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1.
Scand J Immunol ; 93(5): e13010, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33325540

RESUMO

World Health Organisation recommends the practice of BCG vaccination at birth in countries which have a high incidence of tuberculosis and/or high leprosy burden. The BCG vaccination is considered safe for a competent immune system. However, in children with weakened immune systems cause of which can be primary or secondary, the vaccine may lead to side effects which can be localized or disseminated. In this study, we report a spectrum of inborn errors of immunity (IEI) commonly referred to as primary immunodeficiency disorders (PIDs) diagnosed in a large cohort of patients presenting with complications to BCG vaccination from India. Retrospective data analysis of patients referred to ICMR- National Institute of Immunohematology (ICMR-NIIH) for IEI workup between 2007 and 2019 was done. IEI was identified in n = 52/90 (57.7%) patients presenting with BCG complications. Of these, n = 13(14.4%) patients were diagnosed with severe combined immune deficiency, n = 15(16.7%) with chronic granulomatous disease, n = 19(21.1%) with Inborn errors of IFN-γ immunity, n = 4(4.4%) with Combined immunodeficiency and n = 1(1.1%) with Leucocyte Adhesion Deficiency type1. Majority of cases with BCGosis (88%) had an underlying IEI. This study strongly highlights the need for evaluation of patients with BCG complications for underlying IEI. While disseminated BCGosis strongly predicts underlying IEI, even localized persistent adenitis may be a warning sign of underlying IEI. It is also strongly recommended to record a family history of previous sibling death prior to administration of this live vaccine and deferring live vaccine till the diagnosis of IEI is ruled out in cases with a positive family history.


Assuntos
Vacina BCG/efeitos adversos , Doença Granulomatosa Crônica/patologia , Imunodeficiência Combinada Severa/patologia , Tuberculose Pulmonar/prevenção & controle , Vacinação/efeitos adversos , Vacina BCG/imunologia , Feminino , Doença Granulomatosa Crônica/diagnóstico , Doença Granulomatosa Crônica/imunologia , Humanos , Índia , Lactente , Masculino , Mycobacterium tuberculosis/imunologia , Imunodeficiência Combinada Severa/diagnóstico , Imunodeficiência Combinada Severa/imunologia , Resultado do Tratamento
2.
Paediatr Respir Rev ; 36: 57-64, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32958428

RESUMO

The Bacille Calmette Guérin (BCG) vaccine was developed over a century ago and has become one of the most used vaccines without undergoing a modern vaccine development life cycle. Despite this, the vaccine has protected many millions from severe and disseminated forms of tuberculosis (TB). In addition, BCG has cross-mycobacterial effects against non-tuberculous mycobacteria and off-target (also called non-specific or heterologous) effects against other infections and diseases. More recently, BCG's effects on innate immunity suggest it might improve the immune response against viral respiratory infections including SARS-CoV-2. New TB vaccines, developed over the last 30 years, show promise, particularly in prevention of progression to disease from TB infection in young adults. The role of BCG in the context of new TB vaccines remains uncertain as most participants included in trials have been previously BCG immunised. BCG replacement vaccines are in efficacy trials and these may also have off-target effects.


Assuntos
Adjuvantes Imunológicos/uso terapêutico , Vacina BCG/uso terapêutico , Proteção Cruzada/imunologia , Imunidade Heteróloga/imunologia , Infecções por Mycobacterium não Tuberculosas/prevenção & controle , Vacinas contra a Tuberculose/uso terapêutico , Tuberculose/prevenção & controle , Vacina BCG/imunologia , Úlcera de Buruli/microbiologia , Úlcera de Buruli/prevenção & controle , COVID-19/prevenção & controle , Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 1/imunologia , Humanos , Hipersensibilidade/epidemiologia , Hipersensibilidade/imunologia , Lactente , Mortalidade Infantil , Hanseníase/microbiologia , Hanseníase/prevenção & controle , Infecções por Mycobacterium não Tuberculosas/microbiologia , Micobactérias não Tuberculosas/imunologia , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/imunologia , Vacinas contra a Tuberculose/imunologia
3.
Pharmazie ; 75(8): 375-380, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32758336

RESUMO

Diabetes mellitus (DM) is one of the major risk factors for COVID-19 complications as it is one of the chronic immune-compromising conditions especially if patients have uncontrolled diabetes, poor HbA1c and/or irregular blood glucose levels. Diabetic patients' mortality rates with COVID-19 are higher than those of cardiovascular or cancer patients. Recently, Bacillus Calmette-Guérin (BCG) vaccine has shown successful results in reversing diabetes in both rats and clinical trials based on different mechanisms from aerobic glycolysis to beta cells regeneration. BCG is a multi-face vaccine that has been used extensively in protection from tuberculosis (TB) and leprosy and has been repositioned for treatment of bladder cancer, diabetes and multiple sclerosis. Recently, COVID-19 epidemiological studies confirmed that universal BCG vaccination reduced morbidity and mortality in certain geographical areas. Countries without universal policies of BCG vaccination (Italy, Nederland, USA) have been more severely affected compared to countries with universal and long-standing BCG policies that have shown low numbers of reported COVID-19 cases. Some countries have started clinical trials that included a single dose BCG vaccine as prophylaxis from COVID-19 or an attempt to minimize its side effects. This proposed research aims to use BCG vaccine as a double-edged weapon countering both COVID-19 and diabetes, not only as protection but also as therapeutic vaccination. The work includes a case study of regenerated pancreatic beta cells based on improved C-peptide and PCPRI laboratory findings after BCG vaccination for a 9 year old patient. The patient was re-vaccinated based on a negative tuberculin test and no scar at the site of injection of the 1st BCG vaccination at birth. The authors suggest and invite the scientific community to take into consideration the concept of direct BCG re-vaccination (after 4 weeks) because of the reported gene expressions and exaggerated innate immunity consequently. As the diabetic MODY-5 patient (mutation of HNF1B, Val2Leu) was on low dose Riomet® while eliminating insulin gradually, a simple analytical method for metformin assay was recommended to ensure its concentration before use as it is not approved yet by the Egyptian QC labs.


Assuntos
Vacina BCG/administração & dosagem , Infecções por Coronavirus/imunologia , Diabetes Mellitus/imunologia , Células Secretoras de Insulina/citologia , Pneumonia Viral/imunologia , Animais , Vacina BCG/imunologia , COVID-19 , Criança , Infecções por Coronavirus/complicações , Diabetes Mellitus/fisiopatologia , Humanos , Masculino , Pandemias , Pneumonia Viral/complicações , Ratos , Regeneração/imunologia , Fatores de Risco , Vacinação/métodos
4.
BMC Infect Dis ; 19(1): 520, 2019 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-31196008

RESUMO

BACKGROUND: Leprosy is is still considered a public health issue and in Colombia 7-10% of new cases are found in children, indicating both active transmission and social inequality. We hypothesized that circulating antibodies against Natural Octyl Disaccharide-Leprosy IDRI Diagnostic (NDO-LID) (a combination of Mycobacterium leprae antigens) could reveal the social and environmental aspects associated with higher frequencies of M. leprae infection among children and adolescents in Colombia. METHODS: An observational cross-sectional study was conducted involving sampling from 82 children and adolescents (younger than 18 years of age) who had household contact with index leprosy patients diagnosed in the last 5 years. Data were analyzed through bivariate analysis made by applying a Pearson x2 test for qualitative variables, while quantitative variables, depending on their distribution, were analyzed using either a Student's t-test or Mann-Whitney U test. Multivariate analysis was performed using a multiple regression and binomial logistic approach. RESULTS: A bivariate analysis demonstrated that antibody titers against NDO-LID were significantly greater in children and adolescents with a low socioeconomic status that had: lived in vulnerable areas of the UAChR shared region; eaten armadillo meat; exposure of over 10 years to an index case and; not received BCG immunization. Moreover, a multivariate analysis showed that residing in the UAChR region has a strong association with a greater possibility of M. leprae infection. CONCLUSIONS: M. leprae transmission persists among young Colombians, and this is associated with social and environmental conditions. An intensification of efforts to identify new leprosy cases in vulnerable and forgotten populations where M. leprae transmission continues therefore appears necessary.


Assuntos
Hanseníase/diagnóstico , Mycobacterium leprae/isolamento & purificação , Adolescente , Animais , Anticorpos Antibacterianos/sangue , Tatus , Vacina BCG/imunologia , Criança , Pré-Escolar , Colômbia/epidemiologia , Estudos Transversais , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Lactente , Hanseníase/epidemiologia , Hanseníase/transmissão , Modelos Logísticos , Masculino , Carne/análise , Carne/microbiologia , Mycobacterium leprae/imunologia , Classe Social , Estatísticas não Paramétricas
5.
Microbiol Spectr ; 7(3)2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31172908

RESUMO

Mycobacterium tuberculosis is an ancient master of the art of causing human disease. One important weapon within its fully loaded arsenal is the type VII secretion system. M. tuberculosis has five of them: ESAT-6 secretion systems (ESX) 1 to 5. ESX-1 has long been recognized as a major cause of attenuation of the FDA-licensed vaccine Mycobacterium bovis BCG, but its importance in disease progression and transmission has recently been elucidated in more detail. This review summarizes the recent advances in (i) the understanding of the ESX-1 structure and components, (ii) our knowledge of ESX-1's role in hijacking macrophage function to set a path for infection and dissemination, and (iii) the development of interventions that utilize ESX-1 for diagnosis, drug interventions, host-directed therapies, and vaccines.


Assuntos
Antígenos de Bactérias/imunologia , Proteínas de Bactérias/imunologia , Mycobacterium tuberculosis/imunologia , Mycobacterium tuberculosis/metabolismo , Tuberculose/imunologia , Sistemas de Secreção Tipo VII/imunologia , Sistemas de Secreção Tipo VII/metabolismo , Vacina BCG/imunologia , Sistemas de Secreção Bacterianos/metabolismo , Quimiocinas , Interações Hospedeiro-Patógeno , Humanos , Macrófagos/imunologia , Mycobacterium tuberculosis/patogenicidade , Necrose , Fagossomos , Tuberculose/diagnóstico , Tuberculose/tratamento farmacológico , Tuberculose/prevenção & controle , Vacinas , Virulência
7.
Artigo em Inglês | MEDLINE | ID: mdl-27458573

RESUMO

Toll-like receptor (TLR)-1 and TLR2 have been shown to be receptors for Mycobacterium leprae (M. leprae), yet it is unclear whether M. leprae can signal through alternative TLRs. Other mycobacterial species possess ligands for TLR4 and genetic association studies in human populations suggest that people with TLR4 polymorphisms may be protected against leprosy. Using human embryonic kidney (HEK)-293 cells co-transfected with TLR4, we demonstrate that M. leprae activates TLR4. We used human macrophages to show that M. leprae stimulation of cytokine production is diminished if pre-treated with TLR4 neutralizing antibody. TLR4 protein expression was up-regulated on macrophages derived from non-bacillus Calmette-Guerin (BCG) vaccinated healthy volunteers after incubation with M. leprae, whereas it was down-regulated in macrophages derived from BCG-vaccinated donors. Finally, pre-treatment of macrophages derived from BCG-naive donors with BCG reversed the effect of M. leprae on TLR4 expression. This may be a newly described phenomenon by which BCG vaccination stimulates "non-specific" protection to the human immune system.


Assuntos
Vacina BCG/imunologia , Macrófagos/metabolismo , Mycobacterium leprae/metabolismo , Receptor 4 Toll-Like/metabolismo , Animais , Anticorpos Monoclonais , Anticorpos Neutralizantes , Vacina BCG/farmacologia , Diferenciação Celular/imunologia , Citocinas/metabolismo , Células HEK293 , Humanos , Hanseníase/imunologia , Hanseníase/microbiologia , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Camundongos , Monócitos/efeitos dos fármacos , Monócitos/imunologia , Mycobacterium leprae/imunologia , Transdução de Sinais , Receptor 4 Toll-Like/biossíntese , Receptor 4 Toll-Like/imunologia
8.
Sci Rep ; 6: 21780, 2016 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-26908331

RESUMO

Antigen presenting cells (APC) are critical components of innate immunity and consequently shape the adaptive response. Leukocyte Ig Like Receptors (LILR) are innate immune receptors predominantly expressed on myeloid cells. LILR can influence the antigen presenting phenotype of monocytic cells to determine the nature of T cell responses in infections including Mycobaterium leprae. We therefore investigated the relevance of LILR in the context of Mycobacterium tuberculosis. Real-time PCR studies indicated that the transcriptional profile of the orphan receptor LILRB5 was significantly up-regulated following exposure to mycobacteria. Furthermore, LILRA1 and LILRB5 were able to trigger signalling through direct engagement of mycobacteria using tranfectant cells incorporating a reporter system. We describe for the first time the expression of this receptor on T cells, and highlight the potential relevance to mycobacterial recognition. Furthermore, we demonstrate that crosslinking of this receptor on T cells increases proliferation of cytotoxic, but not helper, T cells.


Assuntos
Antígenos CD/metabolismo , Receptores Imunológicos/metabolismo , Antígenos CD/genética , Vacina BCG/imunologia , Proliferação de Células , Células Cultivadas , Células Dendríticas/metabolismo , Expressão Gênica , Humanos , Imunidade Inata , Mycobacterium tuberculosis/imunologia , Receptores Imunológicos/genética , Linfócitos T/metabolismo , Vacinação
9.
Rev Soc Bras Med Trop ; 48(6): 739-45, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26676499

RESUMO

INTRODUCTION: Despite multidrug therapy, leprosy remains a public health issue. The intradermal Bacillus Calmette-Guérin (BCG) vaccine, Mitsuda test (lepromin skin test), and anti-phenolic glycolipid I (PGL-I) serology are widely used in leprosy studies and have shown great epidemiological value. METHODS: This longitudinal study evaluated the relative risks and benefits of these three tools by comparing results observed in household contacts (HHCs) of leprosy patients who developed leprosy with those of HHCs who did not in a population of 2,992 individuals monitored during a 10-year period. RESULTS: Seventy-five (2.5%) new leprosy cases were diagnosed, including 28 (0.9%) co-prevalent cases. Therefore, for the risk-benefit assessment, 47 (1.6%) HHCs were considered as truly diagnosed during follow-up. The comparison between healthy and affected contacts demonstrated that not only did BCG vaccination increase protection, but boosters also increased to 95% relative risk (RR) reduction when results for having two or more scars were compared with having no scars [RR, 0.0459; 95% confidence interval (CI), 0.006-0.338]. Similarly, Mitsuda reactions >7mm in induration presented 7-fold greater protection against disease development compared to reactions of 0-3mm (RR, 0.1446; 95% CI, 0.0566-0.3696). In contrast, anti-PGL-I ELISA seropositivity indicated a 5-fold RR increase for disease outcome (RR, 5.688; 95% CI, 3.2412-9.9824). The combined effect of no BCG scars, Mitsuda reaction of <7mm, and seropositivity to anti-PGL-I increased the risk for leprosy onset 8-fold (RR, 8.109; 95% CI, 5.1167-12.8511). CONCLUSIONS: The adoption of these combined assays may impose measures for leprosy control strategies.


Assuntos
Antígenos de Bactérias/imunologia , Vacina BCG/imunologia , Busca de Comunicante/estatística & dados numéricos , Glicolipídeos/imunologia , Hanseníase/imunologia , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Lactente , Recém-Nascido , Antígeno de Mitsuda/imunologia , Hanseníase/prevenção & controle , Hanseníase/transmissão , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Medição de Risco , Adulto Jovem
10.
Rev. Soc. Bras. Med. Trop ; 48(6): 739-745, Nov.-Dec. 2015. tab, graf
Artigo em Inglês | LILACS | ID: lil-767834

RESUMO

Abstract: INTRODUCTION: Despite multidrug therapy, leprosy remains a public health issue. The intradermal Bacillus Calmette-Guérin (BCG) vaccine, Mitsuda test (lepromin skin test), and anti-phenolic glycolipid I (PGL-I) serology are widely used in leprosy studies and have shown great epidemiological value. METHODS: This longitudinal study evaluated the relative risks and benefits of these three tools by comparing results observed in household contacts (HHCs) of leprosy patients who developed leprosy with those of HHCs who did not in a population of 2,992 individuals monitored during a 10-year period. RESULTS : Seventy-five (2.5%) new leprosy cases were diagnosed, including 28 (0.9%) co-prevalent cases. Therefore, for the risk-benefit assessment, 47 (1.6%) HHCs were considered as truly diagnosed during follow-up. The comparison between healthy and affected contacts demonstrated that not only did BCG vaccination increase protection, but boosters also increased to 95% relative risk (RR) reduction when results for having two or more scars were compared with having no scars [RR, 0.0459; 95% confidence interval (CI), 0.006-0.338]. Similarly, Mitsuda reactions >7mm in induration presented 7-fold greater protection against disease development compared to reactions of 0-3mm (RR, 0.1446; 95% CI, 0.0566-0.3696). In contrast, anti-PGL-I ELISA seropositivity indicated a 5-fold RR increase for disease outcome (RR, 5.688; 95% CI, 3.2412-9.9824). The combined effect of no BCG scars, Mitsuda reaction of <7mm, and seropositivity to anti-PGL-I increased the risk for leprosy onset 8-fold (RR, 8.109; 95% CI, 5.1167-12.8511). CONCLUSIONS: The adoption of these combined assays may impose measures for leprosy control strategies.


Assuntos
Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Antígenos de Bactérias/imunologia , Vacina BCG/imunologia , Busca de Comunicante/estatística & dados numéricos , Glicolipídeos/imunologia , Hanseníase/imunologia , Ensaio de Imunoadsorção Enzimática , Estudos Longitudinais , Antígeno de Mitsuda/imunologia , Hanseníase/prevenção & controle , Hanseníase/transmissão , Medição de Risco
11.
Vaccine ; 33(13): 1562-7, 2015 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-25701674

RESUMO

BACKGROUND: Although BCG is used as a vaccine against tuberculosis, it also protects against leprosy. Previous evaluation over 18 years of an intervention of two doses BCG for 3536 household contacts of leprosy patients showed that 28 (23%) out of 122 contacts diagnosed with leprosy, developed symptoms 2-10 months after vaccination. This study describes contacts of leprosy patients in Bangladesh who developed leprosy within 12 weeks after receiving a single BCG dose. METHODS: A cluster RCT in Bangladesh aims to study the effectiveness of the BCG vaccine versus BCG in combination with single dose rifampicin (SDR) given 2 to 3 months after BCG, in the prevention of leprosy among contacts of newly diagnosed leprosy patients. During the first 1,5 years of this ongoing trial we identified contacts who developed leprosy within the first 12 weeks after receiving BCG vaccination, the timeframe before SDR is given. RESULTS: We identified 21 contacts who developed leprosy within 12 weeks after BCG vaccination among 5196 vaccinated contacts (0.40%). All 21 cases presented with paucibacillary (PB) leprosy, including children and adults. About half of these cases had previously received BCG vaccination as indicated by the presence of a BCG scar; 43% presented with signs of nerve function impairment and/or Type 1 (reversal) reaction, and 56% of the index patients had multibacillary (MB) leprosy. CONCLUSION: An unexpectedly high proportion of healthy contacts of leprosy patients presented with PB leprosy within 12 weeks after receiving BCG vaccination, possibly as a result of boosted cell-mediated immunity by homologues of Mycobacterium leprae antigens in BCG. Various immunological mechanisms could underlie this phenomenon, including an immune reconstitution inflammatory syndrome (IRIS). Further studies are required to determine whether BCG vaccination merely altered the incubation period or actually changed the course of the infection from self-limiting, subclinical infection to manifest disease.


Assuntos
Antígenos de Bactérias/imunologia , Vacina BCG/efeitos adversos , Vacina BCG/imunologia , Hanseníase Paucibacilar/etiologia , Hanseníase Paucibacilar/prevenção & controle , Mycobacterium leprae/imunologia , Rifampina/administração & dosagem , Adolescente , Adulto , Idoso , Vacina BCG/uso terapêutico , Bangladesh , Criança , Quimioterapia Combinada , Características da Família , Feminino , Humanos , Síndrome Inflamatória da Reconstituição Imune/etiologia , Imunidade Celular , Hansenostáticos/administração & dosagem , Hanseníase Paucibacilar/imunologia , Masculino , Pessoa de Meia-Idade , Vacinação , Adulto Jovem
12.
PLoS Negl Trop Dis ; 9(1): e3457, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25569674

RESUMO

BACKGROUND: The only available vaccine that could be potentially beneficial against mycobacterial diseases contains live attenuated bovine tuberculosis bacillus (Mycobacterium bovis) also called Bacillus Calmette-Guérin (BCG). Even though the BCG vaccine is still widely used, results on its effectiveness in preventing mycobacterial diseases are partially contradictory, especially regarding Buruli Ulcer Disease (BUD). The aim of this case-control study is to evaluate the possible protective effect of BCG vaccination on BUD. METHODOLOGY: The present study was performed in three different countries and sites where BUD is endemic: in the Democratic Republic of the Congo, Ghana, and Togo from 2010 through 2013. The large study population was comprised of 401 cases with laboratory confirmed BUD and 826 controls, mostly family members or neighbors. PRINCIPAL FINDINGS: After stratification by the three countries, two sexes and four age groups, no significant correlation was found between the presence of BCG scar and BUD status of individuals. Multivariate analysis has shown that the independent variables country (p = 0.31), sex (p = 0.24), age (p = 0.96), and presence of a BCG scar (p = 0.07) did not significantly influence the development of BUD category I or category II/III. Furthermore, the status of BCG vaccination was also not significantly related to duration of BUD or time to healing of lesions. CONCLUSIONS: In our study, we did not observe significant evidence of a protective effect of routine BCG vaccination on the risk of developing either BUD or severe forms of BUD. Since accurate data on BCG strains used in these three countries were not available, no final conclusion can be drawn on the effectiveness of BCG strain in protecting against BUD. As has been suggested for tuberculosis and leprosy, well-designed prospective studies on different existing BCG vaccine strains are needed also for BUD.


Assuntos
Vacina BCG/imunologia , Úlcera de Buruli/prevenção & controle , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Criança , Pré-Escolar , República Democrática do Congo/epidemiologia , Feminino , Gana/epidemiologia , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Togo/epidemiologia , Adulto Jovem
13.
Int J Exp Pathol ; 96(1): 31-41, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25529580

RESUMO

Leprosy is a disease consisting of a spectrum of clinical, bacteriological, histopathological and immunological manifestations. Tuberculoid leprosy is frequently recognized as the benign polar form of the disease, while lepromatous leprosy is regarded as the malignant form. The different forms of leprosy depend on the genetic and immunological characteristics of the patient and on the characteristics of the leprosy bacillus. The malignant manifestations of lepromatous leprosy result from the mycobacterial-specific anergy that develops in this form of the disease. Using murine leprosy as a model of anergy in this study, we first induced the development of anergy to Mycobacterium lepraemurium (MLM) in mice and then attempted to reverse it by the administration of dialysable leucocyte extracts (DLE) prepared from healthy (HLT), BCG-inoculated and MLM-inoculated mice. Mice inoculated with either MLM or BCG developed a robust cell-mediated immune response (CMI) that was temporary in the MLM-inoculated group and long-lasting in the BCG-inoculated group. DLE were prepared from the spleens of MLM- and BCG-inoculated mice at the peak of CMI. Independent MLM intradermally-inoculated groups were treated every other day with HLT-DLE, BCG-DLE or MLM-DLE, and the effect was documented for 98 days. DLE administered at a dose of 1.0 U (1 × 10(6) splenocytes) did not affect the evolution of leprosy, while DLE given at a dose of 0.1 U showed beneficial effects regardless of the DLE source. The dose but not the specificity of DLE was the determining factor for reversing anergy.


Assuntos
Extratos Celulares/administração & dosagem , Anergia Clonal , Imunoterapia/métodos , Hanseníase Tuberculoide/terapia , Mycobacterium lepraemurium/imunologia , Animais , Anticorpos Antibacterianos/sangue , Vacina BCG/imunologia , Carga Bacteriana , Extratos Celulares/imunologia , Células Cultivadas , Modelos Animais de Doenças , Feminino , Imunidade Celular , Hanseníase Tuberculoide/sangue , Hanseníase Tuberculoide/imunologia , Hanseníase Tuberculoide/microbiologia , Leucócitos/efeitos dos fármacos , Leucócitos/imunologia , Leucócitos/metabolismo , Macrófagos/imunologia , Macrófagos/metabolismo , Macrófagos/microbiologia , Camundongos , Mycobacterium lepraemurium/patogenicidade , Óxido Nítrico/metabolismo , Pele/imunologia , Pele/microbiologia , Pele/patologia , Fatores de Tempo
14.
Clin Dermatol ; 33(1): 19-25, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25432807

RESUMO

Elimination of leprosy cannot be achieved by multidrug therapy alone, and new tools are needed to prevent leprosy. A randomized controlled trial with chemoprophylaxis for contacts of leprosy patients using a single dose of rifampicin (SDR) has shown an overall protective effect of approximately 60%, effective in the first 2 years after the intervention. When a contact who previously received bacillus Calmette-Guérin (BCG) vaccination also receives SDR, the protective effect is additive, approximating 80%. Vaccine trials have been conducted with BCG, often in combination with Mycobacterium leprae or related Mycobacterium vaccines as immunoprophylaxis for contacts of leprosy patients, with BCG giving the best results. Meta-analysis shows that the protective effect of BCG vaccination is larger in observational studies than in trials, 60% versus 41%, and is higher among contacts of leprosy patients than among the general population, 68% versus 53%. We believe that a future leprosy control strategy should include contact management, consisting of a contact survey, at which time preventive interventions could be added, such as chemoprophylaxis and immunoprophylaxis. Modeling studies have shown that both interventions will lower the incidence of leprosy in the population. Implementation studies of such contact-based strategy are now called for.


Assuntos
Vacina BCG/administração & dosagem , Quimioprevenção/métodos , Controle de Doenças Transmissíveis/métodos , Imunização/métodos , Hansenostáticos/uso terapêutico , Hanseníase/prevenção & controle , Vacina BCG/imunologia , Feminino , Saúde Global , Humanos , Hanseníase/epidemiologia , Hanseníase/transmissão , Masculino , Mycobacterium leprae/isolamento & purificação , Estudos Observacionais como Assunto , Prevalência , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco , Organização Mundial da Saúde
15.
In. Virmond, Marcos da Cunha Lopes; Grzybowski, Andrzej. Clinics in Dermatology: Leprosy: 1. New York, Elsevier, 2015. p.19-25, tab.
Não convencional em Inglês | SES-SP, HANSEN, SESSP-ILSLACERVO, SES-SP | ID: biblio-1048268

RESUMO

Elimination of leprosy cannot be achieved by multidrug therapy alone, and new tools are needed to prevent leprosy. A randomized controlled trial with chemoprophylaxis for contacts of leprosy patients using a single dose of rifampicin (SDR) has shown an overall protective effect of approximately 60%, effective in the first 2 years after the intervention. When a contact who previously received bacillus Calmette-Guérin (BCG) vaccination also receives SDR, the protective effect is additive, approximating 80%. Vaccine trials have been conducted with BCG, often in combination with Mycobacterium leprae or related Mycobacterium vaccines as immunoprophylaxis for contacts of leprosy patients, with BCG giving the best results. Meta-analysis shows that the protective effect of BCG vaccination is larger in observational studies than in trials, 60% versus 41%, and is higher among contacts of leprosy patients than among the general population, 68% versus 53%. We believe that a future leprosy control strategy should include contact management, consisting of a contact survey, at which time preventive interventions could be added, such as chemoprophylaxis and immunoprophylaxis. Modeling studies have shown that both interventions will lower the incidence of leprosy in the population. Implementation studies of such contact-based strategy are now called for.


Assuntos
Vacina BCG/administração & dosagem , Imunização/métodos , Quimioprevenção/métodos , Hansenostáticos/uso terapêutico , Hanseníase/prevenção & controle , Vacina BCG/imunologia , Controle de Doenças Transmissíveis/métodos
16.
Infect Immun ; 82(9): 3900-9, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25001602

RESUMO

Leprosy remains a major global health problem and typically occurs in regions in which tuberculosis is endemic. Vaccines are needed that protect against both infections and do so better than the suboptimal Mycobacterium bovis BCG vaccine. Here, we evaluated rBCG30, a vaccine previously demonstrated to induce protection superior to that of BCG against Mycobacterium tuberculosis and Mycobacterium bovis challenge in animal models, for efficacy against Mycobacterium leprae challenge in a murine model of leprosy. rBCG30 overexpresses the M. tuberculosis 30-kDa major secretory protein antigen 85B, which is 85% homologous with the M. leprae homolog (r30ML). Mice were sham immunized or immunized intradermally with BCG or rBCG30 and challenged 2.5 months later by injection of viable M. leprae into each hind footpad. After 7 months, vaccine efficacy was assessed by enumerating the M. leprae bacteria per footpad. Both BCG and rBCG30 induced significant protection against M. leprae challenge. In the one experiment in which a comparison between BCG and rBCG30 was feasible, rBCG30 induced significantly greater protection than did BCG. Immunization of mice with purified M. tuberculosis or M. leprae antigen 85B also induced protection against M. leprae challenge but less so than BCG or rBCG30. Notably, boosting rBCG30 with M. tuberculosis antigen 85B significantly enhanced r30ML-specific immune responses, substantially more so than boosting BCG, and significantly augmented protection against M. leprae challenge. Thus, rBCG30, a vaccine that induces improved protection against M. tuberculosis, induces cross-protection against M. leprae that is comparable or potentially superior to that induced by BCG, and boosting rBCG30 with antigen 85B further enhances immune responses and protective efficacy.


Assuntos
Aciltransferases/imunologia , Antígenos de Bactérias/imunologia , Vacina BCG/imunologia , Proteínas de Bactérias/imunologia , Proteção Cruzada/imunologia , Mycobacterium leprae/imunologia , Mycobacterium tuberculosis/imunologia , Vacinas contra a Tuberculose/imunologia , Animais , Linfócitos T CD4-Positivos/imunologia , Feminino , Imunização/métodos , Hanseníase/imunologia , Hanseníase/prevenção & controle , Camundongos , Camundongos Endogâmicos BALB C , Mycobacterium bovis/imunologia , Tuberculose/imunologia , Tuberculose/prevenção & controle , Vacinação/métodos
17.
BMC Infect Dis ; 13: 456, 2013 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-24088534

RESUMO

BACKGROUND: Despite almost 30 years of effective chemotherapy with MDT, the global new case detection rate of leprosy has remained quite constant over the past years. New tools and methodologies are necessary to interrupt the transmission of M. leprae. Single-dose rifampicin (SDR) has been shown to prevent 57% of incident cases of leprosy in the first two years, when given to contacts of newly diagnosed cases. Immunization of contacts with BCG has been less well documented, but appears to have a preventive effect lasting up to 9 years. However, one major disadvantage is the occurrence of excess cases within the first year after immunization. The objective of this study is to examine the effect of chemoprophylaxis with SDR and immunoprophylaxis with BCG on the clinical outcome as well as on host immune responses and gene expression profiles in contacts of newly diagnosed leprosy patients. We hypothesize that the effects of both interventions may be complementary, causing the combined preventive outcome to be significant and long-lasting. METHODS/DESIGN: Through a cluster randomized controlled trial we compare immunization with BCG alone with BCG plus SDR in contacts of new leprosy cases. Contact groups of around 15 persons will be established for each of the 1300 leprosy patients included in the trial, resulting in approximately 20,000 contacts in total. BCG will be administered to the intervention group followed by SDR, 2 months later. The control group will receive BCG only. In total 10,000 contacts will be included in both intervention arms over a 2-year period. Follow-up will take place one year as well as two years after intake. The primary outcome is the occurrence of clinical leprosy within two years. Simultaneously with vaccination and SDR, blood samples for in vitro analyses will be obtained from 300 contacts participating in the trial to determine the effect of these chemo- and immunoprophylactic interventions on immune and genetic host parameters. DISCUSSION: Combined chemoprophylaxis and immunoprophylaxis is potentially a very powerful and innovative tool aimed at contacts of leprosy patients that could reduce the transmission of M. leprae markedly. The trial intends to substantiate this potential preventive effect. Evaluation of immune and genetic biomarker profiles will allow identification of pathogenic versus (BCG-induced) protective host biomarkers and could lead to effective prophylactic interventions for leprosy using optimized tools for identification of individuals who are most at risk of developing disease. TRIAL REGISTRATION: Netherlands Trial Register: NTR3087.


Assuntos
Vacina BCG/administração & dosagem , Hanseníase/tratamento farmacológico , Rifampina/administração & dosagem , Vacina BCG/efeitos adversos , Vacina BCG/imunologia , Quimioprevenção , Quimioterapia Combinada , Humanos , Hanseníase/imunologia , Hanseníase/microbiologia , Hanseníase/prevenção & controle , Mycobacterium leprae/efeitos dos fármacos , Mycobacterium leprae/fisiologia , Países Baixos , Rifampina/efeitos adversos
18.
PLoS One ; 8(7): e66115, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23861742

RESUMO

Although the effectiveness of BCG vaccination in preventing adult pulmonary tuberculosis (TB) has been highly variable, epidemiologic studies have suggested that BCG provides other general health benefits to vaccinees including reducing the impact of asthma, leprosy, and possibly malaria. To further evaluate whether BCG immunization protects against malarial parasitemia and to define molecular correlates of this non-specific immunity, mice were vaccinated with BCG and then challenged 2 months later with asexual blood stage Plasmodium yoelii 17XNL (PyNL) parasites. Following challenge with PyNL, significant decreases in parasitemia were observed in BCG vaccinated mice relative to naïve controls. To identify immune molecules that may be associated with the BCG-induced protection, gene expression was evaluated by RT-PCR in i) naïve controls, ii) BCG-vaccinated mice, iii) PyNL infected mice and iv) BCG vaccinated/PyNL infected mice at 0, 1, 5, and 9 days after the P. yoelii infection. The expression results showed that i) BCG immunization induces the expression of at least 18 genes including the anti-microbial molecules lactoferrin, eosinophil peroxidase, eosinophil major basic protein and the cathelicidin-related antimicrobial peptide (CRAMP); ii) an active PyNL infection suppresses the expression of important immune response molecules; and iii) the extent of PyNL-induced suppression of specific genes is reduced in BCG-vaccinated/PyNL infected mice. To validate the gene expression data, we demonstrated that pre-treatment of malaria parasites with lactoferrin or the cathelicidin LL-37 peptide decreases the level of PyNL parasitemias in mice. Overall, our study suggests that BCG vaccination induces the expression of non-specific immune molecules including antimicrobial peptides which may provide an overall benefit to vaccinees by limiting infections of unrelated pathogens such as Plasmodium parasites.


Assuntos
Vacina BCG/imunologia , Expressão Gênica/efeitos dos fármacos , Imunidade Inata/efeitos dos fármacos , Malária/prevenção & controle , Plasmodium yoelii/efeitos dos fármacos , Vacinação , Animais , Peptídeos Catiônicos Antimicrobianos , Vacina BCG/administração & dosagem , Catelicidinas/genética , Catelicidinas/imunologia , Catelicidinas/farmacologia , Proteína Básica Maior de Eosinófilos/genética , Proteína Básica Maior de Eosinófilos/imunologia , Peroxidase de Eosinófilo/genética , Peroxidase de Eosinófilo/imunologia , Feminino , Expressão Gênica/imunologia , Lactoferrina/genética , Lactoferrina/imunologia , Lactoferrina/farmacologia , Malária/imunologia , Malária/parasitologia , Camundongos , Camundongos Endogâmicos C57BL , Plasmodium yoelii/imunologia
19.
Artigo em Inglês | MEDLINE | ID: mdl-23740009

RESUMO

Leprosy is a disease caused by Mycobacterium leprae that carries a high risk of disability, making early diagnosis mandatory. This study aimed to determine the applicability of anti-PGL-1 IgM antibody detection, using the ML FLOW technique, as an assistant tool for the detection of leprosy infection in asymptomatic household contacts (AHHC) of multibacillary leprosy index cases from Midwest Brazil. Serological changes induced by the prophylaxis of these household contacts with Bacillus Calmette-Guérin (BCG) were also verified. A total of 91 AHHC were assessed, among which, 18.68% (n = 17) presented both positive bacilloscopy and positive anti-PGL-1 IgM serology. Positivity concordance between these two laboratorial exams (Kappa Index = 1; p < 0.001) was indicated, however, one case did not demonstrate concordance between the semiquantitative assessment of anti-PGL-1 IgM and the bacilloscopy index (Kappa Index = 0.96; p < 0.001). Among the 17 AHHC with positive bacilloscopy, eight were reassessed after prophylaxis with BCG and two of them presented negative anti-PGL-1 IgM serology, being these patients who had presented a bacilloscopy index of < 2[+] in the initial assessment. This study shows that anti-PGL-1 IgM detection may be used as a tool to determine the bacillary load in AHHC and to detect immune changes related to prophylaxis by nonspecific vaccination.


Assuntos
Adjuvantes Imunológicos , Anticorpos Antibacterianos/sangue , Antígenos de Bactérias/imunologia , Vacina BCG/imunologia , Glicolipídeos/imunologia , Hanseníase Multibacilar/diagnóstico , Mycobacterium leprae/imunologia , Adjuvantes Imunológicos/administração & dosagem , Adolescente , Adulto , Vacina BCG/administração & dosagem , Características da Família , Feminino , Humanos , Hanseníase Multibacilar/imunologia , Hanseníase Multibacilar/prevenção & controle , Masculino , Valor Preditivo dos Testes , Sensibilidade e Especificidade , Adulto Jovem
20.
Rev. Inst. Med. Trop. Säo Paulo ; 55(3): 173-177, May-Jun/2013. tab
Artigo em Inglês | LILACS | ID: lil-674680

RESUMO

Leprosy is a disease caused by Mycobacterium leprae that carries a high risk of disability, making early diagnosis mandatory. This study aimed to determine the applicability of anti-PGL-1 IgM antibody detection, using the ML FLOW technique, as an assistant tool for the detection of leprosy infection in asymptomatic household contacts (AHHC) of multibacillary leprosy index cases from Midwest Brazil. Serological changes induced by the prophylaxis of these household contacts with Bacillus Calmette-Guérin (BCG) were also verified. A total of 91 AHHC were assessed, among which, 18.68% (n = 17) presented both positive bacilloscopy and positive anti-PGL-1 IgM serology. Positivity concordance between these two laboratorial exams (Kappa Index = 1; p < 0.001) was indicated, however, one case did not demonstrate concordance between the semiquantitative assessment of anti-PGL-1 IgM and the bacilloscopy index (Kappa Index = 0.96; p < 0.001). Among the 17 AHHC with positive bacilloscopy, eight were reassessed after prophylaxis with BCG and two of them presented negative anti-PGL-1 IgM serology, being these patients who had presented a bacilloscopy index of < 2[+] in the initial assessment. This study shows that anti-PGL-1 IgM detection may be used as a tool to determine the bacillary load in AHHC and to detect immune changes related to prophylaxis by nonspecific vaccination.


A hanseníase é doença causada pelo Mycobacterium leprae, apresentando elevado potencial incapacitante, o que torna indispensável seu diagnóstico precoce. O estudo visa determinar a aplicabilidade da detecção de anticorpos anti-PGL1-IgM por meio da técnica do ML FLOW como ferramenta adjuvante ao diagnóstico de hanseníase em contatos domiciliares assintomáticos (AHHC) de pacientes multibacilares procedentes da região Centro-Oeste do Brasil, bem como, documentar o comportamento sorológico após a profilaxia com a vacina Bacillus Calmette-Guérin (BCG). Foram avaliados 91 AHHC atendidos no Hospital Universitário de Brasília - Brasil, dos quais 18,68% (n = 17) apresentaram positividade para baciloscopia e anti-PGL1-IgM, totalizando uma concordância completa entre os dois grupos (Índice Kappa = 1; p < 0,001). Em apenas um dos casos não observou-se concordância entre a avaliação semi-quantitativa do anti-PGL1-IgM e índice baciloscópico (Índice Kappa = 0,96; p < 0,001). Oito dos 17 AHHC com baciloscopia positiva foram reavaliados após profilaxia com BCG e apenas dois apresentaram negativação dos títulos anti-PGL1-IgM, sendo tais casos correspondentes aos que haviam apresentado índice baciloscópico menor do que 2[+] na avaliação inicial. O estudo corrobora o potencial do anti-PGL1-IgM como ferramenta de predição da carga bacilar em AHHC da região Centro-Oeste do Brasil, e surpreende alterações imunes relacionadas à profilaxia obtida pela vacinação não específica com BCG.


Assuntos
Adolescente , Adulto , Feminino , Humanos , Masculino , Adulto Jovem , Adjuvantes Imunológicos , Anticorpos Antibacterianos/sangue , Antígenos de Bactérias/imunologia , Vacina BCG/imunologia , Glicolipídeos/imunologia , Hanseníase Multibacilar/diagnóstico , Mycobacterium leprae/imunologia , Adjuvantes Imunológicos/administração & dosagem , Vacina BCG/administração & dosagem , Características da Família , Hanseníase Multibacilar/imunologia , Hanseníase Multibacilar/prevenção & controle , Valor Preditivo dos Testes , Sensibilidade e Especificidade
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