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1.
BMC Infect Dis ; 20(1): 750, 2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33050903

RESUMO

BACKGROUND: Tuberculosis (TB) is caused by Mycobacterium tuberculosis complex (MTBC). Mapping the genetic diversity of MTBC in high TB burden country like Ethiopia is important to understand principles of the disease transmission and to strengthen the regional TB control program. The aim of this study was to investigate the genetic diversity of Mycobacterium tuberculosis complex (MTBC) isolates circulating in the South Omo, southern Ethiopia. METHODS: MTBC isolates (N = 156) were genetically analyzed using spacer oligotyping (spoligotyping) and mycobacterial interspersed repetitive unit-variable number of tandem repeat (MIRU-VNTR) typing. Major lineages and lineages were identified using MTBC databases. Logistic regression was used to correlate patient characteristics with strain clustering. RESULTS: The study identified Euro-American (EA), East-African-Indian (EAI), Indo-Oceanic (IO), Lineage_7/Aethiops vertus, Mycobacterium bovis and Mycobacterium africanum major lineages in proportions of 67.3% (105/156), 22.4% (35/156), 6.4% (10/156), 1.9% (3/156), 1.3% (2/156) and 0.6% (1/156), respectively. Lineages identified were Delhi/CAS 23.9% (37/155), Ethiopia_2 20.6% (32/155), Haarlem 14.2% (22/155), URAL 14.2%(22/155), Ethiopia_3 8.4% (13/155), TUR 6.5% (10/155), Lineage_7/Aethiops vertus 1.9% (3/155), Bovis 1.3% (2/155), LAM 1.3% (2/155), EAI 0.6% (1/155), X 0.6% (1/155) and Ethiopia H37Rv-like strain 0.6% (1/155). Of the genotyped isolates 5.8% (9/155) remained unassigned. The recent transmission index (RTI) was 3.9%. Orphan strains compared to shared types (AOR: 0.09, 95% CI: 0.04-0.25) were associated with reduced odds of clustering. The dominant TB lineage in pastoral areas was EAI and in non-pastoral areas was EA. CONCLUSION: The epidemiological data, highly diverse MTBC strains and a low RTI in South Omo, provide information contributing to the TB Control Program of the country.


Assuntos
Variação Genética , Mycobacterium bovis/genética , Mycobacterium tuberculosis/genética , Tuberculose Pulmonar/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Etiópia/epidemiologia , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Repetições Minissatélites/genética , Epidemiologia Molecular , Reação em Cadeia da Polimerase Multiplex , Mycobacterium bovis/isolamento & purificação , Mycobacterium tuberculosis/isolamento & purificação , Escarro/microbiologia , Tuberculose Pulmonar/microbiologia , Adulto Jovem
2.
Vet Rec ; 187(8): 323, 2020 10 17.
Artigo em Inglês | MEDLINE | ID: mdl-33060234
3.
BMC Infect Dis ; 20(1): 711, 2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-32993535

RESUMO

BACKGROUND: Mycobacterium bovis could infect patients with immunodeficiency or immunosuppressive conditions via Bacillus Calmette-Guérin (BCG) vaccination. Tuberculosis-related hemophagocytic syndrome (HPS) is reported, but not HPS caused by Mycobacterium bovis in children. CASE PRESENTATION: A 4-month Chinese boy presented fever and cough. The initial laboratory investigation showed the lymphocyte count of 0.97 × 109/L, which decreased gradually. HPS was diagnosed based on the test results that fulfilled the HLH-2004 criteria. In addition, Mycobacterium tuberculosis complex was detected from his peripheral blood via metagenomic next-generation sequencing (mNGS) and M. bovis was identified by polymerase chain reaction-reverse dot blot (PCR-RDB). Thus, the patient was treated with Isoniazid, Rifampin, and Pyrazinamide, but not improved. However, parents refused to accept further therapy, and was discharged on the day 12 of admission. To confirm the pathogenesis, genetic analysis was performed. Mutation in the interleukin-2 receptor subunit gamma gene: Exon 6: c.854G > A; p. Arg285Gln was detected in the patient and the mother, which could underlie X-linked severe combined immunodeficiency. CONCLUSIONS: A boy with X-SCID was diagnosed with M. bovis-associated HPS, emphasizing that X-SCID should be considered when M. bovis is detected in a male infant with low lymphocyte counts.


Assuntos
Linfo-Histiocitose Hemofagocítica/complicações , Mycobacterium bovis/genética , Mycobacterium tuberculosis/genética , Tuberculose/complicações , Doenças por Imunodeficiência Combinada Ligada ao Cromossomo X/complicações , Antibióticos Antituberculose/uso terapêutico , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Lactente , Subunidade gama Comum de Receptores de Interleucina/genética , Isoniazida/uso terapêutico , Linfo-Histiocitose Hemofagocítica/tratamento farmacológico , Linfo-Histiocitose Hemofagocítica/microbiologia , Masculino , Mutação , Alta do Paciente , Reação em Cadeia da Polimerase , Pirazinamida/uso terapêutico , Rifampina/uso terapêutico , Resultado do Tratamento , Tuberculose/tratamento farmacológico , Tuberculose/microbiologia
4.
BMC Infect Dis ; 20(1): 708, 2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-32993546

RESUMO

BACKGROUND: Intravesical administration of Bacillus Calmette-Guérin (BCG) has proven useful for treatment and prevention of recurrence of superficial bladder cancer and in situ carcinoma. However, fatal side effects such as disseminated infections may occur. Early diagnosis and accurate therapy for interstitial pneumonitis (IP) are important because exacerbation of IP triggered by infections is the major cause of death. Although some fatality reports have suggested newly appeared IP after intravesical BCG treatment, to our knowledge, there are no reports which have demonstrated acute exacerbation of existing IP. Moreover, autopsy is lacking in previous reports. We report the case of a patient with fatal IP exacerbation after BCG instillation and the pathological findings of the autopsy. CASE PRESENTATION: A 77-year-old man with a medical history of IP was referred to our hospital because of fever and malaise. He had received an intravesical injection of BCG 1 day before the admission. His fever reduced after the use of antituberculosis drugs, so he was discharged home. He was referred to our hospital again because of a high fever 7 days after discharge. On hospitalisation, he showed high fever and systemic exanthema. Hepatosplenomegaly and myelosuppression were also observed. Biopsies revealed multiple epithelioid cell granulomas with Langhans giant cells of the liver and bone marrow. Biopsy DNA analyses of Mycobacterium bovis in the bone marrow, sputum, and blood were negative. His oxygen demand worsened drastically, and the ground-glass shadow expanded on the computed tomography scan. He was diagnosed with acute exacerbation of existing IP. We recommenced the antituberculosis drugs with steroid pulse therapy, but he died on day 35 because of respiratory failure. The autopsy revealed a diffuse appearance of multiple epithelioid cell granulomas with Langhans giant cells in multiple organs, although BCG was not evident. CONCLUSIONS: We report the first case of acute exacerbation of chronic IP by BCG infection. This is also the first case of autopsy of a patient with acute exacerbation of existing IP induced by intravesical BCG treatment. Whether the trigger of acute IP exacerbation is infection or hypersensitivity to BCG is still controversial, because pathological evidence confirming BCG infection is lacking. Physicians who administer BCG against bladder cancer should be vigilant for acute exacerbation of IP.


Assuntos
Antituberculosos/uso terapêutico , Vacina BCG/efeitos adversos , Doenças Pulmonares Intersticiais/tratamento farmacológico , Doenças Pulmonares Intersticiais/etiologia , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Infecções por Mycobacterium não Tuberculosas/etiologia , Esteroides/uso terapêutico , Exacerbação dos Sintomas , Administração Intravesical , Idoso , Autopsia , Vacina BCG/administração & dosagem , Vacina BCG/uso terapêutico , Carcinoma in Situ/tratamento farmacológico , Carcinoma in Situ/prevenção & controle , Evolução Fatal , Humanos , Doenças Pulmonares Intersticiais/microbiologia , Masculino , Infecções por Mycobacterium não Tuberculosas/diagnóstico , Mycobacterium bovis/genética , Resultados Negativos , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/prevenção & controle , Pulsoterapia , Resultado do Tratamento , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/prevenção & controle
6.
Vaccine ; 38(41): 6352-6356, 2020 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-32863070

RESUMO

The world is facing the rising emergency of SARS-CoV-2. The outbreak of COVID-19 has caused a global public health and economic crisis.Recent epidemiological studies have shown that a possible association of BCG vaccination program with decreased COVID-19-related risks, suggesting that BCG may provide protection against COVID-19. Non-specific protection against viral infections is considered as a main mechanism of BCG and clinical trials to determine whether BCG vaccine can protect healthcare workers from the COVID-19 are currently underway. We hypothesized that BCG may carry similar T cell epitopes with SARS-CoV-2 and evaluated the hypothesis by utilizing publicly available database and computer algorithms predicting human leukocyte antigen (HLA) class I-binding peptides. We foundthatBCG contains similar 9-amino acid sequences with SARS-CoV-2. These closely-related peptides had moderate to high binding affinity for multiple common HLA class I molecules, suggesting that cross-reactive T cells against SARS-CoV-2 could be generated by BCG vaccination.


Assuntos
Vacina BCG/imunologia , Betacoronavirus/imunologia , Linfócitos T CD8-Positivos/imunologia , Infecções por Coronavirus/prevenção & controle , Epitopos de Linfócito T/imunologia , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Sequência de Aminoácidos/genética , Betacoronavirus/genética , Reações Cruzadas/imunologia , Epitopos de Linfócito T/genética , Antígenos de Histocompatibilidade Classe I/imunologia , Humanos , Mycobacterium bovis/genética , Mycobacterium bovis/imunologia , Vacinas Virais/imunologia
7.
Vaccine ; 38(41): 6352-6356, 2020 09 22.
Artigo em Inglês | MEDLINE | ID: covidwho-723380

RESUMO

The world is facing the rising emergency of SARS-CoV-2. The outbreak of COVID-19 has caused a global public health and economic crisis.Recent epidemiological studies have shown that a possible association of BCG vaccination program with decreased COVID-19-related risks, suggesting that BCG may provide protection against COVID-19. Non-specific protection against viral infections is considered as a main mechanism of BCG and clinical trials to determine whether BCG vaccine can protect healthcare workers from the COVID-19 are currently underway. We hypothesized that BCG may carry similar T cell epitopes with SARS-CoV-2 and evaluated the hypothesis by utilizing publicly available database and computer algorithms predicting human leukocyte antigen (HLA) class I-binding peptides. We foundthatBCG contains similar 9-amino acid sequences with SARS-CoV-2. These closely-related peptides had moderate to high binding affinity for multiple common HLA class I molecules, suggesting that cross-reactive T cells against SARS-CoV-2 could be generated by BCG vaccination.


Assuntos
Vacina BCG/imunologia , Betacoronavirus/imunologia , Linfócitos T CD8-Positivos/imunologia , Infecções por Coronavirus/prevenção & controle , Epitopos de Linfócito T/imunologia , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Sequência de Aminoácidos/genética , Betacoronavirus/genética , Reações Cruzadas/imunologia , Epitopos de Linfócito T/genética , Antígenos de Histocompatibilidade Classe I/imunologia , Humanos , Mycobacterium bovis/genética , Mycobacterium bovis/imunologia , Vacinas Virais/imunologia
8.
Cytokine Growth Factor Rev ; 54: 32-42, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32747157

RESUMO

The seventh human coronavirus SARS-CoV2 belongs to the cluster of extremely pathogenic coronaviruses including SARS-CoV and MERS-CoV, which can cause fatal lower respiratory tract infection. Likewise, SARS-CoV2 infection can be fatal as the disease advances to pneumonia, followed by acute respiratory distress syndrome (ARDS). The development of lethal clinical symptons is associated with an exaggerated production of inflammatory cytokines, referred to as the cytokine storm, is a consequence of a hyperactivated immune response aginst the infection. In this article, we discuss the pathogenic consequences of the cytokine storm and its relationship with COVID-19 associated risk factors. The increased pro-inflammatory immune status in patients with risk factors (diabetes, hypertension, cardiovascular disease, COPD) exacerbates the Cytokine-storm of COVID-19 into a 'Cytokine Super Cyclone'. We also evaluate the antiviral immune responses provided by BCG vaccination and the potential role of 'trained immunity' in early protection against SARS-CoV2.


Assuntos
Vacina BCG/uso terapêutico , Infecções por Coronavirus/prevenção & controle , Síndrome da Liberação de Citocina/prevenção & controle , Citocinas/sangue , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Antivirais/uso terapêutico , Betacoronavirus/imunologia , Doenças Cardiovasculares/patologia , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/imunologia , Síndrome da Liberação de Citocina/imunologia , Síndrome da Liberação de Citocina/patologia , Diabetes Mellitus/patologia , Humanos , Hipertensão/patologia , Coronavírus da Síndrome Respiratória do Oriente Médio/imunologia , Mycobacterium bovis/imunologia , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/imunologia , Doença Pulmonar Obstrutiva Crônica/patologia , Fatores de Risco , Síndrome Respiratória Aguda Grave/imunologia , Vacinação
9.
Vaccine ; 38(41): 6374-6380, 2020 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-32798142

RESUMO

The rapid spread of the Coronavirus pandemic and its significant health and social impact urges the search for effective and readily available solutions to mitigate the damages. Thus, evaluating the effectiveness of existing vaccines like Bacillus Calmette-Guérin (BCG) has attracted attention. The aim of this review was evidence synthesis on the effect of BCG vaccine in preventing severe infectious respiratory disease including COVD-19, but not tuberculosis. We considered studies conducted on human participants of any study design from any country setting that were published in Enlgish. We did a systematic literature search in MEDLINE, Scopus and Google scholar databases and a free search on Google. The identified studies were appraised and relevant data were extracted using Joanna Briggs Institute tools. The extracted findings were synthesized with tables and narrative summary. Nine studies met the inclusion criteria. The findings indicated that BCG vaccine has a strong protective effect against both upper and lower acute respiratory tract infections. For instance in countries with universal BCG vaccination policy, the incidence of COVID-19 was lower compared to the counterparts. Addtionally, BCG vaccine was found to protect against infections like lethal influenza A virus, pandemic influenza (H1N1), and other acute respiratory tract infections. BCG improved the human body's immune response involving antigen-specific T cells and memory cells. It also induced adaptive functional reprogramming of mononuclear phagocytes that induce protective effects against different respiratory infections other than tuberculosis. In countries with universal BCG vaccination, the incidence and death from acute respiratory viral infection including COVID - 19 is significantly low. However, there is an urgent need for further evidence from well-designed studies to understand the possible role of BCG vaccination over time and across age groups, its possible benefits in special populations such as health workers and cost-savings related to a policy of universal BCG vaccination.


Assuntos
Vacina BCG/imunologia , Betacoronavirus/imunologia , Infecções por Coronavirus/prevenção & controle , Mycobacterium bovis/imunologia , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Anticorpos Antivirais/imunologia , Humanos , Vírus da Influenza A Subtipo H1N1/imunologia , Influenza Humana/prevenção & controle , Tuberculose Pulmonar/prevenção & controle , Vacinação
10.
Cytokine Growth Factor Rev ; 54: 32-42, 2020 08.
Artigo em Inglês | MEDLINE | ID: covidwho-623795

RESUMO

The seventh human coronavirus SARS-CoV2 belongs to the cluster of extremely pathogenic coronaviruses including SARS-CoV and MERS-CoV, which can cause fatal lower respiratory tract infection. Likewise, SARS-CoV2 infection can be fatal as the disease advances to pneumonia, followed by acute respiratory distress syndrome (ARDS). The development of lethal clinical symptons is associated with an exaggerated production of inflammatory cytokines, referred to as the cytokine storm, is a consequence of a hyperactivated immune response aginst the infection. In this article, we discuss the pathogenic consequences of the cytokine storm and its relationship with COVID-19 associated risk factors. The increased pro-inflammatory immune status in patients with risk factors (diabetes, hypertension, cardiovascular disease, COPD) exacerbates the Cytokine-storm of COVID-19 into a 'Cytokine Super Cyclone'. We also evaluate the antiviral immune responses provided by BCG vaccination and the potential role of 'trained immunity' in early protection against SARS-CoV2.


Assuntos
Vacina BCG/uso terapêutico , Infecções por Coronavirus/prevenção & controle , Síndrome da Liberação de Citocina/prevenção & controle , Citocinas/sangue , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Antivirais/uso terapêutico , Betacoronavirus/imunologia , Doenças Cardiovasculares/patologia , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/imunologia , Síndrome da Liberação de Citocina/imunologia , Síndrome da Liberação de Citocina/patologia , Diabetes Mellitus/patologia , Humanos , Hipertensão/patologia , Coronavírus da Síndrome Respiratória do Oriente Médio/imunologia , Mycobacterium bovis/imunologia , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/imunologia , Doença Pulmonar Obstrutiva Crônica/patologia , Fatores de Risco , Síndrome Respiratória Aguda Grave/imunologia , Vacinação
12.
Cytokine Growth Factor Rev ; 54: 32-42, 2020 08.
Artigo em Inglês | MEDLINE | ID: covidwho-694176

RESUMO

The seventh human coronavirus SARS-CoV2 belongs to the cluster of extremely pathogenic coronaviruses including SARS-CoV and MERS-CoV, which can cause fatal lower respiratory tract infection. Likewise, SARS-CoV2 infection can be fatal as the disease advances to pneumonia, followed by acute respiratory distress syndrome (ARDS). The development of lethal clinical symptons is associated with an exaggerated production of inflammatory cytokines, referred to as the cytokine storm, is a consequence of a hyperactivated immune response aginst the infection. In this article, we discuss the pathogenic consequences of the cytokine storm and its relationship with COVID-19 associated risk factors. The increased pro-inflammatory immune status in patients with risk factors (diabetes, hypertension, cardiovascular disease, COPD) exacerbates the Cytokine-storm of COVID-19 into a 'Cytokine Super Cyclone'. We also evaluate the antiviral immune responses provided by BCG vaccination and the potential role of 'trained immunity' in early protection against SARS-CoV2.


Assuntos
Vacina BCG/uso terapêutico , Infecções por Coronavirus/prevenção & controle , Síndrome da Liberação de Citocina/prevenção & controle , Citocinas/sangue , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Antivirais/uso terapêutico , Betacoronavirus/imunologia , Doenças Cardiovasculares/patologia , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/imunologia , Síndrome da Liberação de Citocina/imunologia , Síndrome da Liberação de Citocina/patologia , Diabetes Mellitus/patologia , Humanos , Hipertensão/patologia , Coronavírus da Síndrome Respiratória do Oriente Médio/imunologia , Mycobacterium bovis/imunologia , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/imunologia , Doença Pulmonar Obstrutiva Crônica/patologia , Fatores de Risco , Síndrome Respiratória Aguda Grave/imunologia , Vacinação
13.
Vaccine ; 38(41): 6374-6380, 2020 09 22.
Artigo em Inglês | MEDLINE | ID: covidwho-704025

RESUMO

The rapid spread of the Coronavirus pandemic and its significant health and social impact urges the search for effective and readily available solutions to mitigate the damages. Thus, evaluating the effectiveness of existing vaccines like Bacillus Calmette-Guérin (BCG) has attracted attention. The aim of this review was evidence synthesis on the effect of BCG vaccine in preventing severe infectious respiratory disease including COVD-19, but not tuberculosis. We considered studies conducted on human participants of any study design from any country setting that were published in Enlgish. We did a systematic literature search in MEDLINE, Scopus and Google scholar databases and a free search on Google. The identified studies were appraised and relevant data were extracted using Joanna Briggs Institute tools. The extracted findings were synthesized with tables and narrative summary. Nine studies met the inclusion criteria. The findings indicated that BCG vaccine has a strong protective effect against both upper and lower acute respiratory tract infections. For instance in countries with universal BCG vaccination policy, the incidence of COVID-19 was lower compared to the counterparts. Addtionally, BCG vaccine was found to protect against infections like lethal influenza A virus, pandemic influenza (H1N1), and other acute respiratory tract infections. BCG improved the human body's immune response involving antigen-specific T cells and memory cells. It also induced adaptive functional reprogramming of mononuclear phagocytes that induce protective effects against different respiratory infections other than tuberculosis. In countries with universal BCG vaccination, the incidence and death from acute respiratory viral infection including COVID - 19 is significantly low. However, there is an urgent need for further evidence from well-designed studies to understand the possible role of BCG vaccination over time and across age groups, its possible benefits in special populations such as health workers and cost-savings related to a policy of universal BCG vaccination.


Assuntos
Vacina BCG/imunologia , Betacoronavirus/imunologia , Infecções por Coronavirus/prevenção & controle , Mycobacterium bovis/imunologia , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Anticorpos Antivirais/imunologia , Humanos , Vírus da Influenza A Subtipo H1N1/imunologia , Influenza Humana/prevenção & controle , Tuberculose Pulmonar/prevenção & controle , Vacinação
14.
Rev Med Liege ; 75(7-8): 518-520, 2020 Jul.
Artigo em Francês | MEDLINE | ID: mdl-32779902

RESUMO

Bladder cancer (urothelial carcinoma in 90 % of cases) is the most common neoplasia of the urinary tract. Superficial carcinoma represents 70-80 % of bladder cancers. The treatment of these tumours includes, after transuretral resection, intravesical Bacillus Calmette-Guerin (BCG) instillation therapy. This treatment constitutes, by its immune-mediated anti-tumoral action, the first step of immunotherapy in cancer. Severe complications (granulomatosis, hypersensitivity pneumonitis or orchitis) are rare (0.5-2 %). Here we report a complex case of pulmonary granulomatosis secondary to BCG therapy. This is a 74-year-old male, treated for superficial bladder carcinoma by transuretral resection (pT1G3) and then endovesical instillations of BCG therapy for two months. Two years later, a new transuretral resection shows an infiltrating urothelial carcinoma pT2G3. The extension balance finds a persistent micro-nodular pulmonary infiltrate. A broncho-alveolar lavage is then realised but no mycobacteria was found. A surgical biopsy of a nodule is performed and revealed a histiocytic reaction without any neoplastic element. Detection of Mycobacterium tuberculosis by Polymerase Chain Reaction (PCR) was finally positive. In the absence of a secondary lesion, the patient had a cysto-prostatectomy and began a tritherapy against tuberculosis. Post-BCG therapy granulomatosis is a rare complication but should remain a differential diagnosis in front of the appearance of pulmonary nodes in patients who have received posttransuretral resection BCG instillations. Mycobacterial DNA PCR research remains the most sensitive examination.


Assuntos
Mycobacterium bovis , Tuberculose Miliar , Tuberculose Pulmonar , Neoplasias da Bexiga Urinária/tratamento farmacológico , Administração Intravesical , Idoso , Humanos , Masculino
15.
Int J Infect Dis ; 97: 117-125, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32497805

RESUMO

BACKGROUND: Disseminated Bacillus Calmette-Guérin (BCG) disease (BCGosis) is a classical feature of children with primary immunodeficiency disorders (PIDs). METHODS: A 15-year retrospective review was conducted in KK Women's and Children's Hospital in Singapore, from January 2003 to October 2017. RESULTS: Ten patients were identified, the majority male (60.0%). The median age at presentation of symptoms of BCG infections was 3.8 (0.8 - 7.4) months. All the patients had likely underlying PIDS - four with Severe Combined Immunodeficiency (SCID), three with Mendelian Susceptibility to Mycobacterial Diseases (MSMD), one with Anhidrotic Ectodermal Dysplasia with Primary Immunodeficiency (EDA-ID), one with combined immunodeficiency (CID), and one with STAT-1 gain-of-function mutation. Definitive BCGosis was confirmed in all patients by the identification of Mycobacterium bovis subsp BCG from microbiological cultures. The susceptibility profiles of Mycobacterium bovis subsp BCG are as follows: Rifampicin (88.9%), Isoniazid (44.47%), Ethambutol (100.0%), Streptomycin (100.0%), Kanamycin (100.0%), Ethionamide (25.0%), and Ofloxacin (100.0%). Four patients (40.0%) received a three-drug regimen. Five patients (50.0%) underwent hematopoietic stem cell transplant (HSCT), of which three (60%) have recovered. Overall mortality was 50.0%. CONCLUSION: Disseminated BCG disease (BCGosis) should prompt immunology evaluation to determine the diagnosis of the immune defect. A three-drug regimen is adequate for treatment if the patient undergoes early HSCT.


Assuntos
Vacina BCG/efeitos adversos , Mycobacterium bovis , Doenças da Imunodeficiência Primária/complicações , Tuberculose/etiologia , Vacina BCG/uso terapêutico , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Doenças da Imunodeficiência Primária/terapia , Estudos Retrospectivos , Singapura , Tuberculose/tratamento farmacológico , Tuberculose/etnologia
16.
mBio ; 11(3)2020 06 19.
Artigo em Inglês | MEDLINE | ID: covidwho-607036

RESUMO

We propose the concept that administration of an unrelated live attenuated vaccine, such as MMR (measles, mumps, rubella), could serve as a preventive measure against the worst sequelae of coronavirus disease 2019 (COVID-19). There is mounting evidence that live attenuated vaccines provide nonspecific protection against lethal infections unrelated to the target pathogen of the vaccine by inducing "trained" nonspecific innate immune cells for improved host responses against subsequent infections. Mortality in COVID-19 cases is strongly associated with progressive lung inflammation and eventual sepsis. Vaccination with MMR in immunocompetent individuals has no contraindications and may be especially effective for health care workers who can easily be exposed to COVID-19. Following the lead of other countries conducting clinical trials with the live attenuated Mycobacterium bovis BCG (BCG) vaccine under a similar concept, a clinical trial with MMR in high-risk populations may provide a "low-risk-high-reward" preventive measure in saving lives during this unprecedented COVID-19 pandemic.


Assuntos
Vacina BCG/imunologia , Betacoronavirus/imunologia , Infecções por Coronavirus/prevenção & controle , Proteção Cruzada/imunologia , Vacina contra Sarampo-Caxumba-Rubéola/imunologia , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Vacinas Atenuadas/imunologia , Ensaios Clínicos como Assunto , Infecções por Coronavirus/patologia , Humanos , Sarampo/imunologia , Caxumba/imunologia , Mycobacterium bovis/imunologia , Pneumonia Viral/patologia , Rubéola (Sarampo Alemão)/imunologia , Vacinação
17.
mBio ; 11(3)2020 06 19.
Artigo em Inglês | MEDLINE | ID: mdl-32561657

RESUMO

We propose the concept that administration of an unrelated live attenuated vaccine, such as MMR (measles, mumps, rubella), could serve as a preventive measure against the worst sequelae of coronavirus disease 2019 (COVID-19). There is mounting evidence that live attenuated vaccines provide nonspecific protection against lethal infections unrelated to the target pathogen of the vaccine by inducing "trained" nonspecific innate immune cells for improved host responses against subsequent infections. Mortality in COVID-19 cases is strongly associated with progressive lung inflammation and eventual sepsis. Vaccination with MMR in immunocompetent individuals has no contraindications and may be especially effective for health care workers who can easily be exposed to COVID-19. Following the lead of other countries conducting clinical trials with the live attenuated Mycobacterium bovis BCG (BCG) vaccine under a similar concept, a clinical trial with MMR in high-risk populations may provide a "low-risk-high-reward" preventive measure in saving lives during this unprecedented COVID-19 pandemic.


Assuntos
Vacina BCG/imunologia , Betacoronavirus/imunologia , Infecções por Coronavirus/prevenção & controle , Proteção Cruzada/imunologia , Vacina contra Sarampo-Caxumba-Rubéola/imunologia , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Vacinas Atenuadas/imunologia , Ensaios Clínicos como Assunto , Infecções por Coronavirus/patologia , Humanos , Sarampo/imunologia , Caxumba/imunologia , Mycobacterium bovis/imunologia , Pneumonia Viral/patologia , Rubéola (Sarampo Alemão)/imunologia , Vacinação
18.
Vet Res Commun ; 44(3-4): 131-136, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32583301

RESUMO

Post-mortem surveillance in Ireland discloses skin-test negative cattle with presumptive evidence of infection of Mycobacterium bovis (lesions at routine slaughter (LRS)), the causative agent of bovine tuberculosis (bTB). Laboratory confirmation of lesions has impacts on trade restrictions for herds, therefore if laboratory capacity was diminished, how herds are treated would require an informed risk policy. Here we report the proportion of herds with subsequent evidence of within-herd transmission, based on skin-test results. We assess how herd-size, herd-type, and bTB-history affect the probability of additional reactors at follow-up test using univariable and multivariable random-effects models. The study represents a rapid response to developing an evidential base for policy demands during an extraordinary event, the COVID-19 epidemic in Ireland. A dataset from 2005 to 2019 of breakdowns were collated. Overall, 20,116 breakdowns were initiated by LRS cases. During the index tests of these breakdowns, 3931 revealed ≥1 skin-test reactor animals (19.54%; ≥1 standard reactors: 3827; 19.02%). Increasing herd-size was associated with reactor disclosure on follow-up. For small herds (<33 animals), 11.74% of follow-up tests disclosed ≥1 reactor; 24.63% of follow-up tests from very large herds (>137) disclosed ≥1 reactors. Beef (13.87%) and "other" (13%) herd production types had lower proportion of index tests with reactors in comparison with dairy (28.27%) or suckler (20.48%) herds. Historic breakdown size during the previous 3-years was associated reactor disclosure risk on follow-up. Our results are useful for rapid tailored policy development aimed at identifying higher risk herds.


Assuntos
Tuberculose Bovina/epidemiologia , Matadouros , Animais , Bovinos , Irlanda/epidemiologia , Mycobacterium bovis , Vigilância da População , Probabilidade , Testes Cutâneos/veterinária , Tuberculose Bovina/diagnóstico
19.
Acta Biomed ; 91(2): 207-213, 2020 05 11.
Artigo em Inglês | MEDLINE | ID: covidwho-320998

RESUMO

Since the beginning of the COVID-19 epidemic, a possible explanation for the high heterogeneity of infection/mortality rates across involved countries was hinted in the prevalence of tuberculosis vaccination with Bacille Calmette-Guérin (BCG). A systematic review was therefore performed on May 2, 2020. A total of 13 articles were ultimately retrieved, 12 of them as preprint papers. All articles were ecological studies of low quality. Most of them did not include main confounding factors (i.e. demographic of the assessed countries, share of peo- ple residing in urban settings, etc.), and simply assessed the differences among incidence/mortality of COVID-19 with vaccination rates or by having vs. having not any vaccination policy for BCG. Even though all studies shared the very same information sources (i.e. international registries for BCG vaccination rates and open source data for COVID-19 epidemics), results were conflicting, with later studies apparently denying any true correlation between COVID-19 occurrence and BCG vaccination rates and/or policies. As a consequence, there is no sound evidence to recommend BCG vaccination for the prevention of COVID-19.


Assuntos
Vacina BCG/imunologia , Betacoronavirus , Infecções por Coronavirus/prevenção & controle , Mycobacterium bovis/imunologia , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Infecções por Coronavirus/imunologia , Humanos , Pneumonia Viral/imunologia , Tuberculose/imunologia , Tuberculose/prevenção & controle
20.
Mem Inst Oswaldo Cruz ; 115: e190401, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32401897

RESUMO

Bacillus Calmette Guerin (BCG) vaccines comprise a family of related strains. Whole genome sequencing has allowed the better characterisation of the differences between many of the BCG vaccines. As sequencing technologies improve, updating of publicly available sequence data becomes common practice. We hereby announce the draft genome of four commonly used BCG vaccines in Brazil, Argentina and Venezuela.


Assuntos
Vacina BCG/genética , Mapeamento Cromossômico , Mycobacterium bovis/genética , Argentina , Sequência de Bases , Brasil , Humanos , Dados de Sequência Molecular , Polimorfismo de Nucleotídeo Único , Venezuela
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