component in
multidrug therapy regimen in leprosy.
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24.) Lymphoproliferative responses of leprosy patients and healthy
controls to nitrocellulose-bound M. leprae antigens.
============================================================
Author
Sachdeva G; Kaur G; Bhutani LK; Bamezai RN
Address
Human Genetics Laboratory, School of Life Sciences, Jawaharlal Nehru
University, New Delhi, India.
Source
Int J Lepr Other Mycobact Dis, 67(2):133-42 1999 Jun
Abstract
The lymphoproliferative responses of 51 leprosy patients and 11 healthy
contacts were analyzed using the nitrocellulose-bound specific antigen
fractions from the cell-free extract of Mycobacterium leprae. The main
proliferation-inducing fraction for peripheral blood mononuclear cells of
the healthy contacts was found to be the Fraction II, bearing antigens in
the range of 66-45 kDa. However, this fraction failed to induce
lymphoproliferation in the leprosy patients, unlike healthy contacts (p
< 0.032). The number of responders as well as the strength of the
responses to 66-45 kDa proteins were found to be low in the leprosy
patients compared to the healthy contacts. Further, preliminary analysis
with the subfractions of Fraction II produced a similar pattern,
suggesting that the immune response to the antigens in the range of 66-45
kDa M. leprae proteins remains suppressed in subjects with clinical signs
and symptoms of the disease.
============================================================
25.) Dominant recognition of a cross-reactive B-cell epitope in
Mycobacterium leprae 10 K antigen by immunoglobulin G1 antibodies across
the disease spectrum in leprosy.
============================================================
Author
Hussain R; Dockrell HM; Chiang TJ
Address
Department of Microbiology, The Aga Khan University. PO Box 3500, Karachi,
Pakistan.
Source
Immunology, 96(4):620-7 1999 Apr
Abstract
Mycobacterium leprae-specific immunoglobulin G1 (IgG1) antibodies in
patients with leprosy show a direct correlation with bacterial load
(rho=0.748; P<0002) suggesting that IgG1 B-cell responses may be
surrogate markers of disease progression. To investigate if this
upregulation was a general feature of IgG1 responses to all M. leprae (ML)
antigens, we analysed responses to several recombinant purified ML
heat-shock proteins (HSP). Three recombinant HSPs (ML10 K, ML 18 K and ML
65 K) were tested for their ability to induce various IgG subclasses in
patients with either the lepromatous (LL/BL, n=26) or tuberculoid form
(BT/TT, n=39) of the disease as well as in healthy households (HC, n=14)
and endemic controls (EC=19). Our major findings were: (1) selective
augmentation of IgG1 antibody responses to ML10 K; (2) recognition of a
restricted number of epitopes across the disease spectrum and healthy
controls by IgG1 antibodies; (3) dominant recognition of cross-reactive
epitopes which were common to both ML and MT 10 K. This response was not
related to contamination with endotoxin. Epitope mapping using 15-mer
overlapping peptides spanning the ML 10 000 MW revealed an immunodominant
IgG1 binding peptide (aa41-55) in patients as well as healthy controls.
This peptide is a shared epitope with M. tuberculosis 10 K suggesting that
postswitched IgG1 B cells recognizing this epitope rather than naive B
cells are being expanded.
============================================================
26.) Immune responses to recombinant proteins of Mycobacterium leprae.
============================================================
Author
Wilkinson KA; Katoch K; Sengupta U; Singh M; Sarin KK; Ivanyi J; Wilkinson
RJ
Address
Medical Research Council Clinical Sciences Center, Imperial College of
Science, Technology, and Medicine, Hammersmith Hospital, London, W12 ONN,
United Kingdom. kaw10@po.cwru.edu
Source
J Infect Dis, 179(4):1034-7 1999 Apr
Abstract
Identification of antigenic determinants of the polar immune response in
leprosy may illuminate both protection and pathogenesis. Thirty subjects
were studied (22 with polar disease and 8 healthy controls who were
heavily exposed but disease-free) by assaying the proliferative,
interferon (IFN)-gamma, and antibody responses to recombinant antigens of
Mycobacterium leprae (10, 28, 36, and 65 kDa). The 10-kDa antigen elicited
IFN-gamma production from all tuberculoid (TT) and borderline tuberculoid
(BT) patients but little from controls, lepromatous (LL), or borderline
lepromatous (BL) patients (P<.05). Production of 65-kDa-specific
IFN-gamma was higher in TT/BT than in controls or LL/BL patients
(P<.006). All subjects produced 65-kDa-specific antibody, but it was
higher in LL/BL patients than in healthy controls, whose responses were
higher than in TT/BT subjects (P=.035). The 36-kDa antibody responses were
selectively increased in LL/BL subjects (P<.02). The intermediate
phenotype of the controls suggests that M. leprae-specific production of
IFN-gamma may contribute to pathology and to protection in leprosy.
============================================================
27.) Causative organism and host response. International Leprosy Congress,
============================================================
Beijing, 7-12 September 1998. Workshop report.
Author
Krahenbuhl JL
Source
Lepr Rev, 70(1):95-102 1999 Mar
Abstract
Whether or not the leprosy elimination target is met in all endemic
countries by the year 2000, the MDT programme will have greatly reduced
worldwide prevalence. However, our workshop chairmen were asked to ignore
the prevalence-based leprosy 'elimination' programme and focus on
recommendations for a long term, incidence-based eradication target where
transmission is blocked. They were asked to be concerned with basic
leprosy research goals in the post 2000 era. The members of our workshops
are actively productive workers, committed to their special interests.
They are fully cognizant of the obstacles faced daily in working with
leprosy and M. leprae, the requirement for clever experimental design even
with the availability of the powerful tools of molecular biology which can
now be brought to bear on some of the research obstacles. They are also
aware of our lack of understanding about leprosy and M. leprae. How do you
block transmission if you don't know how infection is transmitted? Can
infection be detected, diagnosis made earlier? Is there a non-human
reservoir host, a carrier state, an environmental source? What is the
basis of M. leprae's predilection for nerves, the mechanisms underlying
reactions? What needs to be targeted to treat reactions? Can a vaccine
play a role? There is nothing startling in the workshops' recommendations.
Other individuals and groups of experts have made the same suggestions,
with slightly varying priorities. What one can read between the lines of
these reports, is a sense of urgency to get as much done as soon as
possible. Worldwide interest in leprosy will soon be diminished, not by
design but as a consequence of the laudable success of the MDT programme.
The experiment is still underway, but chemotherapy alone, killing bacilli
in the detectable human host, does not appear to be the answer to blocking
transmission. A number of goals must be addressed while there are still
intact national and international leprosy programmes, while there are
still leprosy treatment and research centres that can co-ordinate and
facilitate the necessary trials for early diagnosis, early detection of
reactions, evaluation of immunosuppressive regimens for reactions. A key
recommendation is concerned with the means of measuring progress. A clear
and explicit means of reporting incidence, prevalence and 'case detection'
should be implemented to avoid a distorted picture of worldwide leprosy.
These recommendations are non-controversial. What should be done is clear.
The uncertainty is in determining who will do the work. Who will fund the
laboratories engaged in this work? Look around you. There are fewer
scientists attending this Congress but browsing the abstracts and
attending our sessions and posters clearly revealed to me that fewer of us
are doing far better work than in the past. Alternative sources of funding
will help. Tuberculosis research is enticing researchers away from leprosy
in the developed countries but is visibly sustaining leprosy research in
many centres in developing countries. Formation of alliances was a key
goal of this Congress. I asked my colleagues from Carville to identify in
their own discipline, dedicated people, committed laboratories that will
sustain their leprosy research efforts over the next 5, 10 or more years.
These are the people with whom we wish to collaborate, form alliances,
share resources and expertise, address the future of worldwide leprosy.
============================================================
28.) Immunohistological analysis of in situ expression of mycobacterial
antigensin skin lesions of leprosy patients across the histopathological
spectrum. Association of Mycobacterial lipoarabinomannan (LAM) and
Mycobacterium leprae phenolic glycolipid-I (PGL-I) with leprosy reactions.
============================================================
Author
Verhagen C; Faber W; Klatser P; Buffing A; Naafs B; Das P
Address
Departments of Dermatology, Academic Medical Center, University of
Amsterdam, The Netherlands.
Source
Am J Pathol, 154(6):1793-804 1999 Jun
Abstract
The presence of mycobacterial antigens in leprosy skin lesions was studied
by immunohistological methods using monoclonal antibodies (MAbs) to
Mycobacterium leprae-specific phenolic glycolipid I (PGL-I) and to
cross-reactive mycobacterial antigens of 36 kd, 65 kd, and
lipoarabinomannan (LAM). The staining patterns with MAb to 36 kd and 65 kd
were heterogeneous and were also seen in the lesions of other skin
diseases. The in situ staining of PGL-I and LAM was seen only in leprosy.
Both antigens were abundantly present in infiltrating macrophages in the
lesions of untreated multibacillary (MB) patients, whereas only PGL-I was
occasionally seen in scattered macrophages in untreated paucibacillary
lesions. During treatment, clearance of PGL-I from granulomas in MB
lesions occurred before that of LAM, although the former persisted in
scattered macrophages in some treated patients. This persistence of PGL-I
in the lesions paralleled high serum anti-PGL-I antibody titers but was
not indicative for the presence of viable bacilli in the lesions.
Interestingly, we also observed a differential expression pattern of PGL-I
and LAM in the lesions of MB patients with reactions during the course of
the disease as compared with those without reactions. In conclusion, the
in situ expression pattern of PGL-I and LAM in MB patients may assist in
early diagnosis of reactions versus relapse.
============================================================
29.) IL-18 promotes type 1 cytokine production from NK cells and T cells
in human intracellular infection.
============================================================
Author
Garc´ia VE; Uyemura K; Sieling PA; Ochoa MT; Morita CT; Okamura H;
Kurimoto
M; Rea TH; Modlin RL
Address
Division of Dermatology and Department of Microbiology and Immunology,
University of California, Los Angeles, CA 90095, USA.
Source
J Immunol, 162(10):6114-21 1999 May 15
Abstract
We investigated the role of IL-18 in leprosy, a disease characterized by
polar cytokine responses that correlate with clinical disease. In vivo,
IL-18 mRNA expression was higher in lesions from resistant tuberculoid as
compared with susceptible lepromatous patients, and, in vitro, monocytes
produced IL-18 in response to Mycobacterium leprae. rIL-18 augmented M.
leprae-induced IFN-gamma in tuberculoid patients, but not lepromatous
patients, while IL-4 production was not induced by IL-18. Anti-IL-12
partially inhibited M. leprae-induced release of IFN-gamma in the presence
of IL-18, suggesting a combined effect of IL-12 and IL-18 in promoting M.
leprae-specific type 1 responses. IL-18 enhanced M. leprae-induced
IFN-gamma production rapidly (24 h) by NK cells and in a more sustained
manner (5 days) by T cells. Finally, IL-18 directly induced IFN-gamma
production from mycobacteria-reactive T cell clones. These results suggest
that IL-18 induces type 1 cytokine responses in the host defense against
intracellular infection.
============================================================
30.) Identification of M.leprae in conjunctiva of leprosy patients using
the superior tarsal conjunctiva scrape technique.
============================================================
Author
Campos WR; Rodrigues CA; Or´efice F; Monteiro LG
Address
S~ao Geraldo Hospital, Medical School, Federal University of Minas Gerais,
Belo Horizonte, Brazil.
Source
Indian J Lepr, 70(4):397-403 1998 Oct-Dec
Abstract
The technique of superior tarsal conjunctiva scrape was used for
identifying M.leprae in the conjunctiva in 56 leprosy patients (all of
them multibacillary, some untreated and others treated with multidrug
therapy). The technique of tarsal conjunctiva scrape was shown to be more
suitable than conjunctival biopsy for identifying lepra bacilli. This
technique is also easier to perform and has shown a statistical relation
between bacilloscopical index of skin (BIsk) and bacilloscopical index of
tarsal conjunctiva (BIconj) values. Thus, if the bacilli can be identified
at tarsal conjunctiva we can assume greater systemic bacillary load in the
patients.
============================================================
31.) [Present situation of leprosy in highly endemic area of tropical
Asia--a seroepidemiological study of Mycobacterium leprae infection in
general inhabitants]
============================================================
Author
Izumi S; Budiawan T; Matsuoka M; Saeki K; Kawatsu K
Address
National Leprosarium Oshima Seisho-En, Kagawa, Japan.
Source
Nihon Hansenbyo Gakkai Zasshi, 67(3):401-8 1998 Nov
Abstract
One of the most important unsolved problems in epidemiology of leprosy is
the heterogeneous geographic distribution of the disease. There are highly
endemic area called "Pocket" in the endemic countries. Little is known why
leprosy is so endemic in the area. We conducted, therefore, an
epidemiological study on M. leprae infection and distribution of leprosy
bacilli in the environment by using serological and molecular biological
techniques. It was found that considerable number of general inhabitants
in the pocket are infected with leprosy bacilli and more than 20% of the
villagers are carrying M. leprae on the surface of the nasal cavity;
suggesting that leprosy bacilli in the residential environment play an
important role in high prevalence of leprosy in the endemic area. New
preventive measures such as chemoprophylaxis, in addition to MDT, will be
needed for global elimination of the disease.
============================================================
32.) Anti M. leprae IgM antibody determination by
ultramicroimmunoenzymatic (UMELISA HANSEN) for the diagnosis and
monitoring leprosy.
============================================================
Author
Torrella A; Solis RL; Perez E; Medina Y; Kerguelen C; Olaya P
Address
Immunoassay Center, C. Habana, Cuba.
Source
Rev Inst Med Trop Sao Paulo, 40(3):177-81 1998 May-Jun
Abstract
The relationship between the IgM antibody response, antigenic load as well
as the clinical improvement after chemotherapy was studied in order to
obtain useful data for the early diagnosis and monitoring leprosy. A level
of 82% (94/115) agreement was obtained between IgM UMELISA HANSEN and
slit-skin smear examination. Discrepant results were observed in 16
patients who showed positive IgM response despite negative by the skin
smear examination. In these patients, the IgM response was seen to be
associated to the early signal for bacilli recurrence in the skin. In one
of these patients the presence of bacilli was demonstrated in the skin,
two months after IgM antibodies being detected by UMELISA HANSEN. Also in
one of the treated patients positive by both diagnostic techniques, a
remarkable decrease in the IgM antibody levels was seen, correlating with
a significant clinical improvement. Moreover it was found a direct
relationship between the IgM antibody response and bacterial antigenic
load, regardless the time elapsed in the disease's evolution.
============================================================
33.) Opposite cellular accumulation and nitric oxide production in vivo
after pleural immunization with M. leprae or M. bovis BCG.
============================================================
Author
Moura AC; Werneck-Barroso E; Rosas EC; Henriques MG; Cordeiro RS
Address
Department of Cell Biology and Genetics, Universidade do Rio de Janeiro
(UERJ), Rio de Janeiro, Brazil.
Source
Int J Mol Med, 3(1):69-74 1999 Jan
Abstract
Mycobacteria as intracellular pathogens have evolved mechanisms to survive
within macrophages. Our previous data showed that M. leprae (ML), unlike
M. bovis BCG, did not induce an inflammatory response in the mice
subcutaneous tissue. Further, ML inhibited BCG-induced foot pad oedema and
seemed to transform macrophages in epithelioid cells. Since these
mycobacteria share common antigens, here we seeked to compare the acute
and chronic cellular response evoked by ML and BCG in pleurisy of a
mycobacteria-susceptible mice (BALB/c). The total leukocytes, the cell
type that migrated to the pleural cavity and macrophage activation assayed
by nitric oxide release were determined. Live or dead BCG Moreau recruited
the same extent of cells, essentially monocytes and neutrophils,
dose-dependently, in both acute and chronic pleurisy. BCG-induced
eosinophilia was observed only in the acute response (after 24 h of
injection). A significant nitric oxide release by pleural macrophages was
triggered by BCG Moreau without previous activation. Nevertheless, ML
failed to recruit leukocytes to the pleural space or to lead to nitric
oxide production despite the number of bacilli used and the time studied
(1, 7 or 14 days after injection). Although these mycobacteria have common
antigens that cross-react, these data show a distinct ability of ML or BCG
to recruit cells to the pleural space and to activate pleural macrophage
for nitric oxide production in vivo.
============================================================
34.) Use of a whole blood assay to monitor the immune response to
mycobacterial antigens in leprosy patients: a predictor for type 1
reaction onset?
============================================================
Author
Weir RE; Butlin CR; Neupane KD; Failbus SS; Dockrell HM
Address
Department of Infectious and Tropical Diseases, London School of Hygiene
&
Tropical Medicine, UK.
Source
Lepr Rev, 69(3):279-93 1998 Sep
Abstract
Longitudinal studies are more appropriate than cross-sectional studies for
investigating changes in the immune response to Mycobacterium leprae
during leprosy, such as occur in type 1 (reversal) reactions. A test for
predicting the onset of reactions in leprosy would greatly reduce
disability associated with leprosy. Whole blood assays are appropriate for
longitudinal studies of the in vitro T-cell response, as they are robust
and reproducible, and require only a small volume of blood. Whole blood
assays were used to assess the natural variation in the 'normal' T-cell
response to mycobacterial antigens in healthy UK donors, and healthy
Nepali donors, tested over 6 months. This was compared with variation in
T-cell responses measured over 6 months in 22 leprosy patients in Nepal,
including eight who developed type 1 reactions during this time. The in
vitro T-cell response to M. leprae sonicate, M. tuberculosis PPD, the
mitogen PHA, and (in the UK study) recombinant mycobacterial antigens (70
kD and 30/31 kD proteins) was measured by lymphoproliferation and
interferon-gamma (IFN gamma) responses, and variation in responses over
time in each subject calculated as a coefficient of variation (CV). The
baseline high, low or non-responder status of the healthy UK donors
remained stable. The magnitude of IFN gamma responses varied by mean CV
ranging from 26% (to PPD) to 63% (to Mtb 70 kD); proliferation responses
showed less variation, ranging from mean CV of 18% (to PHA) to 47% (to Mtb
70 kD). Response variation was independent of lymphocyte number in
culture. Similar variation in lymphoproliferation responses to MLS, PPD
and PHA was observed in the group of healthy Nepali subjects, and in
Nepali leprosy patients who did not experience reactions during the study.
Of the eight leprosy patients who developed type 1 reactions, four (two
BT, one BB, one BL) showed significantly increased proliferation to MLS at
the time of reaction (74-300% above baseline); four (one BB, two BL, one
LL) remained low or non-responders to MLS throughout. An alternative
marker of immune response--anti-phenolic glycolipid-1 (PGL-1) antibody
titre--was not predictive of reaction onset in these patients. This study
demonstrated that whole blood assays provide reproducible in vitro
measurements that can be used to monitor changes in T-cell responses to M.
leprae antigens; their practical use as a diagnostic marker of type 1
reaction onset is discussed.
============================================================
35.) A clinical and bacteriological examination of Mycobacterium leprae in
the epidermis and cutaneous appendages of patients with multibacillary
leprosy.
============================================================
Author
Hosokawa A
Address
Department of Dermatology, Ryukyu University School of Medicine, Okinawa,
Japan.
Source
J Dermatol, 26(8):479-88 1999 Aug
Abstract
In the specimens examined at Ryukyu University Hospital, acid-fast bacilli
(AFB) were observed in the epidermis, cutaneous appendages and endothelial
cells of capillaries. These specimens were taken from non-ulcerating skin
lesions of patients with multibacillary leprosies such as LL and
borderline lepromatous leprosy (BL). Of the 211 specimens examined, 23
(10.9%) were AFB-positive [AFB (+)] in the above mentioned skin regions.
These AFB (+) samples were taken from nine leprosy patients; six cases (17
samples) of LL, two cases (5 samples) of BL, and one case (one sample) of
BB. The AFB positive rate [AFB (+)-rate] in the above mentioned skin
regions was high in the unmedicated LL sample (50.0%, 7/14) and low in the
medicated mid-borderline leprosy (BB) samples (0.0%, 0/10). Particularly
in the intraepidermal eccrine sweat duct (acrosyringium), a relatively
high number of AFB were observed. The AFB (+)-rate appears likely to be
higher in non-ulcering skin lesions with minor inflammation or in lesions
with leprosy reaction than typical skin lesions such as papules, nodules,
and infiltrated punched out skin lesions. Although the possibility that
viable bacilli could be excreted from non-ulcerating skin lesions appeared
to be small, these lesions were suspected of being a possible source of
infection.
============================================================
36.) Quality control tests for vaccines in leprosy vaccine trial, Avadi.
============================================================
Author
Sreevatsa; Hari M; Gupte MD
Address
BCG Vaccine Laboratory, Guindy, Chennai.
Source
Indian J Lepr, 70(4):389-95 1998 Oct-Dec
Abstract
All the vaccines supplied for the large scale comparative leprosy vaccine
trial of ICRC bacilli, M.w, BCG plus killed M. leprae (candidate
vaccines), BCG and normal saline (control arms) at CJIL Field Unit,
Chennai were tested for quality control by the suppliers following the
procedures laid down in the WHO protocol for killed M. leprae. Quality
control for BCG was carried out at BCG vaccine laboratory as per protocol.
Toxicity and sterility tests were done on all the vaccine batches/lots
received. As part of the quality control, bacterial count, and protein
estimation were also done. Studies showed that the bacterial content and
protein concentration were comparable with the original preparations.
Vaccines were free from micro-organisms, toxic materials and safe for
human use. Thus the quality of all vaccine preparations was satisfactory.
============================================================
37.) Comparative leprosy vaccine trial in south India.
============================================================
Author
Gupte MD; Vallishayee RS; Anantharaman DS; Nagaraju B; Sreevatsa;
Balasubramanyam S; de Britto RL; Elango N; Uthayakumaran N; Mahalingam VN;
Lourdusamy G; Ramalingam A; Kannan S; Arokiasamy J
Source
Indian J Lepr, 70(4):369-88 1998 Oct-Dec
Abstract
This report provides results from a controlled, double blind, randomized,
prophylactic leprosy vaccine trial conducted in South India. Four
vaccines, viz BCG, BCG+ killed M. leprae, M.w and ICRC were studied in
this trial in comparison with normal saline placebo. From about 3,00,000
people, 2,16,000 were found eligible for vaccination and among them,
1,71,400 volunteered to participate in the study. Intake for the study was
completed in two and a half years from January 1991. There was no instance
of serious toxicity or side effects subsequent to vaccination for which
premature decoding was required. All the vaccine candidates were safe for
human use. Decoding was done after the completion of the second resurvey
in December 1998. Results for vaccine efficacy are based on examination of
more than 70% of the original "vaccinated" cohort population, in both the
first and the second resurveys. It was possible to assess the overall
protective efficacy of the candidate vaccines against leprosy as such.
Observed incidence rates were not sufficiently high to ascertain the
protective efficacy of the candidate vaccines against progressive and
serious forms of leprosy. BCG+ killed M. leprae provided 64% protection
(CI 50.4-73.9), ICRC provided 65.5% protection (CI 48.0-77.0), M.w gave
25.7% protection (CI 1.9-43.8) and BCG gave 34.1% protection (CI
13.5-49.8). Protection observed with the ICRC vaccine and the combination
vaccine (BCG+ killed M. leprae) meets the requirement of public health
utility and these vaccines deserve further consideration for their
ultimate applicability in leprosy prevention.
============================================================
38.) Evolutionary bottlenecks in the agents of tuberculosis, leprosy, and
paratuberculosis.
============================================================
Author
Frothingham R
Address
Infectious Disease Section, Durham Veterans Affairs Medical Center,
Durham,
North Carolina 27705, USA. rfr@galactose.mc.duke.edu
Source
Med Hypotheses, 52(2):95-9 1999 Feb
Abstract
Parasitic mycobacteria cause important human and animal diseases including
tuberculosis, leprosy, and paratuberculosis. Several methods demonstrate a
high degree of sequence conservation in three parasitic mycobacterial
species (Mycobacterium tuberculosis, M. leprae, and M. avium subspecies
paratuberculosis). Each of these species has completely conserved
deoxyribonucleic acid (DNA) sequence in an internal transcribed spacer. In
contrast, several species of environmental mycobacteria (M.
intracellulare, M. kansasii, M. gordonae, and M. scrofulaceum) have
substantial strain-to-strain variation in this region. These data suggest
that each of the parasitic species has gone through a recent evolutionary
bottleneck. Comparisons of tandem-repeat DNA from ancient and modern
mycobacterial strains may allow this hypothesis to be tested directly.
============================================================
39.) Role of S-100 staining in differentiating leprosy from other
granulomatous diseases of the skin.
============================================================
Author
Thomas MM; Jacob M; Chandi SM; George S; Pulimood S; Jeyaseelan L; Job CK
Address
Department of Dermatology, Christian Medical College and Hospital,
Vellore,
Tamil Nadu, India.
Source
Int J Lepr Other Mycobact Dis, 67(1):1-5 1999 Mar
Abstract
Since Mycobacterium leprae are rarely demonstrable in the tuberculoid
spectrum of leprosy, a confirmatory diagnosis of leprosy can be made on
the basis of finding active destruction of cutaneous nerves by
granulomatous inflammation in a skin biopsy. Immunoperoxidase staining for
S-100 protein, which is a marker for Schwann cells, was used to delineate
nerves in lesional skin biopsies of 25 patients with tuberculoid and
borderline tuberculoid leprosy as well as 15 controls with nonleprous
granulomatous inflammation. Four different patterns of nerve damage were
observed: infiltrated, fragmented, absent, and intact. All of the
nonleprous granulomatous dermatoses showed only intact nerves, either
inside or outside the granuloma, and so S-100 staining can be used to rule
out leprosy.
============================================================
40.) Assessment of anti-PGL-I as a prognostic marker of leprosy reaction.
============================================================
Author
Stefani MM; Martelli CM; Morais-Neto OL; Martelli P; Costa MB; de Andrade
AL
Address
Department of Immunology, University Hospital, Federal University of
Goias,
Goiania, Brazil. stefani@internetional.com.br
Source
Int J Lepr Other Mycobact Dis, 66(3):356-64 1998 Sep
Abstract
The anti-phenolic glycolipid-I (PGL-I) assay as currently applied for
leprosy is conceived as an early marker of asymptomatic infection, early
disease diagnosis and cure monitoring. Its use as a prognostic marker of
reaction is still a matter of controversy. We conducted a case-control
study to investigate whether IgM and IgG anti-PGL-I antibodies could
discriminate patients at increased risk of developing reactions. Eligible
cases were untreated leprosy patients at the onset of type 1 and type 2
reactions recruited from among 600 concurrent, newly detected, untreated
leprosy patients attending an outpatient clinic in central Brazil. For the
patients with reaction, approximately the same number of leprosy cases
without reaction matched as to bacterial index (BI), age and gender were
randomly selected. Individuals without clinical leprosy were evaluated as
healthy controls. Sera from type 1 reaction (N = 43) and type 2 reaction
(N = 26) patients were tested by an ELISA using PGL-I synthetic
disaccharide-BSA antigen and 1:300 sera dilution (cut-off point > or =
0.2 OD). Antibody profiles were evaluated by exploratory data analysis and
reverse cumulative distribution curves. The IgG anti-PGL-I response did
not have a defined pattern, being detected only at low levels. Our results
indicate that leprosy patients, independently of their reactional status,
produce high levels of IgM anti-PGL-I, demonstrating a strong correlation
between the magnitude of antibody response and the BI. Patients with a
higher BI were at least 3.4 times more prone to produce an antibody
response compared to healthy controls.
============================================================
41.) Conjunctival biopsy in patients with leprosy.
============================================================
Author
Campos WB; Or´efice F; Sucena MA; Rodrigues CA
Address
S~ao Geraldo Hospital, Medical School of the Federal University of Minas
Gerais, Brazil.
Source
Indian J Lepr, 70(3):291-4 1998 Jul-Sep
Abstract
The authors examined the eyes of 120 leprosy patients comprising of 30
cases each of tuberculoid, indeterminate, borderline and lepromatous
leprosy. The investigation included biopsy of the bulbar conjunctiva on
the upper temporal quadrant of the right eye. The study patients included
both who were untreated, those that were being treated and those who were
in observation after the end of treatment. The aim of the study was to
identify the presence of M. leprae in the conjunctiva. Four such cases
were found: one borderline patient with no treatment and three lepromatous
patients who were being treated with MDT.
============================================================
42.) Experimental leprosy in rhesus monkeys: transmission, susceptibility,
clinical and immunological findings.
============================================================
Author
Gormus BJ; Xu K; Baskin GB; Martin LN; Bohm RP Jr; Blanchard JL; Mack PA;
Ratterree MS; Meyers WM; Walsh GP
Address
Department of Microbiology, Pathology, Tulane Regional Primate Research
Center, Covington, LA 70433, USA.
Source
Lepr Rev, 69(3):235-45 1998 Sep
Abstract
A total of 46 Rhesus monkeys (RM) was inoculated with Mycobacterium leprae
(ML) and followed clinically and immunologically for extended periods.
Twenty-one (45.7%) of the RM developed leprosy spanning the known leprosy
spectrum, with six of 21 (28.6%) having disease in the borderline
lepromatous to lepromatous area of the spectrum. RM with paucibacillary
forms of leprosy produced predominantly IgG anti-phenolic glycolipid
(PGL-I) antibodies and positive lepromin skin test and/or in vitro
blastogenesis responses; IgM anti-PGL-I predominated in animals with BB-LL
leprosy and correlated with negative immune responses to lepromin. IgG
anti-PGL-I antibodies persisted in a number of RM for several years
without histopathological evidence of leprosy, suggesting possible
persisting subclinical infection. The data show that RM are a valuable
model for the study of leprosy. Eleven of the 46 RM were inoculated with
ML from sources infected with simian immunodeficiency virus (SIV), the
monkey counterpart to the human immunodeficiency virus (HIV). The possible
effect of SIV on the clinical outcome of ML infection could not be
determined due to insufficient numbers of animals to yield statistically
significant results.
============================================================
43.) Lepromatous uveitis diagnosed by iris biopsy.
============================================================
Author
Messmer EM; Raizman MB; Foster CS
Address
University Eye Hospital, Munich, Germany.
Source
Graefes Arch Clin Exp Ophthalmol, 236(9):717-9 1998 Sep
Abstract
Ocular leprosy is rarely seen in developed countries. We report the
long-term follow-up of a patient with bilateral uveitis, glaucoma, and
keratitis. Skin, iris and aqueous humor biopsies disclosed abundant
Wade-Fite-positive organisms consistent with Mycobacterium leprae. Leprosy
must be considered in the differential diagnosis of keratitis and uveitis.
============================================================
44.) Preservation of Mycobacterium leprae in vitro for four years by
lyophilization.
============================================================
ARTICLE SOURCE: Int J Lepr Other Mycobact Dis (United States), Sep 1993,
61(3) p415-20
AUTHOR(S): Kohsaka K; Matsuoka M; Hirata T; Nakamura M
PUBLICATION TYPE: JOURNAL ARTICLE
ABSTRACT: Although the viability of Mycobacterium leprae suspended in
distilled water with or without 10% fetal calf serum was reduced
approximately 10(-2) to 10(-4) from that of the starting material during
the process of lyophilization, bacilli capable of multiplication in nude
mouse foot pads were found in the lyophilized samples stored for 4 years
at 4 degrees C. The multiplication rate of the lyophilized bacilli which
were suspended in 10% serum-water was much higher than that of the bacilli
suspended in water only. On the other hand, no reduction of the viability
of M. leprae suspended in 10% skim milk-water was demonstrated during the
process of lyophilization as well as storage for 2 years at 4 degrees C.
From the results obtained here, it could be suggested that M. leprae might
be preserved in vitro by means of lyophilized M. leprae was extremely
stable during cryopreservation when the bacilli were suspended in 10% skim
milk-water. Therefore, the composition of the solution for suspending the
bacilli is definitely critical for the maintenance of M. leprae viability
by means of lyophilization.
=========================================================================
45.) Minocycline in lepromatous leprosy.
=========================================================================
Author
Fajardo TT Jr; Villahermosa LG; dela Cruz EC; Abalos RM; Franzblau SG;
Walsh GP
Address
Clinical Research Branch, Leonard Wood Memorial Center, Cebu City, The
Philippines.
Source
Int J Lepr Other Mycobact Dis, 63(1):8-17 1995 Mar
Abstract
Twelve patients were treated with three dose levels of minocycline for 30
days, primarily to detect the dose-related effects on Mycobacterium leprae
viability, followed by another 5 months of daily minocycline for overall
efficacy and persistence of clinical and antibacterial effects.
Subsequently, the patients were given standard WHO/MDT chemotherapy for
multibacillary leprosy. Clinical improvement was recognizable during the
first month, occurring much earlier among those on minocycline 200 mg
daily than those who received minocycline 100 mg daily. A similar change
also was observed in one patient 11 days after three daily doses of 100 mg
of minocycline. At the end of 6 months, all patients were clinically
improved with a slight reduction in the average bacterial index (BI) and
logarithmic index of bacilli in biopsy (LIB). The effects of minocycline
on viability by mouse foot pad inoculation and palmitic acid oxidation
assays were noted beginning at 10 to 14 days of daily dosing and becoming
more definite after 30 days of treatment. Both tests correlated fairly
well. Doses of 200 mg daily did not appear to be more efficient than
minocycline 100 daily. Phenolic glycolipid-I (PGL-I) antigen
determinations done on some patients during the first month remained
positive and did not correlate with changes in viability results. At the
end of 6 months, after 5 months of 100 mg of minocycline monotherapy, no
viable organisms could be demonstrated by mouse foot pad inoculation and
palmitic acid oxidation assays; assays for PGL-I antigen were all
negative.(ABSTRACT TRUNCATED AT 250 WORDS)
=========================================================================
46.) Efficacy of minocycline in single dose and at 100 mg twice daily for
lepromatous leprosy.
=========================================================================
Int J Lepr Other Mycobact Dis (United States), Dec 1994, 62(4) p568-73
AUTHOR(S): Gelber RH; Murray LP; Siu P; Tsang M; Rea TH
AUTHOR'S ADDRESS: San Francisco Regional Hansen's Disease Program, CA
94115.
PUBLICATION TYPE: CLINICAL TRIAL; JOURNAL ARTICLE
ABSTRACT: A clinical trial of minocycline in a total of 10 patients with
previously untreated lepromatous leprosy was conducted in order to
evaluate the efficacy of a single, initial, 200-mg dose and 100 mg twice
daily of minocycline for a total duration of up to 3 months. Patients
improved remarkably quickly. Although single-dose therapy did not result
in a significant killing of Mycobacterium leprae, viable M. leprae were
cleared from the dermis regularly by 3 months of twice-daily therapy, a
rate similar to that achieved by minocycline 100 mg once daily. Because
more side effects were noted herein than previously with 100 mg daily, we
recommend that minocycline, when applied, be administered at 100 mg daily
to leprosy patients.
=========================================================================
47.) Field trial on efficacy of supervised monthly dose of 600 mg
rifampin,
400 mg ofloxacin and 100 mg minocycline for the treatment of leprosy;
first results.
=========================================================================
Author
Mane I; Cartel JL; Grosset JH
Address
Institut de Leprologie Appliquee, Dakar CD Annexe, Senegal.
Source
Int J Lepr Other Mycobact Dis, 65(2):224-9 1997 Jun
Abstract
In 1995, a field trial was implemented in Senegal in order to evaluate the
efficacy of a regimen based on the monthly supervised intake of rifampin
600 mg, ofloxacin 400 mg and minocycline 100 mg to treat leprosy. During
the first year of the trial, 220 patients with active leprosy (newly
detected or relapsing after dapsone monotherapy) were recruited: 102
paucibacillary (PB) (60 males and 42 females) and 118 multibacillary (MB)
(71 males and 47 females). All of them accepted the new treatment (none
requested to be preferably put under standard WHO/MDT), no clinical sign
which could be considered as a toxic effect of the drug was noted, and
none of the patients refused to continue treatment because of any clinical
trouble. The compliance was excellent: the 113 patients (PB and MB)
detected during the first 6 months of the trial have taken six monthly
doses in 6 months, as planned. The rate of clearance and the progressive
decrease of cutaneous lesions was satisfactory. Although it is too soon to
give comprehensive results, it should be noted that no treatment failure
was observed in the 56 PB patients who have completed treatment and have
been followed up for 6 months. The long-term efficacy of the new regimen
is to be evaluated on the rate of relapse during the years following the
cessation of treatment. If that relapse rate is acceptable (similar to
that observed in patients after treatment with current standard WHO/ MDT),
the new regimen could be a solution to treat, for instance, patients very
irregular and/or living in remote or inaccessible areas since no selection
of rifampin-resistant Mycobacterium leprae should be possible (a monthly
dose of ofloxacin and minocycline being as effective as a dose of dapsone
and clofazimine taken daily for 1 month). Nevertheless, until longer term
results of this and other trials become available, there is no
justification for any change in the treatment strategy, and all leprosy
patients should be put under standard WHO/MDT.
=========================================================================
48.) Bactericidal activity of a single-dose combination of ofloxacin plus
minocycline, with or without rifampin, against Mycobacterium leprae in
mice and in lepromatous patients.
=========================================================================
Author
Ji B; Sow S; Perani E; Lienhardt C; Diderot V; Grosset J
Address
Facult´e de M´edecine Piti´e-Salp^etri`ere, Paris, France.
bacterio@biomath.jussieu.fr
Source
Antimicrob Agents Chemother, 42(5):1115-20 1998 May
Abstract
To develop a fully supervisable, monthly administered regimen for
treatment of leprosy, the bactericidal effect of a single-dose combination
of ofloxacin (OFLO) and minocycline (MINO), with or without rifampin
(RMP), against Mycobacterium leprae was studied in the mouse footpad
system and in previously untreated lepromatous leprosy patients.
Bactericidal activity was measured by the proportional bactericidal
method. In mouse experiments, the activity of a single dose of the
combination OFLO-MINO was dosage related; the higher dosage of the
combination displayed bactericidal activity which was significantly
inferior to that of a single dose of RMP, whereas the lower dosage did not
exhibit a bactericidal effect. In the clinical trial, 20 patients with
previously untreated lepromatous leprosy were treated with a single dose
consisting of either 600 mg of RMP plus 400 mg of OFLO and 100 mg of MINO
or 400 mg of OFLO plus 100 mg of MINO. The OFLO-MINO combination exhibited
definite bactericidal activity in 7 of 10 patients but was less
bactericidal than the RMP-OFLO-MINO combination. Both combinations were
well tolerated. Because of these promising results, a test of the efficacy
of multiple doses of ROM in a larger clinical trial appears justified.
=========================================================================
49.) Efficacy of single dose multidrug therapy for the treatment of
single-lesion paucibacillary leprosy. Single-lesion Multicentre Trial
Group.
=========================================================================
Source
Indian J Lepr, 69(2):121-9 1997 Apr-Jun
Abstract
A multicentre double-blind controlled clinical trial was carried out to
compare the efficacy of a combination of rifampicin 600 mg plus ofloxacin
400 mg plus minocycline 100 mg (ROM) administered as single dose with that
of the standard six-month WHO/MDT/PB regimen. The subjects included 1483
cases with one skin lesion who were previously untreated, were
smear-negative, and had no evidence of peripheral nerve trunk involvement,
and they were randomly divided into study and control groups. The total
duration of the study from the day of intake was 18 months, and 1381
patients completed study. Only 12 patients were categorized as treatment
failure and no difference was observed between the two regimens.
Occurrence of mild side-effects and leprosy reactions were minimal (less
than 1%) in both groups. This study showed that ROM is almost as effective
as the standard WHO/MDT/PB in the treatment of single lesion PB leprosy.
=========================================================================
50.) Bactericidal activity of single dose of clarithromycin plus
minocycline, with or without ofloxacin, against Mycobacterium leprae in
patients.
=========================================================================
Author
Ji B; Jamet P; Perani EG; Sow S; Lienhardt C; Petinon C; Grosset JH
Address
Facult´e de M´edecine Piti´e-Salp^etri`ere, Paris, France.
Source
Antimicrob Agents Chemother, 40(9):2137-41 1996 Sep
Abstract
Fifty patients with newly diagnosed lepromatous leprosy were allocated
randomly to one of five groups and treated with either a month-long
standard regimen of multidrug therapy (MDT) for multibacillary leprosy, a
single dose of 600 mg of rifampin, a month-long regimen with the dapsone
(DDS) and clofazimine (CLO) components of the standard MDT, or a single
dose of 2,000 mg of clarithromycin (CLARI) plus 200 mg of minocycline
(MINO), with or without the addition of 800 mg of ofloxacin (OFLO). At the
end of 1 month, clinical improvement accompanied by significant decreases
of morphological indexes in skin smears was observed in about half of the
patients of each group. A significant bactericidal effect was demonstrated
in the great majority of patients in all five groups by inoculating the
footpads of mice with organisms recovered from biopsy samples obtained
before and after treatment. Rifampin proved to be a bactericidal drug
against Mycobacterium leprae more potent than any combination of the other
drugs. A single dose of CLARI-MINO, with or without OFLO, displayed a
degree of bactericidal activity similar to that of a regimen daily of
doses of DDS-CLO for 1 month, suggesting that it may be possible to
replace the DDS and CLO components of the MDT with a monthly dose of
CLARI-MINO, with or without OFLO. However, gastrointestinal adverse events
were quite frequent among patients treated with CLARI-MINO, with or
without OFLO, and may be attributed to the higher dosage of CLARI or MINO
or to the combination of CLARI-MINO plus OFLO. In future trials,
therefore, we propose to reduce the dosages of the drugs to 1,000 mg of
CLARI, 100 mg of MINO, and 400 mg of OFLO.
=========================================================================
51.) WHO Expert Committee on Leprosy.
=========================================================================
Source: World Health Organ Tech Rep Ser, 874():1-43 1998
Abstract
Considerable progress has been made in the fight against leprosy during
the past 10-15 years, following the introduction of multidrug therapy
(MDT) regimens and the establishment of the goal of eliminating leprosy as
a public health problem by the year 2000. Current estimates indicate that
there are about 1.15 million cases of leprosy in the world, compared with
10-12 million cases in the mid-1980s. This report presents the conclusions
of a WHO Expert Committee convened to review the global leprosy situation
and the technology available for eliminating the disease, to identify the
remaining obstacles to reaching the goal of eliminating leprosy as a
public health problem, and to make appropriate recommendations for the
future on technical and operational matters. The current status of leprosy
elimination is discussed, and the various antileprosy drugs are reviewed,
including the most recently available drugs. On the basis of field trials
and clinical studies, the Committee concludes that a single dose of a
combination of rifampicin, ofloxacin and minocycline is an acceptable and
cost-effective alternative regimen for the treatment of single-lesion
paucibacillary leprosy, and that the duration of the current MDT regimen
for multibacillary leprosy could possibly be shortened to 12 months. The
Committee points out the need for improved management of reactions and
neuritis and prevention of leprosy-related disabilities and impairments,
and recommends that antileprosy activities should become an integral part
of general health services and should involve communities to the fullest
extent possible.
=========================================================================
52.) Experimental evaluation of possible new short-term drug regimens for
treatment of multibacillary leprosy.
=========================================================================
Author
Banerjee DK; McDermott-Lancaster RD; McKenzie S
Address
Department of Medical Microbiology, St George's Hospital Medical School,
London, United Kingdom. banerjee@sghms.ac.uk.
Source
Antimicrob Agents Chemother, 41(2):326-30 1997 Feb
Abstract
Groups of nude mice, with both hind footpads infected with 10(8)
Mycobacterium leprae organisms, were treated with 4-week courses of
different drug combinations. The effect treatment on each group was
evaluated by subinoculating footpad homogenates from the treated mice into
groups of normal and nude mice for subsequent regrowth, assessed 1 year
later. A combination of rifampin (RMP) with clarithromycin (CLARI),
minocycline (MINO), and ofloxacin (OFLO) resulted in the complete killing
of M. leprae after 3 weeks of treatment. A combination of sparfloxacin
(SPAR) and RMP also resulted in a similar bactericidal effect after 3
weeks of treatment. Other drug combinations showed variable effects. Very
little or no effect was observed with any regimen if the treatment was
given for less than 2 weeks. World Health Organization (WHO) multidrug
therapy (MDT) given for 8 weeks was as effective as the two combinations
described above. The results suggest that multidrug combinations
consisting of RMP-OFLO (or SPAR)-CLARI (and/or MINO) are as effective as
the WHO MDT for the treatment of experimental leprosy. Moreover, they
imply that these combinations, which were found to be active in a 4-week
experimental treatment protocol, could be administered as treatment to
patients for a period of time shorter than the present 2-year regimen
without a loss of effectiveness.
=========================================================================
53.) Powerful bactericidal activities of clarithromycin and minocycline
against Mycobacterium leprae in lepromatous leprosy.
=========================================================================
ARTICLE SOURCE: J Infect Dis (United States), Jul 1993, 168(1) p188-90
AUTHOR(S): Ji B; Jamet P; Perani EG; Bobin P; Grosset JH
AUTHOR'S ADDRESS: Faculte de Medecine Pitie-Salpetriere, Paris, France.
PUBLICATION TYPE: CLINICAL TRIAL; JOURNAL ARTICLE; RANDOMIZED
CONTROLLED
TRIAL
ABSTRACT: Thirty-six patients with newly diagnosed lepromatous leprosy
were allocated randomly to three groups and treated for 56 days with
minocycline (100 mg daily), clarithromycin (500 mg daily), or
clarithromycin (500 mg) plus minocycline (100 mg daily). All groups had
rapid and remarkable clinical improvement and significant decline of the
bacterial and morphologic indices in skin smears during treatment. More
than 99% and 99.9% of the viable Mycobacterium leprae had been killed by
28 and 56 days of treatment, respectively, as measured by inoculation of
organisms recovered from skin samples, taken before and during treatment,
into the footpads of immunocompetent and nude mice. Clinical improvement
and bactericidal activity did not differ significantly among the three
groups. Adverse reactions were rare and mild, and no laboratory
abnormality was detected during the trial. Both clarithromycin and
minocycline displayed powerful bactericidal activities against M. leprae
in leprosy patients and may be considered important components of new
multidrug regimens for the treatment of multibacillary leprosy.
=========================================================================
54.) Differential protective effect of bacillus calmette-guerin vaccine
against multibacillary and paucibacillary leprosy in nagpur, india.
=========================================================================
Public Health 1999 Nov;113(6):311-3
Kulkarni HR, Zodpey SP
Department of Preventive and Social Medicine and Clinical Epidemiology
Unit, Government Medical College, Nagpur, India.
For this paper we conducted a secondary data analysis to test the
hypothesis that a linear trend exists in the protective effect of bacillus
Calmette-Guerin (BCG) vaccine against types of leprosy. We used data from
two previous case-control studies to perform an unmatched test for linear
trend. We observed that both the studies revealed a significant linear
trend (P<0.00001). One study that estimated an insignificant protective
effect of BCG against paucibacillary leprosy showed a significant
departure from linearity. We conclude that, the protective effect of BCG
vaccination is differential across severity of leprosy as it brings about
a shift in the immune response to a higher level of cell mediated
immunity. We recommend that future studies dealing with the protective
effect of BCG against leprosy should also conduct an analysis for trend.
=========================================================================
55.) An immunotherapeutic vaccine for multibacillary leprosy.
=========================================================================
Int Rev Immunol 1999;18(3):229-49
Talwar GP
International Centre for Genetic Engineering & Biotechnology, New
Delhi,
India.
On January 30, 1998, a vaccine for leprosy based on Mycobacterium w (the
code word under which this species hitherto unspecified was investigated)
was launched for public use for therapeutic purposes. The vaccine has
completed phase III immunotherapeutic trials as an adjunct to chemotherapy
in urban and rural leprosy control centres and has received the
authorization from the Drugs Controller of India for industrial
manufacture. It will be made available by M/s Cadila Pharmaceuticals,
Ahmedabad. As an adjunct to chemotherapy, the vaccine expediates bacterial
clearance and accelerates clinical regression of lesions. It shortens
significantly the period for release from treatment (RFT) of patients. It
is effective in inducing a fall of bacterial index (BI) in multibacillary
patients who are either nonresponders or slow responders to the standard
multidrug therapy and who have persistent BI over long periods. An
additional benefit of immunization with this vaccine is the conversion of
>60% of LL, 71% of BL and 100% of BB patients from lepromin negativity
to lepromin positivity status. A significant number of vaccinated patients
showed histopathological upgrading and eventually attainment of a state of
nonspecific infiltration without dermal granulomas. The vaccine was well
tolerated and the incidence of Type 2 reactions and their severity was
less in combined immuno cum chemotherapy group than in the group receiving
only chemotherapy. This review describes the nature of the vaccine and the
way it was developed.
=========================================================================
56.) Protective effect of Bacillus Calmette Guerin (BCG) against leprosy:
a population-based case-control study in Nagpur, India.
=========================================================================
Lepr Rev 1999 Sep;70(3):287-94
Zodpey SP, Bansod BS, Shrikhande SN, Maldhure BR, Kulkarni SW
Clinical Epidemiology Unit, Govt Medical College, Nagpur, MS, India.
A population-based pair-matched case-control study was carried out in an
urban community, Nagpur, India, to estimate the effectiveness of BCG
vaccination in the prevention of leprosy. The study included 212 cases of
leprosy (diagnosed by WHO criteria), below the age of 35 years, detected
during a leprosy survey conducted by the Government of Maharashtra over a
population of 20,03,325. Each case was pair-matched with one neighbourhood
control for age, sex and socioeconomic status. A significant protective
association between BCG and leprosy was observed (OR = 0.40, 95% CI =
0.23-0.68). The overall vaccine effectiveness (VE) was estimated to be 60%
(95% CI = 32-77). The BCG effectiveness against multi-bacillary and
paucibacillary leprosy was 72% (95% CI = 35-88) and 45% (95% CI = 3-73),
respectively. Vaccine was more effective during the first decade of life,
among females and in lower socioeconomic strata. The overall prevented
fraction was 39% (95% CI = 16-58). In conclusion, this first ever
population-based case control study performed in Central India, identified
a beneficial role of BCG vaccination in prevention of leprosy in study
population.
=========================================================================
57.) The antigen 85 complex vaccine against experimental Mycobacterium
leprae infection in mice.
=========================================================================
Vaccine 1999 Dec 10;18(9-10):795-8
Naito M, Matsuoka M, Ohara N, Nomaguchi H, Yamada T
Department of Oral Bacteriology, Nagasaki University School of Dentistry,
Sakamoto 1-7-1, Nagasaki, Japan.
The proteins in culture filtrate derived from Bacillus Calmette-Guerin
(BCG) were examined for protection against infection by Mycobacterium
leprae. Immunization with the major secreted proteins, antigen 85 complex
(Ag 85) A, B and C, induced effective protective immunity against
multiplication of M. leprae in the foot pads of mice. The most effective
protection was observed when mice were immunized with Ag 85A. A single
immunization with Ag 85 could induce antigen-specific interferon gamma
(IFNgamma) synthesis and more effective protection than live BCG vaccine.
This study demonstrates that Ag 85 is an important immunoprotective
molecule against leprosy infection.
=========================================================================
58.) Induction of lepromin positivity following immuno-chemotherapy with
Mycobacterium w vaccine and multidrug therapy and its impact on
bacteriological clearance in multibacillary leprosy: report on a
hospital-based clinical trial with the candidate antileprosy vaccine.
=========================================================================
Int J Lepr Other Mycobact Dis 1999 Sep;67(3):259-69
Sharma P, Kar HK, Misra RS, Mukherjee A, Kaur H, Mukherjee R, Rani R
National Institute of Immunology, New Delhi, India.
A vaccine based on autoclaved Mycobacterium w was administered, in
addition to standard multidrug therapy (MDT), to 157 bacteriologically
positive, lepromin-negative, multibacillary (LL, BL and BB) leprosy
patients. The vaccinees were supported by a well-matched control group of
147 patients with similar type of disease who received a placebo injection
in addition to MDT. The MDT was given for a minimum period of 2 years and
continued until skin-smear negativity, while the vaccine was given at
3-month intervals up to a maximum of 8 doses. The lepromin response
evaluated in terms of percentage of subjects converting to positivity
status, measurement in millimeters, and duration of lepromin positivity
sustained, reflected a statistically significant better outcome in the
vaccine group patients (especially LL and BL leprosy) in comparison to
those in the placebo group. The data indicate that lepromin-positivity
status seems to have an impact on accelerating the bacteriological
clearance, as is evident by the statistically significant accelerated
decline in the BI of those patients who converted to lepromin positivity
as compared to those remaining lepromin negative throughout therapy and
post-therapy follow up. To conclude, the addition of the Mycobacterium w
vaccine to standard MDT induces a lepromin response of a statistically
significant higher magnitude than that observed with MDT alone.
=========================================================================
59.) Disabilities in multibacillary leprosy following multidrug therapy
with and without immunotherapy with Mycobacterium w antileprosy vaccine.
=========================================================================
Int J Lepr Other Mycobact Dis 1999 Sep;67(3):250-8
Sharma P, Kar HK, Misra RS, Mukherjee A, Kaur H, Mukherjee R, Rani R
National Institute of Immunology, New Delhi, India. rajni@nii.res.in
A vaccine based on autoclaved Mycobacterium w was administered, in addition to standard multidrug therapy (MDT), to 157 bacteriologically positive, lepromin-negative, multibacillary leprosy patients supported by a well-matched control group of 147 patients with similar type of disease who received a placebo injection in addition to MDT. The MDT was given for a minimum period of 2 years and continued until skin-smear negativity, while the vaccine/placebo was given at 3-month intervals up to a maximum of 8 doses in the initial 2 years. The overall incidence of type 1 and type 2 reactions and neuritis during treatment and follow up was nearly equal in the patients in the vaccine and placebo groups; the differences were not statistically significant. The occurrence of disabilities, such as anesthesia, trophic ulcers, claw hand and grade 3 deformities, were not different statistically in the vaccine and placebo groups, an observation valid both for deformities present at induction and for those which developed during the course of therapy and surveillance. A statistically significant difference was observed in the recovery of newly developed trophic ulcers; recovery was quicker in the vaccine group. The recovery rate for motor deformities was marginally higher in the vaccine group, although not significant (p = 0.068) statistically. There was a statistically significant reduction in the incidence of grade 3 deformities following MDT with and without immunotherapy. To conclude, the addition of vaccine to MDT did not precipitate neuritis or deformities over and above that encountered with MDT alone, although it did accelerate bacteriological clearance, histopathological upgrading, conversion to lepromin positivity, and clinical improvement.
=========================================================================
60.) SIMLEP: a simulation model for leprosy transmission and control.
=========================================================================
Int J Lepr Other Mycobact Dis 1999 Sep;67(3):215-36
Meima A, Gupte MD, van Oortmarssen GJ, Habbema JD
Department of Public Health, Faculty of Medicine, Erasmus University
Rotterdam, The Netherlands. Meima@mgz.fgg.eur.nl
SIMLEP is a computer program for modeling the transmission and control of
leprosy which can be used to project epidemiologic trends over time,
producing output on indicators such as prevalence, incidence and
case-detection rates of leprosy. In SIMLEP, health states have been
defined that represent immunologic conditions and stages of leprosy
infection and disease. Three types of interventions are incorporated:
vaccination, case detection and chemotherapy treatment. Uncertainties
about leprosy have led to a flexible design in which the user chooses
which of many aspects should be included in the model. These aspects
include natural immunity, asymptomatic infection, type distribution of new
cases, delay between onset of disease and start of chemotherapy, and
mechanisms for leprosy transmission. An example run illustrates input and
output of the program. The output produced by SIMLEP can be readily
compared with observed data, which allows for validation studies. The
support that SIMLEP can give to health policy research and actual decision
making will depend upon the extent of validation that has been achieved.
SIMLEP can be used to improve the understanding of observed leprosy
trends, for example, in relation to early detection campaigns and the use
of multidrug therapy, by exploring which combinations of assumptions can
explain these trends. In addition, SIMLEP allows for scenario analysis in
which the effects of control strategies combining different interventions
can be simulated and evaluated.
=========================================================================
61.) Antigenic definition of plasma membrane proteins of Bacillus
Calmette-Guerin: predominant activation of human T cells by
low-molecular-mass integral proteins.
=========================================================================
Scand J Immunol 1999 Oct;50(4):411-9
Mehrotra J, Mittal A, Rastogi AK, Jaiswal AK, Bhandari NK, Sinha S
Division of Membrane Biology, Central Drug Research Institute, Lucknow,
India.
Mycobacterial plasma membrane proteins, in particular the
detergent-soluble or 'integral' ones, comprise a class of mostly
unexplored antigens capable of inducing potent activation of human T
cells. Plasma membrane isolated from culture-grown Bacillus
Calmette-Guerin (BCG; Indian vaccine; Danish strain) was subjected to a
Triton X-114-based biphasic extraction procedure for isolation of
peripheral (water-soluble) and integral proteins (PMP and IMP). A
distinction between the two protein pools was evident from results of
SDS-PAGE and immunoblotting using antisera raised in rabbits. An
enzyme-linked immunosorbant assay with a panel of WHO-IMMYC monoclonal
antibodies against various mycobacterial antigens revealed that three
well-known antigens, 19 kDa, 33/36 kDa (proline rich) and 38 kDa (PstS
homologue), were part of the IMP pool; and another such antigen, 14/16 kDa
alpha-crystallin homologue, partly constituted the PMP pool. Apparently,
antigenically distinct species of the immunomodulatory moiety
lipoarabinomannan partitioned in aqueous and detergent phases. Human
T-cell proliferation assays in donors comprising tuberculoid leprosy and
pulmonary tuberculosis patients and healthy BCG vaccinees showed
significantly greater potency of IMP over PMP and this immunodominance
appeared to be directed towards CD4+ cells. IMP of < 56 kDa were
resolved by 'continuous elution SDS-PAGE' into 15 fractions which, after
extraction of SDS, were used in T-cell proliferation assays for the
identification of immunodominant constituents. Proteins falling within
three low-molecular-mass zones (all < 35 kDa) performed better than the
rest, particularly a approximately 22 kDa fraction, which strongly
stimulated T cells from all five donors. Partial overlap between IMP and
secreted proteins, as noticed in this study, could provide clues to
immunodominance of the latter. The apparent uniqueness and a high T-cell
activating potency make mycobacterial IMP attractive candidates for
designing future vaccines or immunotherapeutic agents.
=========================================================================
62.) A lost talisman: catastrophic decline in yields of leprosy bacilli
from armadillos used for vaccine production.
=========================================================================
Int J Lepr Other Mycobact Dis 1999 Mar;67(1):67-70
Storrs EE
Publication Types:
Letter
=========================================================================
=========================================================================
63.) HLA-DRB1 leprogenic motifs in nigerian population groups.
=========================================================================
Clin Exp Immunol 1999 Oct;118(1):56-62
Uko GP, Lu LY, Asuquo MA, Fici D, Mahan S, Awdeh Z, Udim ER, Ding W, Umana
U, Adewole T, Fraser PA
The Nigerian Institute of Medical Research, Yaba, Lagos, Nigeria.
Amino acid residues involved in the peptide binding groove of HLA-DRB1
alleles were examined in three Nigerian ethnic groups with leprosy (n =
287) and 170 controls to determine the role of DRB1 alleles in disease
outcome with Mycobacterium leprae. Nine positively charged motifs and two
others with neutral charge to the binding groove were detected. These
motifs occurred more frequently in leprosy (leprogenic) than was expected
by chance (P < 0.0001). In contrast, five motifs with net negative or
'modified' neutral charges to the pocket were negatively associated with
leprosy. We conclude that clinical outcome of infection with M. leprae is
largely determined by a shared epitope in DRB1 alleles marked by several
motifs. These motifs occur in otherwise normal DRB1 alleles, characterized
by net positive or neutral charges in the binding groove. We hypothesize
that these polarities cause poor binding of DRB1 to M. leprae. On
presentation, the signal via the T cell receptor results in muted
cell-mediated immunity. The resulting response translates to various forms
of leprosy depending on degree of charge consonance between M. leprae and
host DRB1 allele. Other factors within or without the HLA complex, such as
the T cell receptor repertoire, may also influence the resulting disease.
=========================================================================
64.) Testing candidate genes that may affect susceptibility to leprosy.
=========================================================================
Tissue Antigens 1998 Aug;52(2):147-52
Cervino AC, Curnow RN
Department of Applied Statistics, University of Reading, U.K.
Several statistical methods have been used to search familial data sets
for marker alleles associated with the occurrence of a disease. In the
present paper, a recently developed method is used to re-analyze published
data on leprosy and candidate genes at the HLA loci. This new method of
analysis, the randomization transmission disequilibrium test (TDT),
confirmed previous conclusions that there was no significant evidence
against random transmission at the HLA-A locus but significant positive
association with the HLA-DR2 allele. The randomization TDT detected
significant protective associations, that had not previously been found,
with alleles HLA-B8 in Egyptian families and HLA-B21 (current nomenclature
B x 4901, 5001-5002) in South Indian families, highlighting a major
advantage of permutation tests in analyzing candidate gene loci with rare
alleles. These findings provide evidence that HLA class I restricted T
lymphocytes may be of protective importance in leprosy.
=========================================================================
65.) [Leprosy, an "exemplary" humanitarian disease]?
=========================================================================
Ann Chir Plast Esthet 1999 Feb;44(1):46-55
Mole B
Leprosy still remains a dreaded disease despite the possibilities of
permanent cure, the efficacy of surgical corrections, and its forthcoming
disappearance. The authors conducted several surgical missions in
Benin-Africa--over 4 years and report an interesting rate of control in
the survey of patients as the results of their procedures were reviewed in
84% of them. Leprosy represents the perfect example of the difficulties of
any humanitarian involvement with apparent contradictions between the aims
of the medical wishes and the presence of a dreaded symbol
that--fortunately or not--allow the existence of the many associations
involved in the fight against leprosy.
=========================================================================
66.) Prediction of elimination of leprosy in leprosy endemic areas of
China.
=========================================================================
Indian J Lepr 1999 Apr-Jun;71(2):189-201
Chen XS, Li WZ, Jiang C, Ye GY
Institute of Dermatology, CAMS&PUMC National Centre for STD and
Leprosy
Control, Nanjing, China.
A study was carried out based upon the data from the National System for
Leprosy Surveillance and using appropriate mathematical models. The
results showed that of 337 counties where the national goal of basic
eradication of leprosy had not been reached and in 40 counties where the
WHO goal of leprosy elimination had not been achieved in 1996, the
detection rates in calendar years followed exponential models with
significant goodness-of-fit. In the 67 counties with downward trends of
detection rates, the national goal can be met in terms of detection rate
in 6% of counties before the year 2000 or 34.4% before the year 2010, or,
in terms of prevalence rate in 31.3% before the year 2010. In the 11
counties with downward trends of the detection rates, the WHO target can
be met in eight to ten counties within this century when the duration of
disease was determined with the WHO definition. If the MB proportion among
new cases increased by 10%, the target would be met one year later.
However, at the same MB proportion, the change of fixed treatment
schedules from PB six months and MB two years to PB nine months and MB
three years will cause achievement of the goal to be postponed by two to
ten years.
=========================================================================
67.)[Global leprosy, current status and a future outlook].
=========================================================================
Nihon Hansenbyo Gakkai Zasshi 1999 Jul;68(2):87-90
Yuasa Y
Sasakawa Memorial Health Foundation.
Successful "Leprosy Elimination Programme" since 1991 managed to reduce
global case load to nearly 1/10 in 10 years. However, this rapid fall of
case detection/incident rate. This means that even after year 2,000,
control effort of leprosy as an infectious disease must be sustained,
while adequate control/care of leprosy as a deformity/disability causing
disease need more attention.
=========================================================================
68.) Lot quality assurance sampling (LQAS) for monitoring a leprosy
elimination program.
=========================================================================
Int J Lepr Other Mycobact Dis 1999 Jun;67(2):143-9
Gupte MD, Narasimhamurthy B
Institute for Research in Medical Statistics, Tamil Nadu, India.
In a statistical sense, prevalences of leprosy in different geographical
areas can be called very low or rare. Conventional survey methods to
monitor leprosy control programs, therefore, need large sample sizes, are
expensive, and are time-consuming. Further, with the lowering of
prevalence to the near-desired target level, 1 case per 10,000 population
at national or subnational levels, the program administrator's concern
will be shifted to smaller areas, e.g., districts, for assessment and, if
needed, for necessary interventions. In this paper, Lot Quality Assurance
Sampling (LQAS), a quality control tool in industry, is proposed to
identify districts/regions having a prevalence of leprosy at or above a
certain target level, e.g., 1 in 10,000. This technique can also be
considered for identifying districts/regions at or below the target level
of 1 per 10,000, i.e., areas where the elimination level is attained. For
simulating various situations and strategies, a hypothetical computerized
population of 10 million persons was created. This population mimics the
actual population in terms of the empirical information on rural/urban
distributions and the distribution of households by size for the state of
Tamil Nadu, India. Various levels with respect to leprosy prevalence are
created using this population. The distribution of the number of cases in
the population was expected to follow the Poisson process, and this was
also confirmed by examination. Sample sizes and corresponding critical
values were computed using Poisson approximation. Initially,
villages/towns are selected from the population and from each selected
village/town households are selected using systematic sampling. Households
instead of individuals are used as sampling units. This sampling procedure
was simulated 1000 times in the computer from the base population. The
results in four different prevalence situations meet the required limits
of Type I error of 5% and 90% Power. It is concluded that after validation
under field conditions, this method can be considered for a rapid
assessment of the leprosy situation.
=========================================================================
69.) Patient contact is the major determinant in incident leprosy:
implications for future control.
=========================================================================
Int J Lepr Other Mycobact Dis 1999 Jun;67(2):119-28
van Beers SM, Hatta M, Klatser PR
Department of Biomedical Research, Royal Tropical Institute, Amsterdam,
The Netherlands.
Notwithstanding the elimination efforts, leprosy control programs face the
problem of many leprosy patients remaining undetected. Leprosy control
focuses on early diagnosis through screening of household contacts,
although this high-risk group generates only a small proportion of all
incident cases. For the remaining incident cases, leprosy control programs
have to rely on self-reporting of patients. We explored the extent to
which other contact groups contribute to incident leprosy. We examined
retrospectively incident leprosy over 25 years in a high-endemic village
of 2283 inhabitants in Sulawesi, Indonesia, by systematically reviewing
data obtained from the local program and actively gathering data through
interviews and a house-to-house survey. We investigated the contact status
in the past of every incident case. In addition to household contact, we
distinguished neighbor and social contacts. Of the 101 incident cases over
a 25-year period, 79 (78%) could be associated to contact with another
leprosy patient. Twenty-eight (28%) of these 101 cases were identified as
household contacts, 36 (36%) as neighbors, and the remaining 15 (15%) as
social contacts. Three patients had not had a traceable previous contact
with another leprosy patient, and no information could be gathered from 19
patients. The median span of time from the registration of the primary
case to that of the secondary case was 3 years; 95% of the secondary cases
were detected within 6 years after the primary case. The estimated risk
for leprosy was about nine times higher in households of patients and four
times higher in direct neighboring houses of patients compared to
households that had had no such contact with patients. The highest risk of
leprosy was associated with households of multibacillary patients. The
risk of leprosy for households of paucibacillary patients was similar to
the risk of leprosy for direct neighboring houses of multibacillary
patients, indicating that both the type of leprosy of the primary case and
the distance to the primary case are important contributing factors for
the risk of leprosy. Contact with a leprosy patient is the major
determinant in incident leprosy; the type of contact is not limited to
household relationships but also includes neighbor and social
relationships. This finding can be translated into a valuable and
sustainable tool for leprosy control programs and elimination campaigns by
focusing case detection and health promotion activities not only on
household contacts but also on at least the neighbors of leprosy cases.
=========================================================================
70.) A continuing focus of Hansen's disease in Texas.
=========================================================================
Am J Trop Med Hyg 1999 Mar;60(3):449-52
Taylor JP, Vitek I, Enriquez V, Smedley JW
Tuberculosis Elimination Division and Hansen's Disease Program, Texas
Department of Health, Austin 78756, USA.
To describe epidemiologic and clinical characteristics of Hansen's disease
cases in Texas, information was abstracted from records of 810 patients
reported from 1973 through 1997. Annually, from 18 to 54 patients were
reported. Average annual incidence rates ranged from 1.9 to 2.4 cases per
million population. A majority of the patients were male (63%) and white
(77%). More than half (53%) of the patients were born in the United
States; a majority (83%) of the patients born in the United States were
born in Texas. Most (76%) patients were diagnosed with multi-bacillary
leprosy. Foreign-born patients were more likely to be younger at onset and
have multi-bacillary disease compared with patients born in the United
States. Within Texas, an endemic focus of Hansen's disease exists along
the Gulf of Mexico coast.
=========================================================================
71.) An epidemiological study on Mycobacterium leprae infection and
prevalence of leprosy in endemic villages by molecular biological
technique.
=========================================================================
Indian J Lepr 1999 Jan-Mar;71(1):37-43
Izumi S, Budiawan T, Saeki K, Matsuoka M, Kawatsu K
Ternate Leprosy Hospital, Maluku, Indonesia.
One of the most important unsolved questions in epidemiology of leprosy is
the highly uneven geographic distribution of the disease. There are many
hyperendemic "pockets" in endemic countries. Little is known about the
reasons why leprosy is hyperendemic in these areas. We conducted,
therefore, a series of epidemiological studies on Mycobacterium leprae
infection and prevalence of leprosy in North Maluku district, Maluku
Province, Indonesia where leprosy is highly endemic. It was found that
considerable number of general inhabitants are seropositive to various
mycobacterial antigens and 27% of the villagers were carrying leprosy
bacilli on their surface of nasal cavity. These results suggested the
importance of M. leprae in the residential environment in infection of the
leprosy bacillus and the resulting transmission of the disease. Based on
these observations, we conclude that new preventive measures are essential
for global elimination of leprosy in addition to early diagnosis and
multidrug therapy (MDT).
=========================================================================
72.) Antimycobacterial activities of riminophenazines.
=========================================================================
J Antimicrob Chemother 1999 May;43(5):615-23
Reddy VM, O'Sullivan JF, Gangadharam PR
Department of Biomedical Sciences, UIC College of Medicine at Rockford, IL
61107, USA.
Riminophenazines were specifically developed as drugs active against
Mycobacterium tuberculosis but extensive research over several decades has
shown that these compounds are also active against many other
mycobacterial infections, particularly those caused by Mycobacterium
leprae and the Mycobacterium avium complex (MAC). Clofazimine, the lead
compound in this series, is included in the regimens that are approved by
the WHO for the treatment of leprosy and has contributed significantly to
the control of that disease, particularly that caused by dapsone-resistant
bacteria. Despite early problems, clofazimine has shown clinical efficacy
in tuberculosis, in particular that caused by multiple drug resistant
strains. Clofazimine does not induce resistance and also inhibits
emergence of resistance to isoniazid in M. tuberculosis. The efficacy of
clofazimine against MAC is more varied and the availability of better
drugs has limited its use. Newer riminophenazines, such as B746 and B4157,
not only showed increased anti-mycobacterial activity but also produced
less skin pigmentation, which is the main drawback of this group of
compounds. The most important virtues of riminophenazines, such as
intracellular accumulation in mononuclear phagocytic cells,
anti-inflammatory activity, a low incidence of drug resistance and slow
metabolic elimination, make them attractive candidates for the treatment
of mycobacterial infections. It is essential, however, to investigate the
newer analogues clinically, while continuing the pursuit of alternate
candidates that demonstrate higher anti-mycobacterial activity and lower
rates of skin pigmentation.
=========================================================================
73.) Nasal mucosa and skin of smear-positive leprosy patients after 24
months of fixed duration MDT: histopathological and microbiological study.
=========================================================================
Int J Lepr Other Mycobact Dis 1999 Sep;67(3):292-7
Ebenezer GJ, Job A, Abraham S, Arunthathi S, Rao PS, Job CK
Department of Histopathology and Experimental Pathology, Schieffelin
Leprosy Research and Training Center, Tamil Nadu, India.
The skin and nasal mucosa of 10 lepromatous leprosy patients who had
completed 24 doses of fixed duration multidrug therapy (MDT) but who
continued to be skin-smear positive for acid-fast bacilli (AFB) were
examined histopathologically. The nasal mucosa showed granuloma fractions
that exceeded those seen in the skin specimens, signifying that activity
in this region subsides much more gradually than the activity in the skin.
Mouse foot pad studies done using T900r mice with an inoculum from the
nasal mucosa biopsy specimens of these patients did not demonstrate any
growth of Mycobacterium leprae, indicating that these bacilli were not
viable. A skin specimen from one patient grew significant amounts of
bacteria in the T900r mouse foot pad. These results show that 2 years of
treatment with MDT would prevent dissemination of M. leprae from the nasal
mucosa and, therefore, should preclude further transmission of the
disease. It also indicates that viable bacteria might persist in the skin
of patients, especially those with an initial bacterial index of > or =
4+ who have completed 24 doses of regular MDT. Therefore, a more cautious
approach to administering only 12 doses of MDT to highly positive
multibacillary patients is suggested.
=========================================================================
74.) Resolution of lepromatous leprosy after a short course of
amoxicillin/clavulanic acid, followed by ofloxacin and clofazimine.
=========================================================================
Int J Dermatol 1999 Jul;38(7):558-60
Villahermosa LG, Walsh DS, Fajardo TT Jr, Abalos RM, dela Cruz EC,
Veerasubramanian P, Walsh GP Publication Types:
letter
=========================================================================
=========================================================================
75.) Effect of zafirlukast on leprosy reactions.
=========================================================================
Int J Lepr Other Mycobact Dis 1999 Mar;67(1):71-5
Vides EA, Cabrera A, Ahern KP, Levis WR
Publication Types:
Clinical trial
Clinical trial, phase ii
Letter
=========================================================================
=========================================================================
76.) Immunochemotherapy with interferon-gamma and multidrug therapy for
multibacillary leprosy.
=========================================================================
Acta Trop 1999 Mar 15;72(2):185-201
Barral-Netto M, Santos S, Santos I, von Sohsten R, Bittencourt AL,
Carvalho
EM, Barral A, Waters M
Servico de Immunologia HUPES, Universidade Federal da Bahia, Brazil.
barral@svn.com.br
Treatment for multibacillary leprosy is presently performed with a
multidrug therapy (MDT) scheme maintained for 2 years. Leprosy treatment
however can benefit from the reduction of length. The lack of
interferon-gamma (IFN-gamma) production by lepromatous leprosy (LL)
patients' lymphocytes lead us to use this cytokine in the treatment of
multibacillary leprosy associated with MDT in the treatment of
multibacillary leprosy, and monitor several clinical and immunological
parameters during the course of treatment. A total of 20 multibacillary
leprosy patients were evaluated, 10 treated with MDT alone, and 10 treated
with MDT + 10 daily doses of 2 x 10(6) international units (IU) of
recombinant human IFN-gamma/m2 followed by 10 daily doses of 10(7) IU
IFN-gamma/m2, intramuscularly, during the first 20 days of MDT. IFN-gamma
was well tolerated and did not cause any increase in the rate of leprosy
reactions development during treatment. Decrease of bacillary load, fall
of anti-Mycobacterium leprae IgG serum antibodies, changes of histological
pattern, as well as changes in lymphocyte proliferation assay in response
to mitogens (PHA or PWM), M. leprae antigen or PPD was similar in both
groups of patients. Among several soluble immunological markers measured
before and 30 days after beginning of treatment, levels of soluble IL-2R
receptor increased in patients treated with MDT plus IFN-gamma whereas
decreased in patients treated with MDT alone. Soluble ICAM-1 levels
decreased in the MDT group but did not change in the MDT + IFN-gamma
treated patients. Soluble CD4 and soluble CD8 markers did not change
significantly in either group of patients. Neopterin, a marker of
macrophage activation, increased in all but one patient treated with MDT +
IFN-gamma but in none treated with MDT alone, indicating that IFN-gamma
was active in vivo. Our findings indicate that despite being able to
promote macrophage activation in multibacillary leprosy patients a short
course of systemically administered IFN-gamma is not able to change the
clinical course of a long standing disease such as leprosy.
===================================================================
77.) Thalidomide's effectiveness in erythema nodosum leprosum is
associated with a decrease in CD4+ cells in the peripheral blood.
===================================================================
SO - Lepr Rev 1992 Mar;63(1):5-11
AU - Shannon EJ; Ejigu M; Haile-Mariam HS; Berhan TY; Tasesse G
AD - Pharmacology Research Department, G.W. Long Hansen's Disease Center,
Carville, La 70721.
MJ - CD4-CD8 Ratio; Erythema Nodosum [drug therapy]; Leprosy, Lepromatous
[drug therapy]; Thalidomide [therapeutic use]
MN - Adult; Erythema Nodosum [immunology]; Leprosy, Lepromatous
[immunology]
MT - Human; Male; Support, Non-U.S. Gov't
PT - JOURNAL ARTICLE
AB - Thalidomide is well documented as being an effective drug in the
treatment of erythema nodosum leprosum (ENL). The mechanism of action of
thalidomide in ENL as well as the pathogenesis of ENL are yet to be fully
determined. Lepromatous leprosy patients experiencing ENL have been
reported to have an increase in the ratio of CD4+ to CD8+ cells in their
blood and ENL skin lesions. Thalidomide has been shown to cause a decrease
in the ratio of CD4+ to CD8+ lymphocytes in the blood of healthy males.
This decrease was due to a significant reduction in the numbers of Cd4+
lymphocytes and an apparent increase in the numbers of CD8+ lymphocytes.
In this study, thalidomide's effectiveness in halting chronic ENL and
arresting a relapse into ENL was consistently associated with a decrease
in the numbers of CD4+ lymphocytes in the blood of 2 male lepromatous
leprosy patients.
===================================================================
78.) La lepra, Evolucion Historia, epidemiologica y medidas de control.
Autor: Zulueta R, Ana M
Dermatologia Venezolana, Vol. 2 No. 4, 1.992
===================================================================
79.) Leprosy in infants.
===================================================================
Baker B. et al.
In J leprosy 53:517-23
===================================================================
===================================================================
80.) Leprosy in a child of less than two months of age.
===================================================================
Benerjee, K, Meyers W.M.,
Clinical Dermatology, The CMD Case collection, World Congress Of
Dermatology
Berlin (West),
May 24-29-1.987,: 149.
History. Patient was a less than 2 months oid male baby belonging to one
of the trained nurses of our Institute. The chud had close, intimate
contact with a relative who suffered from dimorphous leprosy and who had
taken treatment for only 6 months before discontinuing it on his own.
Examination. A round, elevated, red-dish lesion was detected on the face
(see attach). Investigations. KOH mount of scrap-ings showed no fungus. A
slit smear for acid fast bacilli was negative. Histopathology. Skin biopsy
material was sent to 4 different centres. Ah of them confirmed it to be
Hansen's disease of a tuberculoid nature. Treatment. The lesion resolved
com-pletely within three months' treatment with D.D.S. 2.5 mg for 5 days
each week. Conclusion. To my knowledge leprosy at less than 2 months of
age has not yet been reported and may be disputed. Two cases of leprosy at
6 months of age were reported by Bruce Baker et al. The precise mode of
natural transmission, the incuba-tion period and clinical manifestation
have not yet been established. Early signs and diagnosis may be missed in
the mistaken belief that leprosy is non-existent in the very young.
==================================================
81.) Spatial clustering and local risk of leprosy in São Paulo, Brazil.
==================================================
PLoS Negl Trop Dis. 2017 Feb 27;11(2):e0005381. doi:
10.1371/journal.pntd.0005381. [Epub ahead of print]
Ramos AC1, Yamamura M2, Arroyo LH1, Popolin MP1, Chiaravalloti Neto F3,
Palha PF4, Uchoa SA5, Pieri
FM6, Pinto IC4, Fiorati RC7, Queiroz AA2, Belchior AS2, Dos Santos DT2,
Garcia MC2, Crispim JA1, Alves LS1, Berra TZ1, Arcêncio RA4.
Author information
1Graduate Program in Public Health Nursing, University of São Paulo at
Ribeirão Preto College of Nursing, Ribeirão Preto, São Paulo, Brazil.
2Graduate Program Interunit Doctoral Program in Nursing, University of São
Paulo at Ribeirão Preto College of Nursing, Ribeirão Preto, São Paulo,
Brazil.
3Department of Epidemiology, School of Public Health of the University of
São Paulo, São Paulo, São Paulo, Brazil.
4Maternal-Infant Nursing and Public Health Department, University of São
Paulo at Ribeirão Preto College of Nursing, Ribeirão Preto, São Paulo,
Brazil.
5Department of Public Health, Federal University of Rio Grande do Norte,
Natal, Rio Grande do Norte, Brazil.
6Department of Nursing, Londrina State University, Londrina, Paraná,
Brazil.
7Department of Neurosciences and Behavioral Sciences, Ribeirão Preto
Medical School of the University of São Paulo, Ribeirão Preto, São Paulo,
Brazil.
Abstract
BACKGROUND:
Although the detection rate is decreasing, the proportion of new cases
with WHO grade 2 disability (G2D) is increasing, creating concern among
policy makers and the Brazilian government. This study aimed to identify
spatial clustering of leprosy and classify high-risk areas in a major
leprosy cluster using the SatScan method. METHODS:
Data were obtained including all leprosy cases diagnosed between January
2006 and December 2013. In addition to the clinical variable, information
was also gathered regarding the G2D of the patient at diagnosis and after
treatment. The Scan Spatial statistic test, developed by Kulldorff e
Nagarwalla, was used to identify spatial clustering and to measure the
local risk (Relative Risk-RR) of leprosy. Maps considering these risks and
their confidence intervals were constructed.
RESULTS:
A total of 434 cases were identified, including 188 (43.31%) borderline
leprosy and 101 (23.28%) lepromatous leprosy cases. There was a
predominance of males, with ages ranging from 15 to 59 years, and 51
patients (11.75%) presented G2D. Two significant spatial clusters and
three significant spatial-temporal clusters were also observed. The main
spatial cluster (p = 0.000) contained 90 census tracts, a population of
approximately 58,438 inhabitants, detection rate of 22.6 cases per 100,000
people and RR of approximately 3.41 (95%CI = 2.721-4.267). Regarding the
spatial-temporal clusters, two clusters were observed, with RR ranging
between 24.35 (95%CI = 11.133-52.984) and 15.24 (95%CI =
10.114-22.919).
CONCLUSION:
These findings could contribute to improvements in policies and
programming, aiming for the eradication of leprosy in Brazil. The Spatial
Scan statistic test was found to be an interesting resource for health
managers and healthcare professionals to map the vulnerability of areas in
terms of leprosy transmission risk and areas of underreporting.
===================================================
82.) Unexpectedly high leprosy seroprevalence detected using a random
surveillance strategy in midwestern Brazil: A comparison of ELISA and a
rapid diagnostic test.
===================================================
PLoS Negl Trop Dis. 2017 Feb 23;11(2):e0005375. doi:
10.1371/journal.pntd.0005375. [Epub ahead of print]
Frade MA1, de Paula NA1, Gomes CM1,2, Vernal S1, Bernardes Filho F1, Lugão
HB1, de Abreu MM3, Botini P3, Duthie MS4, Spencer JS5, Soares RC6, Foss
NT1.
Author information
1Dermatology Division, Department of Medical Clinics, Ribeirao Preto
Medical School, University of São Paulo, Ribeirão Preto, Brazil.
2Dermatology Division, Department of Medical Clinics, Faculty of Medicine,
University of Brasília, Brasília, Brazil.
3Service of Dermatology, University of Oeste Paulista, Presidente
Prudente, Brazil.
4Infectious Diseases Research Institute, 1616 Eastlake Av. E, Seattle, WA,
United States of America.
5Colorado State University, Department of Microbiology, Immunology and
Pathology, Fort Collins, CO, United States of America.
6General Coordination of Leprosy and Eliminating Diseases, Surveillance
Secretariat in Health, Brazilian Health Ministry, Brasília, Distrito
Federal, Brazil.
Abstract
BACKGROUND:
Leprosy diagnosis is mainly based on clinical evaluation, although this
approach is difficult, especially for untrained physicians. We conducted a
temporary campaign to detect previously unknown leprosy cases in
midwestern Brazil and to compare the performance of different serological
tests.
METHODS:
A mobile clinic was stationed at the main bus terminal in Brasília,
Brazil. Volunteers were quizzed and given a clinical exam to allow
categorization as either patients, known contacts of patients or
non-contacts, and blood was collected to determine anti-PGL-I and
anti-LID-1 antibody titers by ELISA and by the NDO-LID rapid test. New
cases of leprosy and the impact of performing this broad random
surveillance strategy were evaluated. Accuracy values and concordance
between the test results were evaluated among all groups.
RESULTS:
Four hundred thirty-four individuals were evaluated, and 44 (10.1%) were
diagnosed with leprosy. Borderline forms were the most frequent
presentation. Both tests presented higher positivity in those individuals
with multibacillary disease. All tests demonstrated a specificity of
approximately 90% but only a sensitivity for clinical disease of less than
20%. A substantial agreement between NDO-LID and ELISA with concomitant
positive results was found within leprosy patients (Kappa index = 0.79
CI95% 0.36-1.22).
CONCLUSIONS:
The unexpectedly high leprosy prevalence in this population indicates
ongoing community-based exposure to Mycobacterium leprae antigens and high
rates of subclinical infection. All tests showed high specificity but low
sensitivity and therefore cannot be considered for use as stand-alone
diagnostics. Rather, considering their positivity among MB patients and
non-patients, these tests can be considered effective tools for screening
and identifying individuals at high risk who might benefit from regular
monitoring.
================================================
83.) Cojedes: a leprosy hyperendemic state. (VENEZUELA)
===============================================
Aranzazu N1, Parra JJ, Cardenas M, Rada E, Zerpa O, Rivera T, Borges R,
Gonzalez P, Morales J, Sosa R, Sanchez F, Convit J.
Author information
1Instituto de Biomedicina, Ministerio del Poder Popular para Salud,
Universidad Central de Venezuela, Caracas, Venezuela. nacarida2@yahoo.es
Abstract
BACKGROUND:
Leprosy is a chronic infectious disease produced by Mycobacterium leprae.
In 1997 Venezuela reached the goal of elimination of leprosy as a public
health problem (according to the World Health Organization a prevalence
rate of ≤ 1/10,000 inhabitants), but five states still had prevalence
rates over that goal. For this study we selected Cojedes State, where
prevalence rates remain over the elimination goal.
OBJECTIVE:
Evaluate the real leprosy situation in high-prevalence areas of Cojedes
State.
MATERIALS AND METHODS:
Seven communities of Cojedes State were selected because they had the
highest historic prevalence, as well as the highest prevalence in the year
to be studied (1997).
RESULTS:
A rank correlation using Spearman's test comparing historical prevalence
rates (1946-1996) and detection rates (1998-2004) gave a statistically
significant P < 0.05 value. Diagnosed leprosy cases were as follows:
age: 3.2% under 15 years old; sex: male/female rates between 60% and
91.66% males. The highest number of cases were paucibacillary forms:
indeterminate leprosy (33.07%) and borderline tuberculoid leprosy
(32.28%); tuberculoid leprosy (7.00%); and multibacillary cases
(lepromatous leprosy, LL) were only 2.36%. Bacteriologically, 18.52
patients were M. leprae positive. At the moment of diagnosis, 96.6% showed
no disabilities, 3.4% showed grade I disabilities, and there were no grade
II or III disabilities.
CONCLUSION: This study confirms that several communities in Cojedes State
have extremely high leprosy rates.
=======================================================
84.) Seguimiento serológico de las respuestas de IgG frente a proteínas
micobacterianas recombinantes ML0405, ML2331 y LID-1 en un área
hiperendémica de lepra en Venezuela.
Portuguesa state (VENEZUELA).
========================================================
Mem Inst Oswaldo Cruz. 2012 Dec; 107 Suppl 1: 90-4.
Rada E 1 , Duthie MS , Reed SG , Aranzazu N , Convit J.
Información del autor
1 Instituto de Biomedicina, Caracas, Venezuela. Elsa.rada@gmail.com
Abstracto
La lepra es una enfermedad de evolución lenta que ocurre principalmente en
adultos. En este estudio se seleccionó la Aldea Mamaría, Estado de
Portuguesa, por tener una de las tasas de prevalencia más altas (13,25%)
de casos de lepra en 1997. Entre 1998-2004, el 20,2% de los 89 casos
registrados en esta aldea fueron menores de 15 años y 61,8% eran varones.
Las lesiones paucibacilares (PB) fueron las formas clínicas predominantes
identificadas, aunque también se encontraron formas multibacilares (MB).
Además, el 76% de los pacientes fueron bacteriológicamente negativos. En
el momento del diagnóstico, el 75% de los pacientes presentaron
discapacidad de grado 0, el 23% de grado 1 y el 2% de grado 2. Se tomaron
muestras de suero de 18 PB y 15 MB, además de 14 contactos familiares,
Inicio y fin del tratamiento. Todos los grupos fueron reevaluados durante
un período de tres años (2008-2011). Las proteínas utilizadas para la
evaluación fueron ML0405, ML2331 y LID-1. Estas proteínas micobacterianas
fueron altamente específicas para Mycobacterium leprae y las respuestas de
IgG disminuyeron tanto en pacientes MB como PB durante el tratamiento con
múltiples fármacos. Nuestros resultados sugieren que estos antígenos
podrían ser usados como marcadores para el tratamiento exitoso de
pacientes lepromatosos no reaccionales.
========================================================
85.) [A socioeconomic characterization of leprosy patients at the
dermatology clinic in Maracaibo, VENEZUELA: a case study]
=====================================
Cad Saude Publica. 1996 Apr;12(2):225-231.
[Article in Spanish]
Parra MC1.
Author information
1Universidad del Zulia, Maracaibo, Venezuela.
Abstract
This paper presents the socioeconomic characteristics of leprosy patients
treated at the Dermatology Clinic in Maracaibo, Venezuela (U.D.S). The
characteristics were obtained from a closed questionnaire given to 40
patients. Results indicate that this is mainly an adult male population,
with a reasonable level of schooling who both work and belong to
apparently well-established, stable family groups; their family income
levels correspond to a lower or medium-low social class groups. In
addition, the patients are mainly non-disabled, and clinical diagnoses are
mostly of the lepromatous and borderline types. Any educational program
targeting this group should take these socioeconomic characteristics into
account in defining the kind of patients who receive treatment at
U.D.S.
========================================================
86.) [The current challenge of imported leprosy in Spain: a study of 7
cases].
====================================
Actas Dermosifiliogr. 2011 Mar;102(2):106-13. doi:
10.1016/j.ad.2010.10.008. Epub 2011 Feb 22.
[Article in Spanish]
Contreras-Steyls M1, López-Navarro N, Herrera-Acosta E, Castillo R, Ruiz
del Portal G, Bosch RJ, Herrera E.
Author information
1Servicio de Dermatología, Hospital Clínico Universitario Virgen de la
Victoria, Málaga, Spain. torosmar1@hotmail.com
Abstract
BACKGROUND:
although the foci of leprosy once present in Spain are now under control
and almost inactive, isolated cases are still occasionally diagnosed.
Meanwhile, population migration has brought about an increase in the
incidence of cases corresponding to individuals from countries where
leprosy is endemic, leading to changes in the epidemiology of this
disease.
OBJECTIVES:
the aim of this paper was to describe the clinical, epidemiologic,
dermatologic, microbiologic, and therapeutic characteristics of cases of
leprosy in our department in the last 5 years.
MATERIAL AND METHODS:
we report the cases of imported leprosy seen in our department between
2004 and 2009.
RESULTS:
seven patients with leprosy (3 men and 4 women; age range, 26-80 years)
were diagnosed; 2 were cases of tuberculoid leprosy, 2 borderline
tuberculoid leprosy, and 3 indeterminate. All patients acquired the
disease in South American or South African countries, but were residing in
Spain at the time of diagnosis. One patient was a Spaniard, from Malaga,
who had worked as a missionary in Venezuela for 25 years. The presence of
the bacterium by either Ziehl-Neelsen stain or bacilloscopy could not be
demonstrated in any of the patients.
CONCLUSIONS:
we would like to draw attention to the changes we have observed in the
characteristics of cases of leprosy seen in our department, the majority
of which are imported. It is important to maintain a clinical suspicion of
leprosy in cases of granulomatous dermatitis, particularly in patients
from countries where the disease is endemic.
========================================================
87.) Leprosy trends at a tertiary care hospital in Mumbai, India, from
2008 to 2015.
=========================================================
Glob Health Action. 2016 Jan;9(1):32962. doi: 10.3402/gha.v9.32962.
Muthuvel T1, Isaakidis P2, Shewade HD3, Kattuppara L4, Singh R1,
Govindarajulu S1.
Author information
1a German Leprosy and TB Relief Association Chennai , India.
2b Médecins Sans Frontières (MSF)/Doctors Without Borders , Mumbai ,
India.
3c The Union, South East Asia Office , New Delhi , India.
4d Vimala Dermatological Centre , Mumbai , India.
Abstract
Background Leprosy remains an important cause of preventable disabilities.
After the advent of multidrug therapy, new leprosy cases have come down
dramatically. Despite this achievement, India, which contributes 60% of
the global leprosy burden, faces some challenges to eliminate the disease,
including active transmission in the community and delayed diagnosis of
leprosy patients. Objectives The objectives of the study were 1) to
determine sociodemographic and clinical characteristics of newly diagnosed
adults and children (less than 15 years) with leprosy and their trends
over time (2008-2015) and 2) to describe the profile of surgical
procedures among leprosy patients registered for reconstructive surgeries
during 2006-2015. Design Retrospective descriptive study was conducted
involving a record review of new patients with leprosy registered in
Vimala Dermatological Centre, Mumbai. Results A total of 578 new leprosy
cases were registered in the hospital during 2008-2015. There has been a
steady increase in the trend of child cases (less than 15 years)
registered in the facility (from 3% in 2008 to 18% in 2015), x 2=12.11,
p<0.01. The majority of the patients (68%) were migrants of Uttar
Pradesh and Bihar. Conclusions Targeting children and migrants and
ensuring early diagnosis and treatment initiation are essential components
for leprosy elimination in an urban metropolis in India.
========================================================
88.) Childhood leprosy: a retrospective descriptive study from Government
Medical College, Kozhikode, Kerala, India.
========================================================
Lepr Rev. 2014 Jun;85(2):100-10.
Sasidharanpillai S, Binitha MP, Riyaz N, Ambooken B, Mariyath OK, George
B, Janardhanan AK, Sherjeena PV.
Abstract
OBJECTIVE:
To assess the profile and describe the clinical presentations and
complications of childhood leprosy in a tertiary care hospital in North
Kerala, South India during 2003-2012 and to analyse any change in the
age-sex profile and the clinical pattern of leprosy in children below the
age of 15 years over the 10-year study period.
DESIGN:
A retrospective descriptive study of children less than 15 years of age
diagnosed with leprosy and registered for treatment in a tertiary care
institution from 2003 to 2012. Demographic, clinical, investigative and
treatment data were collected using a pre-set proforma.
RESULTS:
138 (12.1%) of the total 1143 leprosy cases registered for treatment
during the 10-year period were below 15 years of age. The 10-year study
period witnessed a statistically insignificant decrease in the new
childhood leprosy cases registered for treatment in our tertiary care
institution. The majority of cases belonged to the 6-12 year age group
(61.6%) with a male predominance. Borderline tuberculoid (BT) was the
commonest clinical type (65.9%) followed by indeterminate leprosy (18.8%);
101 patients required paucibacillary (PB) and 37 needed multibacillary
(MB) treatment. The number of patients requiring MB treatment showed a
statistically significant increase and there was a significant decline in
number of cases requiring PB treatment. During the entire study period no
Type 2 lepra reaction was documented in patients below Hema 15 years and
only two patients manifested Type 1 reaction. Ten (7.2%) out of the 138
patients were cases of relapse. There was a clear female predilection
among relapse cases with the majority belonging to the adolescent age.
CONCLUSIONS:
Childhood leprosy still contributes to a significant proportion of the
total case load denoting the continuing active horizontal transmission of
leprosy. The rise in number of patients with more extensive disease in the
background of declining disease prevalence is suggestive of the delay in
diagnosis and treatment. A high relapse rate noted in the present study
may be due to incorrect classification and treatment of MB as PB leprosy
which in turn might have resulted in treatment failure due to inadequate
treatment.
========================================================
89.) "I Wasted 3 Years, Thinking It's Not a Problem": Patient and Health
System Delays in Diagnosis of Leprosy in India: A Mixed-Methods Study.
=======================================================
PLoS Negl Trop Dis. 2017 Jan 12;11(1):e0005192. doi:
10.1371/journal.pntd.0005192. eCollection 2017.
Muthuvel T1, Govindarajulu S1, Isaakidis P2, Shewade HD3, Rokade V4, Singh
R1, Kamble S5.
Author information
1German Leprosy and TB Relief Association, Chennai, India.
2Médecins Sans Frontières (MSF)/Doctors Without Borders, Mumbai, India.
3International Union Against Tuberculosis and Lung Disease (The Union),
South-East Asia Office, New Delhi, India.
4Assistant Director of Health Services (Leprosy), Government of
Maharashtra, Pune, India.
5State Leprosy Officer/Joint Director of Health Services (Leprosy),
Government of Maharashtra, Pune, India.
Abstract
BACKGROUND:
Worldwide, leprosy is one of the major causes of preventable disability.
India contributes to 60% of global leprosy burden. With increasing numbers
of leprosy with grade 2 disability (visible disability) at diagnosis, we
aimed to determine risk factors associated with grade 2 disability among
new cases and explore patients and providers' perspectives into reasons
for late presentation.
METHODOLOGY/PRINCIPAL FINDINGS:
This was an explanatory mixed-methods study where the quantitative
component, a matched case-control design, was followed by a qualitative
component. A total of 70 cases (grade 2 disability) and 140 controls
(grade 0) matched for age and sex were randomly sampled from new patients
registered between January 2013-January 2015 in three districts of
Maharashtra (Mumbai, Thane and Amaravati) and interviewed using a
structured close ended questionnaire. Eight public health care providers
involved in leprosy care and 7 leprosy patients were purposively selected
(maximum variation sampling) and interviewed using a structured open-ended
interview schedule. Among cases, overall median (IQR) diagnosis delay in
months was 17.9(7-30); patient and health system delay was 7(4-16.5) and
5.5(0.9-12.5) respectively; this was significantly higher than the delay
in controls. Reasons for delayed presentation identified by the
quantitative and qualitative data were: poor awareness of leprosy
symptoms, first health care provider visited being private practitioners
who were not aware about provision of free leprosy treatment at public
health care facilities, reduced engagement and capacity of the general
health care system in leprosy control.
CONCLUSIONS:
Raising awareness in communities and health care providers regarding early
leprosy symptoms, engagement of private health care provider in early
leprosy diagnosis and increasing capacity of general health system staff,
especially targeting high endemic areas that are hotspots for leprosy
transmission may help in reducing diagnosis delays.
========================================================
90.) Minocycline successfully treats exaggerated granulomatous
hypersensitivity reaction to Mw immunotherapy.
========================================================
Dermatol Ther. 2016 Nov 28. doi: 10.1111/dth.12452. [Epub ahead of print]
Vinay K1, Narang T1, Saikia UN2, Kumaran MS1, Dogra S1.
Author information
1Department of Dermatology, Venereology and Leprology, Postgraduate
Institute of Medical Education and Research, Chandigarh, 160012, India.
2Department of Histopathology, Postgraduate Institute of Medical Education
and Research, Chandigarh, 160012, India.
Abstract
Mycobacterium W (Mw) vaccine has been found to be effective in the
treatment of leprosy and warts. Despite increasing use of Mw
immunotherapy, data on its safety is limited. We report a series of eight
patients who developed persisting injection site granulomatous reaction
following Mw immunotherapy and were successfully treated with minocycline.
Eight patients with persistent nodular swelling at the site of Mw
injections were identified. Seven of them had received Mw immunotherapy
for cutaneous warts and one for verrucous epidermal nevus. The lesions
were firm, erythematous, succulent, non-tender nodules confined to the
sites of Mw vaccine injections. In 6 of these patients nodules also
involved the previously injected areas. Skin biopsy from all patients
showed eosinophil rich inflammation admixed with histiocytes and
lymphocytes. In addition granulomas were seen in all with septal and
nodular panniculitis in four patients. Broken and granular acid-fast
bacilli were identified in two cases. All patients were treated with oral
minocycline 100 mg/day for a mean of 9 weeks and showed good clinical
response. Granulomatous reaction is a rare but significant adverse effect
of Mw immunotherapy at cosmetically and functionally imperative sites.
Oral minocycline appears to be effective therapy in this situation.
========================================================
91.) Generalized granulomatous dermatitis following Mycobacterium w (Mw)
immunotherapy in lepromatous leprosy.
========================================================
Dermatol Ther. 2016 Nov 28. doi: 10.1111/dth.12441. [Epub ahead of print]
Khullar G1, Narang T1, Nahar Saikia U2, Dogra S1.
Author information
1Department of Dermatology, Venereology and Leprology, Postgraduate
Institute of Medical Education and Research, Chandigarh, 160012, India.
2Department of Histopathology, Postgraduate Institute of Medical Education
and Research, Chandigarh, 160012, India.
Abstract
Mycobacterium w (Mw) vaccine is a heat-killed suspension derived from a
nonpathogenic, cultivable, atypical mycobacterium named Mycobacterium
indicus pranii. Mw immunotherapy has been reported to be efficacious as an
adjunct to multidrug therapy multibacillary regimen in leprosy patients
with high bacillary index. Cutaneous reactions are predominant adverse
effects associated with the administration of vaccines. Cutaneous adverse
effects ascribed to Mw vaccine are generally limited to the site of
injection. We herein describe two cases of lepromatous leprosy who
developed an unusual generalized cutaneous reaction following Mw
immunotherapy. A high index of suspicion is needed to identify such
manifestations in leprosy cases to avoid misdiagnosis of a relapse or a
reaction and for appropriate treatment.
========================================================
92.) World Leprosy Day
===========================================================
30 January 2017
Source: who
World Leprosy Day, observed on the last Sunday of January, focuses on the
target of zero cases of leprosy-related disabilities in children.
Disabilities do not occur overnight, but happen after a prolonged period
of undiagnosed disease. Early detection is key to achieve this target,
alongside scaling up interventions to prevent leprosy transmission.
Leprosy affected 212 000 more people globally in 2015. Of them 60% were in
India. The other high-burden countries were Brazil and Indonesia. Of the
new cases 8.9% were children and 6.7% presented with visible
deformities.This year, WHO urges countries to scale-up interventions with
a focus to avoid transmission of leprosy. An intensified, all-inclusive
approach can prevent thousands of infections every year.
=====================================
93.) Mutations in the drug resistance-determining region of Mycobacterium
lepromatosis isolated from leprosy patients in Mexico.
==========================================================
J Dermatol. 2016 Nov;43(11):1345-1349. doi: 10.1111/1346-8138.13483. Epub
2016 Jun 27.
Kai M1, Fafutis-Morris M2, Miyamoto Y3, Mukai T3, Mayorga-Rodriguez J2,
Rodriguez-Castellanos MA2, Martínez-Guzman MA2, Matsuoka M3.
Author information
1Department of Mycobacteriology, Leprosy Research Center, National
Institute of Infectious Diseases, Tokyo, Japan. mkai@nih.go.jp.
2University of Guadalajara/Instituto Dermatologico de Jalisco,
Guadalajara, Jalisco, Mexico.
3Department of Mycobacteriology, Leprosy Research Center, National
Institute of Infectious Diseases, Tokyo, Japan.
Abstract
Mycobacterium lepromatosis, an independent species from Mycobacterium
leprae, has been found to be a causative agent for diffuse lepromatous
leprosy (DLL) in Mexico, but remains poorly studied. Here, the drug
resistance-determining regions (DRDR) of folP1, rpoB and gyrA (conferring
resistance to dapsone, rifampicin and quinolone, respectively) in M.
lepromatosis from leprosy patients in Mexico were characterized. No
mutations or silent mutations were found at previously characterized major
sites in DRDR of M. lepromatosis. However, a non-synonymous mutation was
found in codon 54 between two major sites of the folP1 DRDR in M.
lepromatosis sequences. All M. lepromatosis isolates showed CAG sequence
in codon 54 of folP1. Because the next codons 53 and 55 are known as major
mutation sites for drug resistance, more detailed analysis using more
samples is needed to determine whether it influences susceptibility to
dapsone and/or efficiency of folate biosynthesis in M. lepromatosis or
not.
========================================================
94.) Red squirrels in the British Isles are infected with leprosy
bacilli.
=======================================================
Science. 2016 Nov 11;354(6313):744-747.
Avanzi C1, Del-Pozo J2, Benjak A1, Stevenson K3, Simpson VR4, Busso P1,
McLuckie J3, Loiseau C1, Lawton C5, Schoening J6, Shaw DJ2, Piton J1,
Vera-Cabrera L7, Velarde-Felix JS7, McDermott F6, Gordon SV6,8,9,10, Cole
ST11, Meredith AL12.
Author information
Abstract
Leprosy, caused by infection with Mycobacterium leprae or the recently
discovered Mycobacterium lepromatosis, was once endemic in humans in the
British Isles. Red squirrels in Great Britain (Sciurus vulgaris) have
increasingly been observed with leprosy-like lesions on the head and
limbs. Using genomics, histopathology, and serology, we found M.
lepromatosis in squirrels from England, Ireland, and Scotland, and M.
leprae in squirrels from Brownsea Island, England. Infection was detected
in overtly diseased and seemingly healthy animals. Phylogenetic
comparisons of British and Irish M. lepromatosis with two Mexican strains
from humans show that they diverged from a common ancestor around 27,000
years ago, whereas the M. leprae strain is closest to one that circulated
in Medieval England. Red squirrels are thus a reservoir for leprosy in the
British Isles.
========================================================
95.) Unsolved matters in leprosy: a descriptive review and call for
further research.
=========================================================
Ann Clin Microbiol Antimicrob. 2016 May 21;15(1):33. doi:
10.1186/s12941-016-0149-x.
Franco-Paredes C1,2, Rodriguez-Morales AJ3.
Author information
1Infectious Diseases Clinic, Phoebe Putney Memorial Hospital, 507 3rd
Avenue, Albany, GA, 31721, USA. carlos.franco.paredes@gmail.com.
2Hospital Infantil de México, Federico Gómez, Mexico D.F., Mexico.
carlos.franco.paredes@gmail.com.
3Public Health and Infection Research Group, Faculty of Health Sciences,
Universidad Tecnológica de Pereira, Pereira, Risaralda, Colombia.
Abstract
Leprosy, a chronic mycobacterial infection caused by Mycobacterium leprae,
is an infectious disease that has ravaged human societies throughout
millennia. This ancestral pathogen causes disfiguring cutaneous lesions,
peripheral nerve injury, ostearticular deformity, limb loss and
dysfunction, blindness and stigma. Despite ongoing efforts in interrupting
leprosy transmission, large numbers of new cases are persistently
identified in many endemic areas. Moreover, at the time of diagnosis, most
newly identified cases have considerable neurologic disability. Many
challenges remain in our understanding of the epidemiology of leprosy
including: (a) the precise mode and route of transmission; (b) the
socioeconomic, environmental, and behavioral factors that promote its
transmission; and
(c) strategies to achieve early diagnosis and prevent neurologic
impairment to reduce the large burden of disability among newly identified
cases; and among those who endure long-term disability in spite of
completing multidrug therapy.
========================================================
96.) Delayed Diagnosis, Leprosy Reactions, and Nerve Injury Among
Individuals With Hansen's Disease Seen at a United States Clinic.
==========================================================
Open Forum Infect Dis. 2016 Mar 25;3(2):ofw063. doi: 10.1093/ofid/ofw063.
eCollection 2016.
Leon KE1, Jacob JT2, Franco-Paredes C3, Kozarsky PE2, Wu HM2, Fairley
JK2.
Author information
1Emory University.
2Division of Infectious Diseases, Department of Medicine , Emory
University School of Medicine.
3Phoebe Putney Memorial Hospital, Albany, Georgia; Hospital Infantil de
Mexico, Federico Gomez.
Abstract
Background. Hansen's disease (HD), or leprosy, is uncommon in the United
States. We sought to describe the characteristics of patients with HD in a
US clinic, including an assessment of delays in diagnosis and HD
reactions, which have both been associated with nerve damage. Methods. A
retrospective chart review was conducted on patients seen at an HD clinic
in the southern United States between January 1, 2002 and January 31,
2014. Demographic and clinical characteristics were summarized, including
delays in diagnosis, frequency of reactions, and other complications
including peripheral neuropathy. Results. Thirty patients were seen during
the study time period. The majority of patients were male (73%) and had
multibacillary disease (70%). Brazil, Mexico, and the United States were
the most frequent of the 14 countries of origin. Hansen's disease
"reactions", severe inflammatory complications, were identified among 75%
of patients, and nerve damage was present at diagnosis in 36% of patients.
The median length of time between symptom onset and diagnosis was long at
12 months (range, 1-96), but no single factor was associated with a delay
in diagnosis. Conclusions. The diagnosis of HD was frequently delayed
among patients referred to our US clinic. The high frequency of reactions
and neuropathy at diagnosis suggests that further efforts at timely
diagnosis and management of this often unrecognized disease is needed to
prevent the long-term sequelae associated with irreversible nerve damage.
========================================================
97.) The leprosy agents Mycobacterium lepromatosis and Mycobacterium
leprae in Mexico.
==========================================================
Han XY1, Sizer KC, Velarde-Félix JS, Frias-Castro LO, Vargas-Ocampo F.
Author information
1Clinical Microbiology Laboratory, University of Texas MD Anderson Cancer
Center, Houston, TX 77030, USA.
Abstract
BACKGROUND:
Mycobacterium leprae was the only known cause of leprosy until 2008, when
a new species, named Mycobacterium lepromatosis, was found to cause
diffuse lepromatous leprosy (DLL), a unique form of leprosy endemic in
Mexico.
METHODS:
We sought to differentiate the leprosy agents among 120 Mexican patients
with various clinical forms of leprosy and to compare their relative
prevalences and disease features. Archived skin biopsy specimens from
these patients were tested for both M. leprae and M. lepromatosis using
polymerase chain reaction-based species-specific assays.
RESULTS:
Etiologic species were confirmed in 87 (72.5%) patients, of whom 55 were
infected with M. lepromatosis, 18 with M. leprae, and 14 with both
organisms. The endemic regions of each agent differed but overlapped.
Patients with M. lepromatosis were younger and were distributed across
more states; their clinical diagnoses included DLL (n = 13), lepromatous
leprosy (LL) (n = 34), and eight other forms of leprosy. By contrast, the
diagnoses of patients with M. leprae did not include DLL but did include
LL (n = 15) and three other forms of leprosy. Thus, M. lepromatosis caused
DLL specifically (P = 0.023). Patients with M. lepromatosis also showed
more variable skin lesions; the extremities were the most common sites of
biopsy in these patients. Finally, patients with dual infections
manifested all clinical forms and accounted for 16.1% of all
species-confirmed cases.
CONCLUSIONS:
Mycobacterium lepromatosis is another cause of leprosy and is probably
more prevalent than M. leprae in Mexico. It mainly causes LL and also
specifically DLL. Dual infections caused by both species may occur in
endemic areas.
========================================
98.) Identification of the leprosy agent Mycobacterium lepromatosis in
Singapore.
========================================
J Drugs Dermatol. 2012 Feb;11(2):168-72.
Han XY1, Sizer KC, Tan HH.
Author information
1Clinical Microbiology Laboratory, The University of Texas M.D. Anderson
Cancer Center, Houston, TX, USA. xhan@mdanderson.org
Abstract
BACKGROUND:
A new leprosy-causing species, namely Mycobacterium lepromatosis, was
discovered recently to be the cause of diffuse lepromatous leprosy (DLL)
in Mexico. It is unknown whether this organism exists beyond Mexico.
METHODS:
We sought to determine the identity of the mycobacteria in the skin tissue
of two patients from Singapore who died of DLL. DNA was extracted from
archived biopsy tissue, and conserved polymerase chain reaction primers
were used to amplify and sequence two to three mycobacterial genes in each
skin sample.
RESULTS:
Both M. lepromatosis and the well-known leprosy agent Mycobacterium leprae
were identified in each DLL skin sample. The M. lepromatosis gene
sequences from the Singapore cases matched 99.9% with the known Mexican M.
lepromatosis strain, but they only matched the corresponding M. leprae
sequences by 89.2%.
CONCLUSIONS:
The new species M. lepromatosis exists beyond Mexico and is the cause of
DLL in Singapore. It may cause dual infections along with M. leprae in
endemic areas. Archived skin biopsy can be used to differentiate the
leprosy agents.
=======================================================
99.) A new Mycobacterium species causing diffuse lepromatous leprosy.
========================================================
Am J Clin Pathol. 2008 Dec;130(6):856-64. doi: 10.1309/AJCPP72FJZZRRVMM.
Han XY1, Seo YH, Sizer KC, Schoberle T, May GS, Spencer JS, Li W, Nair
RG.
Author information
1Department of Laboratory Medicine, The University of Texas MD Anderson
Cancer Center, Houston, TX 77030, USA.
Abstract
Mycobacterium leprae causes leprosy. M leprae strains collected worldwide
have been genetically clonal, which poorly explains the varying severity
and clinical features of the disease. We discovered a new Mycobacterium
species from 2 patients who died of diffuse lepromatous leprosy (DLL). The
Mycobacterium was purified from heavily infected, freshly frozen autopsy
liver tissue followed by DNA extraction in 1 case. Paraffin-embedded skin
tissue was used for DNA extraction in another case. Six genes of the
organism were amplified by polymerase chain reaction, sequenced on cloning
or from amplicons, and analyzed. Significant genetic differences with M
leprae were found, including a 2.1% divergence of the 16S ribosomal RNA
(rRNA) gene, a highly conserved marker of bacterial evolution, and 6% to
14% mismatches among 5 less conserved genes. Phylogenetic analyses of the
genes of 16S rRNA, rpoB, and hsp65 indicated that the 2 most related
organisms evolved from a common ancestor that had branched from other
mycobacteria. These results and the unique clinicopathologic features of
DLL led us to propose Mycobacterium lepromatosis sp nov. This species may
account for some of the clinical and geographic variability of leprosy.
This finding may have implications for the research and diagnosis of
leprosy.
========================================================
100.) Zoonotic Leprosy in the Southeastern United States.
=======================================================
Emerg Infect Dis. 2015 Dec;21(12):2127-34. doi: 10.3201/eid2112.150501.
Sharma R, Singh P, Loughry WJ, Lockhart JM, Inman WB, Duthie MS, Pena MT,
Marcos LA, Scollard DM, Cole ST, Truman RW.
Abstract
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.
========================================================
101.) Borderline tuberculoid leprosy in a woman from the state of Georgia
with armadillo exposure.
=========================================================
J Am Acad Dermatol. 2006 Oct;55(4):714-6.
Lane JE1, Walsh DS, Meyers WM, Klassen-Fischer MK, Kent DE, Cohen DJ.
Author information
1Division of Dermatology, Department of Internal Medicine, Mercer
University School of Medicine, Macon, Georgia 31217, USA.
joshua.lane@lycos.com
Abstract
In the southern and southeastern United States, the 9-banded armadillo is
an important reservoir for Mycobacterium leprae, the causative agent of
leprosy (Hansen's disease). Here, we describe a woman living in Georgia
with borderline tuberculoid leprosy who worked for many years in a garden
where armadillos burrowed or were buried. There was no history of foreign
travel or known exposure to a person with leprosy. Treatment with 6
once-monthly combined doses of rifampin, ofloxacin, and minocycline was
successful.
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102.) Minocycline in leprosy patients with recent onset clinical nerve
function impairment.
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Dermatol Ther. 2017 Jan;30(1). doi: 10.1111/dth.12404. Epub 2016 Aug 23.
Narang T1, Arshdeep1, Dogra S1.
Author information
1Department of Dermatology, Venereology and Leprology, Postgraduate
Institute of Medical Education and Research (PGIMER), Chandigarh, 160012,
India.
Abstract
Nerve function impairment (NFI) in leprosy may occur and progress despite
multidrug therapy alone or in combination with corticosteroids. We
observed improvement in neuritis when minocycline was administered in
patients with type 2 lepra reaction. This prompted us to investigate the
role of minocycline in recent onset NFI, especially in corticosteroid
unresponsive leprosy patients. Leprosy patients with recent onset clinical
NFI (<6 months), as determined by Monofilament Test (MFT) and Voluntary
Muscle Test (VMT), were recruited. Minocycline 100mg/day was given for 3
months to these patients. The primary outcome was the proportion of
patients with 'restored,' 'improved,' 'stabilized,' or 'deteriorated' NFI.
Secondary outcomes included any improvement in nerve tenderness and pain.
In this pilot study, 11 patients were recruited. The progression of NFI
was halted in all; with 9 out of 11 patients (81.82%) showing ?restored?
or ?improved? sensory or motor nerve functions, on assessment with MFT and
VMT. No serious adverse effects due to minocycline were observed. Our
pilot study demonstrates the efficacy and safety of minocycline in recent
onset NFI in leprosy patients. However, larger and long term comparative
trials are needed to validate the efficacy of minocycline in leprosy
neuropathy.
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103.) Leprosy Drug Resistance Surveillance in Colombia: The Experience of
a Sentinel Country.
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PLoS Negl Trop Dis. 2016 Oct 5;10(10):e0005041. doi:
10.1371/journal.pntd.0005041. eCollection 2016.
Beltrán-Alzate C1, López Díaz F2, Romero-Montoya M1, Sakamuri R3, Li W3,
Kimura M3, Brennan P3, Cardona-Castro N1,4.
Author information
1Instituto Colombiano de Medicina Tropical-Universidad CES Sabaneta,
Antioquia, Colombia.
2Sanatorio de Agua de Dios, Agua de Dios Cundinamarca, Colombia.
3Department of Microbiology, Immunology and Pathology, Colorado State
University, Fort Collins, Colorado, United States of America.
4Facultad de Medicina. Universidad CES, Medellín, Colombia.
Abstract
An active search for Mycobacterium leprae drug resistance was carried out,
243 multibacillary patients from endemic regions of Colombia were included
from 2004 to 2013 in a surveillance program. This program was a World
Health Organization initiative for drug resistance surveillance in
leprosy, where Colombia is a sentinel country. M. leprae DNA from slit
skin smear and/or skin biopsy samples was amplified and sequenced to
identify mutations in the drug resistance determining region (DRDR) in
rpoB, folP1, gyrA, and gyrB, the genes responsible for rifampicin, dapsone
and ofloxacin drug-resistance, respectively. Three isolates exhibited
mutations in the DRDR rpoB gene (Asp441Tyr, Ser456Leu, Ser458Met), two in
the DRDR folP1 gene (Thr53Ala, Pro55Leu), and one isolate exhibited
mutations in both DRDR rpoB (Ser456Met) and DRDR folP1 (Pro55Leu),
suggesting multidrug resistance. One isolate had a double mutation in
folP1 (Thr53Ala and Thr88Pro). Also, we detected mutations outside of DRDR
that required in vivo evaluation of their association or not with drug
resistance: rpoB Arg505Trp, folP1 Asp91His, Arg94Trp, and Thr88Pro, and
gyrA Ala107Leu. Seventy percent of M. leprae mutations were related to
drug resistance and were isolated from relapsed patients; the likelihood
of relapse was significantly associated with the presence of confirmed
resistance mutations (OR range 20.1-88.7, p < 0.05). Five of these
relapsed patients received dapsone monotherapy as a primary treatment. In
summary, the current study calls attention to M. leprae resistance in
Colombia, especially the significant association between confirmed
resistance mutations and relapse in leprosy patients. A high frequency of
DRDR mutations for rifampicin was seen in a region where dapsone
monotherapy was used extensively.
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104.) Drug resistance in Mycobacterium leprae from patients with leprosy
in China.
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Clin Exp Dermatol. 2015 Dec;40(8):908-11. doi: 10.1111/ced.12665. Epub
2015 May 19.
Liu D1,2,3, Zhang Q4, Sun Y1,2, Wang C1,2, Zhang Y1,2,3, Fu X1,2, Chen
M1,2, Zhou G1, Yu X1, Wang J1, Liu H1,2,5,6, Zhang F1,2,5,6.
Author information
Abstract
BACKGROUND:
Previous studies of drug resistance have shown that mutations in the drug
resistance-determining region (DRDR) in the Folp1, RpoB and GyrA genes of
Mycobacterium leprae are responsible for resistance to dapsone, rifampin
and ofloxacin, respectively.
AIM:
To investigate the prevalence of mutations in genes associated with drug
resistance in M. leprae isolates from patients with leprosy in Shandong
Province.
METHODS:
The DRDR in the FolP1, RpoB and GyrA genes was analysed by direct
sequencing of the PCR product from 85 isolates of M. leprae sampled from
patients with leprosy in Shandong, China.
RESULTS:
Sequencing results were obtained for FolP1, RpoB and GyrA in 67, 57 and 81
of the 85 samples, with mutation rates of 1.5% (1/67), 8.8% 5/57 and 25.9%
(21/81). Three multidrug-resistant samples were found among the new cases:
one had a mutation in both Folp1 and RpoB, while the other two had a
mutation in both RpoB and GyrA.
CONCLUSIONS:
Primary resistance appears to be to either single drugs or combinations of
two drugs. The resistance rate to dapsone seems to be low. To our
knowledge, this is the first case of multidrug-resistant M. leprae from
China.
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105.) [Study of rifampin and dapsone resistance in three patients with
recurring leprosy].
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Rev Panam Salud Publica. 2008 Feb;23(2):73-7.
[Article in Spanish]
Hernández E1, Cardona-Castro N, Rodríguez G, Villegas S, Beltrán C, Kimura
M, Vissa VD, Gómez Y.
Author information
Abstract
OBJECTIVE:
To detect the presence of rifampin- and dapsone-resistant strains of
Mycobacterium leprae in three patients with recurring leprosy and
clinically-suspected antimicrobial resistance through molecular
techniques.
METHODS:
A retrospective, descriptive study was conducted of three multibacillary
patients at the "Agua de Dios" Sanitarium in Cundinamarca, Colombia, that
presented leprosy relapses that were documented by medical history,
bacilloscopy, and biopsy. Biopsies were taken of the skin lesions and the
bacteria were subject to DNA extraction and purification. Regions of the
rpoB and folP1 genes associated with antimicrobial resistance were
amplified and subjected to touch-down polymerase chain reaction and the
amplified products were sequenced using the Sanger method.
RESULTS:
A punctual mutation was identified in nucleotide 1367 of the rpoB gene in
two of the samples studied. This mutation was not found in the folP1 gene
of any of the three patients.
CONCLUSIONS:
The mutation identified showed strains of rifampin-resistant M. leprae in
two of the three patients with recurring leprosy. Mutations that indicate
dapsone-resistance were not detected in any of the three patients.
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106.) Possible mode of emergence for drug-resistant leprosy is revealed by
an analysis of samples from Mexico.
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Jpn J Infect Dis. 2010 Nov;63(6):412-6.
Matsuoka M1, Suzuki Y, Garcia IE, Fafutis-Morris M, Vargas-González A,
Carreño-Martinez C, Fukushima Y, Nakajima C.
Author information
1Leprosy Research Center, National Institute of Infectious Diseases, Tokyo
189-0002, Japan. matsuoka@nih.gp.jp
Abstract
Mexico is a country with sporadic leprosy cases, and the reemergence of
drug resistance is a concern. In this study, molecular analysis of
Mycobacterium leprae was employed to clarify the spread of drug-resistant
leprosy. Thus, drug resistance-determining regions in the folP1, rpoB, and
gyrA genes, which are associated with resistance to dapsone, rifampicin,
and ofloxacin, respectively, were analyzed by direct sequencing of the PCR
product. No mutations in the folP1 gene were observed in any of the 72
slit skin samples obtained from 38 patients, although two samples carrying
a mutation at codon 425 in the rpoB gene, which confers resistance to
rifampicin, a key component of multidrug therapy, were identified. In
addition, a mutation at codon 91 in the gyrA gene, which correlates with
ofloxacin resistance, was found in one sample. These results demonstrate
the existence of rifampicin- and ofloxacin-resistant leprosy.
Interestingly, wild-type and mutant sequences in the gyrA gene were found
to coexist in one clinical sample. In addition, all three drug
resistance-related mutations were found in only one of the two earlobes of
the patients concerned, suggesting a possible pathway for the spread of
drug-resistant M. leprae.
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107.) What is the evidence that the putative Mycobacterium lepromatosis
species causes diffuse lepromatous leprosy?
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Gillis TP, Scollard DM, Lockwood DN.
Abstract
Han et al. have made a retrospective isolation of DNA from two patients
with fatal Lucio's phenomenon. This DNA does have some molecular
differences to M. leprae and may constitute a variant of M. leprae.
However the experiments and data needed to confirm that this is a new
leprosy-causing species have not yet been done. We have outlined the work
that does need to be done. For the moment the assertion that 'M.
lepromatosis' is a new leprosy-causing species is not proven.
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108.) Treatment of severe refractory erythema nodosum leprosum with tumor
necrosis factor inhibitor Etanercept.
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Chowdhry S1, Shukla A2, D'souza P1, Dhali T1, Jaiswal P1.
Author information
1Department of Dermatology, Venereology, and Leprology, ESI-Postgraduate
Institute of Medical Sciences and Research, New Delhi, India.
2Department of Dermatology, Venereology, and Leprology, ESI-Postgraduate
Institute of Medical Sciences and Research, New Delhi, India. Electronic
address: drakhilesh89@gmail.com.
Abstract
Erythema nodosum leprosum (ENL) is a common complication of lepromatous
leprosy. Some patients unresponsive to conventional, first-line
therapeutics develop recurrent, recalcitrant ENL. Here, we report a case
of severe refractory ENL that was successfully treated with Etanercept.
Biologics may be considered as therapeutic alternatives in management of
severe, recalcitrant ENL.
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