LA LEPRA, 2.000 AÑOS DESPUES./ THE LEPROSY, 2000 YEARS LATER

La Lepra, 2.000 años despues. !

  

  The Leprosy, 2.000 years later. ! 

 

LEPRA EN DEDO PULGAR DE MANO DERECHA CON INCAPACIDAD FUNCIONAL

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PUBLICADA 2017 ACTUALIZADA 2023

EDITORIAL ESPAÑOL
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Hola amigos de la red, DERMAGIC hoy con el tema de la ENFERMEDAD DE HANSEN (LEPRA)2.000 AÑOS DESPUES. 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 LEVITICO.  

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 cientificos 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 Frances 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 denomino MYCOBATERIUM LEPROMATOSIS, hallazgo hecho en MEXICO, ESTADOS UNIDOS y posteriormente SINGAPUR, INDIA y encontrado también en las ardillas rojas de las ISLAS BRITANICAS, las cuales hoy dia son un reservorio para la lepra en estas islas.


2.) La aparición de resistencia a la MTD (Multi Drug Therapy) tratamiento CLASICO 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, ACIDO 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 antimicobacteriana 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  NORTEMERICA desde 1.998. También La utilización de Antileucotrienos como el ZAFIRLUKAST para tratar la Reacción leprosa, y otras nuevas como el ETANERCEPT (Inhibidor del factor de necrosis tumoral).



5.) La aparición de la inmunoquimioterapia como alternativa de tratamiento tales como: inmunoquimioterapia con interferon-gamma y terapia multiple (MTD), ANTIBIOTICOS y terapia multiple, vacunas y MTD.


6.) Existen 2 vacunas inmunoterapeuticas para la lepra: 

A.) Una de ellas basadas en el Micobacterium 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.

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 diagnosticas (PCR) para observar el comportamiento y pronostico 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 LEPROMATOSUS.

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 protectivo de 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 parasito 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). 

16. De acuerdo con estudios, la vacuna contra la lepra aún está en su fase experimental,

así como otros tratamientos que podrían inducir reactividad inmunológica celular contra esta enfermedad.

17.) Actualmente se le han dado dos usos racionales a las vacunas experimentales contra la lepra: uno es la inmunoterapia con el propósito de que en los pacientes inmunológicamente anérgicos logren despertar una respuesta inmunológica celular y así eliminen su infección.

18,) El otro empleo es en la inmunoprofilaxis, a fin de proteger a una población en riesgo de adquirir la infección o la enfermedad. Hasta ahora no se ha obtenido ninguna vacuna contra la lepra, hay varios candidatos en el desarrollo, pero solo son dosis experimentales.

CONCLUSIÓN:

Hoy DÍA, 2.023 la lepra sigue existiendo en el mundo !!!!

SIGAMOS LUCHANDO CONTRA ELLA !!!  

Saludos a todos !!!

 
Dr. José Lapenta.

Dr. Jose M. Lapenta

EDITORIAL ENGLISH

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Hello friends of the network, DERMAGIC today with the theme of DISEASE HANSEN (LEPRA) 2,000 YEARS LATER. This disease really has more than 2.000 Years of evolution on our planet, since the first descriptions of the Disease dating from the sixteenth century BC, with the first references In the sacred book of ancient India. In the Bible appears in the LEVITICUS.

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 MYCOBATERIUM 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

Diaminodiphenylsulfone (DDS), Clofazimine and rifampicin, also resistance to treatment with MINOCYCLINE and OFLOXACIN.) With the new SCHEMES ordered by the World Health Organization (WHO).

3.) The confirmation that antibiotics as OFLOXACIN, MINOCYCLINE, CLAVULANIC ACID plus AMOXACILLIN AND CLARITHROMYCIN are Highly bactericidal against Mycobacterium leprae, in fact MINOCYCCLINE 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 ETARNECEPT (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.

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 MYCOBATERIUM LEPROMATOSUS.

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).

16. According to studies, the leprosy vaccine is still in its experimental phase,

as well as other treatments that could induce cellular immune reactivity against this disease.

17.) Currently, two rational uses have been given to the experimental vaccines against leprosy: one is immunotherapy with the purpose of awakening a cellular immune response in immunologically anergic patients and thus eliminating their infection.

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.

CONCLUSION:  

TODAY, 2.023 LEPROSY STILL EXIST IN THE WORLD !!!!
LET'S KEEP FIGHTING IT !!!   

Greetings to all !!!

Dr. José Lapenta. 

Dr. Jose M Lapenta

 
=================================================================== REFERENCIAS BIBLIOGRAFICAS / BIBLIOGRAPHICAL REFERENCES
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1.) A 21-kDa surface protein of Mycobacterium leprae binds peripheral nerve
laminin-2 and mediates Schwann cell invasion.
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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Author
Shimoji Y; Ng V; Matsumura K; Fischetti VA; Rambukkana A
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.
============================================================
3.) Delayed-type hypersensitivity to Mycobacterium leprae soluble antigens
as a test for infection with the leprosy bacillus.
============================================================
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.
============================================================
4.) Detection of M. leprae by gene amplification; combined ethidium-bromide
staining and probe hybridization.
============================================================
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.
============================================================
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.
============================================================
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.
============================================================
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.
============================================================
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.
============================================================
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.
============================================================
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.
============================================================
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.
============================================================
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
============================================================
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.
============================================================
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.
============================================================
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.
============================================================
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.
============================================================
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.
============================================================
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.
============================================================
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.
============================================================
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.
============================================================
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.
============================================================
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.
============================================================
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)
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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.
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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).
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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.
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85.) [A socioeconomic characterization of leprosy patients at the dermatology clinic in Maracaibo, VENEZUELA: a case study]
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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.
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86.) [The current challenge of imported leprosy in Spain: a study of 7 cases].
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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.
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87.) Leprosy trends at a tertiary care hospital in Mumbai, India, from 2008 to 2015.
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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.
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88.) Childhood leprosy: a retrospective descriptive study from Government Medical College, Kozhikode, Kerala, India.
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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.
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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.
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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.
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90.) Minocycline successfully treats exaggerated granulomatous hypersensitivity reaction to Mw immunotherapy.
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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.
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91.) Generalized granulomatous dermatitis following Mycobacterium w (Mw) immunotherapy in lepromatous leprosy.
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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.
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92.) World Leprosy Day
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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.
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93.) Mutations in the drug resistance-determining region of Mycobacterium lepromatosis isolated from leprosy patients in Mexico.
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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.
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94.) Red squirrels in the British Isles are infected with leprosy bacilli.
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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.
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95.) Unsolved matters in leprosy: a descriptive review and call for further research.
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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.
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96.) Delayed Diagnosis, Leprosy Reactions, and Nerve Injury Among Individuals With Hansen's Disease Seen at a United States Clinic.
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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.
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97.) The leprosy agents Mycobacterium lepromatosis and Mycobacterium leprae in Mexico.
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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.
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98.) Identification of the leprosy agent Mycobacterium lepromatosis in Singapore.
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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.
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99.) A new Mycobacterium species causing diffuse lepromatous leprosy.
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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.
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100.) Zoonotic Leprosy in the Southeastern United States.
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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.
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101.) Borderline tuberculoid leprosy in a woman from the state of Georgia with armadillo exposure.
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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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