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Advances in the development of new vaccines for tuberculosis and Brazil’s role in the effort forward the end TB strategy Brazils Brazil s
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Junqueira-Kipnis, Ana Paula

; Leite, Luciana Cesar de Cerqueira

; Croda, Júlio

; Chimara, Erica

; Carvalho, Anna Cristina C

; Arcêncio, Ricardo Alexandre

Memórias do Instituto Oswaldo Cruz

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2024, Volume 119 elocation e240093

Abstract: En | Text: En | PDF: En

Tuberculosis (TB) continues to be the world’s leading killer of infectious diseases. Despite global efforts to gradually reduce the number of annual deaths and the incidence of this disease, the coronavirus disease 19 (COVID-19) pandemic caused decreased in TB detection and affected the prompt treatment TB which led to a setback to the 2019 rates. However, the development and testing of new TB vaccines has not stopped and now presents the possibility of implanting in the next five years a new vaccine that is affordable and might be used in the various key vulnerable populations affected by TB. Then, this assay aimed to discuss the main vaccines developed against TB that shortly could be selected and used worldwide, and additionally, evidence the Brazilian potential candidates’ vaccines in developing in Brazil that could be considered among those in level advanced to TB end. (TB worlds world s diseases 1 COVID19 COVID (COVID-19 201 rates However Then worldwide additionally candidates end COVID1 (COVID-1 20 (COVID- 2 (COVID

https://doi.org/10.1590/0074-02760240093

Non-tuberculous mycobacterial lung disease: a brief review focusing on radiological findings
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Anjos, Laura Raniere Borges dos

; Parreira, Poliana Lopes

; Torres, Pedro Paulo Teixeira Silva

; Kipnis, André

; Junqueira-Kipnis, Ana Paula

; Rabahi, Marcelo Fouad

Revista da Sociedade Brasileira de Medicina Tropical

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2020, Volume 53 elocation e20200241

Abstract: En | Text: En | PDF: En

Abstract The incidence and prevalence of lung disease caused by non-tuberculous mycobacteria (NTM-LD) has increased worldwide and its diagnosis represents a complex challenge. This article aims to review the tomographic findings of NTM-LD in order to facilitate their definitive diagnosis. The search for publications on the subject was performed in PMC and Scielo using the keywords ‘non-tuberculous mycobacteria’, ‘lung disease and computed tomography (CT)’ and ‘radiological findings’. The radiological findings described by 18 articles on mycobacteriosis were reviewed. In addition, CT images of patients diagnosed with NTM-LD were considered to represent radiological findings. Eighteen publications were used whose main findings were pulmonary cavitation (88.9%), bronchiectasis (77.8%), and pulmonary nodules (55.6%). Despite the overlaps in imaging-related analysis of myocobacterioses with other pulmonary infections, such as tuberculosis, the predominant involvement of the middle lobe and lingula should raise suspicion for NTM-LD.

https://doi.org/10.1590/0037-8682-0241-2020 1190 downloads

SOROEPIDEMIOLOGIA DE Neospora caninum E Toxoplasma gondii EM BOVINOS DA RAÇA CURRALEIRO
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Santin, Ana Paula Iglesias

; Juliano, Raquel Soares

; Silva, Andréa Caetano

; Oliveira, Vanessa Silvestre Ferreira de

; Junqueira-Kipnis, Ana Paula

; Brito, Wilia Marta Elsner Diederichsen de

; Fioravanti, Maria Clorinda Soares

Ciência Animal Brasileira

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2017, Volume 18 elocation e44649

Abstract: Pt En | Text: Pt En | PDF: Pt | PDF: En

Resumo Este estudo comparou a soroprevalência de N. caninum e T. gondii em bovinos Curraleiros ao de outras raças bovinas (Nelore, Girolando, Guzerá e Caracu). Foram utilizadas 119 fêmeas bovinas adultas provenientes de quatro propriedades localizadas nos estados de Goiás e Tocantins e na divisa entre Goiás, Minas Gerais e Bahia. Animais soropositivos para N. caninum foram encontrados em todas as propriedades e o número de Curraleiros reagentes foi significativamente maior em relação aos bovinos Guzerá e Nelore. Também foram identificados anticorpos anti-T. gondii nos animais em todas as propriedades. A prevalência de soropositivos para T. gondii foi semelhante entre Curraleiros e bovinos das raças Nelore, Girolando e Guzerá; entretanto, foi significativamente maior em relação à raça Caracu.

Abstract This study compared the health status of Curraleiro cattle and other breeds (Nellore, Girolando, Guzera, and Caracu) for toxoplasmosis and neosporosis screening against anti-Neospora caninum and anti-Toxoplasma gondii antibodies, respectively. We used 119 female bovines of Curraleiro, Guzera, Nellore, Caracu, and Girolando breeds from four farms in Goias and Tocantins states and in the border of Goias, Minas Gerais, and Bahia states. All the farms had seropositive bovines for N. caninum. The number of seropositive Curraleiro cattle was significantly higher than the number of Guzera and Nellore cattle. Also, antibodies against toxoplasmosis were found in animals from all properties. There was no significant difference between the number of seropositive Curraleiro cattle and the breeds Nellore, Girolando, and Guzerá; however, it was significantly higher than the number of seropositive animals of Caracu breed.

https://doi.org/10.1590/1089-6891v18e-44649 1325 downloads

The mc2-CMX vaccine induces an enhanced immune response against Mycobacterium tuberculosis compared to Bacillus Calmette-Guérin but with similar lung inflammatory effects
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Oliveira, Fábio Muniz de

; Trentini, Monalisa Martins

; Junqueira-Kipnis, Ana Paula

; Kipnis, André

Memórias do Instituto Oswaldo Cruz

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apr 2016, Volume 111 N. 4 Pages 223 - 231

Abstract: En | Text: En | PDF: En

Although the attenuated Mycobacterium bovis Bacillus Calmette-Guérin (BCG) vaccine has been used since 1921, tuberculosis (TB) control still proceeds at a slow pace. The main reason is the variable efficacy of BCG protection against TB among adults, which ranges from 0-80%. Subsequently, the mc2-CMX vaccine was developed with promising results. Nonetheless, this recombinant vaccine needs to be compared to the standard BCG vaccine. The objective of this study was to evaluate the immune response induced by mc2-CMX and compare it to the response generated by BCG. BALB/c mice were immunised with both vaccines and challenged withMycobacterium tuberculosis (Mtb). The immune and inflammatory responses were evaluated by ELISA, flow cytometry, and histopathology. Mice vaccinated with mc2-CMX and challenged with Mtb induced an increase in the IgG1 and IgG2 levels against CMX as well as recalled specific CD4+ T-cells that produced T-helper 1 cytokines in the lungs and spleen compared with BCG vaccinated and challenged mice. Both vaccines reduced the lung inflammatory pathology induced by the Mtb infection. The mc2-CMX vaccine induces a humoral and cellular response that is superior to BCG and is efficiently recalled after challenge with Mtb, although both vaccines induced similar inflammatory reductions.

https://doi.org/10.1590/0074-02760150411 1496 downloads

Brazilian Response to Global End TB Strategy : The National Tuberculosis Research Agenda
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Kritski, Afranio

; Barreira, Draurio

; Junqueira-Kipnis, Ana Paula

; Moraes, Milton Ozorio

; Campos, Maria Martha

; Degrave, Wim Mauritz

; Miranda, Silvana Spindola

; Krieger, Marco Aurelio

; Chimara, Erica

; Morel, Carlos

; Dalcolmo, Margareth Pretti

; Maciel, Ethel Leonor Noia

; Evangelista, Maria do Socorro Nantua

; Villa, Teresa Scatena

; Sanchez, Mauro

; Costa, Fernanda Dockhorn

; Queiroz, Inacio

; Oliveira, Martha Maria

; Souza Junior, Ruy

; Silva, Jose Roberto Lapa e

; Ruffino-Netto, Antonio

Revista da Sociedade Brasileira de Medicina Tropical

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feb 2016, Volume 49 N. 1 Pages 135 - 145

Abstract: En | Text: En | PDF: En

https://doi.org/10.1590/0037-8682-0330-2015 3881 downloads

The use of Mycobacterium tuberculosis HspX and GlcB proteins to identify latent tuberculosis in rheumatoid arthritis patients
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Silva, Bruna Daniella Souza

; Tannus-Silva, Daniela Graner Schuwartz

; Rabahi, Marcelo Fouad

; Kipnis, Andre

; Junqueira-Kipnis, Ana Paula

Memórias do Instituto Oswaldo Cruz

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feb 2014, Volume 109 N. 1 Pages 29 - 37

Abstract: En | Text: En | PDF: En

Rheumatoid arthritis (RA) is an autoimmune disease characterised by the destruction of articular cartilage and bone damage. The chronic treatment of RA patients causes a higher susceptibility to infectious diseases such as tuberculosis (TB); one-third of the world’s population is latently infected (LTBI) with Mycobacterium tuberculosis(Mtb). The tuberculin skin test is used to identify individuals LTBI, but many studies have shown that this test is not suitable for RA patients. The goal of this work was to test the specific cellular immune responses to the Mtb malate synthase (GlcB) and heat shock protein X (HspX) antigens of RA patients and to correlate those responses with LTBI status. The T-helper (Th)1, Th17 and Treg-specific immune responses to the GlcB and HspX Mtb antigens were analysed in RA patients candidates for tumour necrosis factor-α blocker treatment. Our results demonstrated that LTBI RA patients had Th1-specific immune responses to GlcB and HspX. Patients were followed up over two years and 14.3% developed active TB. After the development of active TB, RA patients had increased numbers of Th17 and Treg cells, similar to TB patients. These results demonstrate that a GlcB and HspX antigen assay can be used as a diagnostic test to identify LTBI RA patients.

https://doi.org/10.1590/0074-02760140140 2320 downloads

Cellular immune response of Curraleiro Pé-duro and Nellore calves following Mycobacterium bovis-BCG vaccination
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Maggioli, Mayara Fernanda

; Lobo, Joyce Rodrigues

; Fioravanti, Maria Clorinda Soares

; Kipnis, André

; Junqueira-Kipnis, Ana Paula

Pesquisa Veterinária Brasileira

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dec 2013, Volume 33 N. 12 Pages 1403 - 1408

Abstract: Pt En | Text: Pt En | PDF: Pt | PDF: En

O presente estudo teve como objetivo avaliar níveis sanguíneos de células CD4, CD8 e γδ no sangue periférico de bezerros Curraleiro Pé-Duro, bem como a produção específica de IFN-γ por essas células em resposta à vacinação com BCG, através de citometria de fluxo. A resposta imune específica contra BCG também foi avaliada por teste tuberculínico, realizado antes e 45 dias após a vacinação. Para fins de comparação, os mesmos parâmetros foram investigados em bezerros da raça Nelore, uma raça bovina exótica com resistência demonstrado anteriormente. Naturalmente, animais da raça Curraleiro Pé-Duro apresentaram maiores níveis de CD4, CD8 e linfócitos γδ. Em resposta a vacina, Curraleiro Pé-duro mostrou maior capacidade de responder especificamente ao BCG, gerando perfil de resistência (Th1), evidenciado pelo maior número de células CD4+ específicas produtoras de IFN-γ e maior reação cutânea a por tuberculina. Os maiores níveis basais de linfócitos, maior produção de IFN-γ e reação cutânea à prova tuberculínica provavelmente desempenham um papel positivo na proteção/resistência ao Mycobacterium tuberculosis.

The present study aimed to assess the CD4, CD8 and γδ blood levels for Curraleiro Pé-duro, as well as the specific IFN-γ response after BCG vaccination using flow cytometry. The specific immune response against BCG was also evaluated by tuberculin skin test, performed before and 45 days after the vaccination. For comparison purposes, the same parameters were investigated on Nellore calves, an exotic bovine with resistance previously demonstrated. Naturally, Curraleiro Pé-duro animals had greater levels of CD4, CD8 and γδ lymphocytes (p<0.05). In response to vaccine, Curraleiro Pé-duro showed greater ability to respond specifically to BCG, generating resistance profile (Th1), evidenced by greater number of antigen specific CD4+ cells producing IFN-γ (p<0.05) and also higher tuberculin skin test reaction (p<0.05). Additionally, vaccinated Curraleiro Pé-duro calves had higher CD4 cells numbers than both Nellore control (p<0.05) and vaccinated groups (p<0.05). Curraleiro Pé-duro calves' higher basal lymphocytes blood level and stronger response in both IFN-γ and tuberculin skin test parameters probably play a positive role on protection/resistance to Mycobacterium bovis.

2237 downloads

Role of antibodies reactive to HspX in discriminating pulmonary tuberculosis contacts with high risk of developing active disease
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Reis, Michelle Cristina Guerreiro dos

; Silva, Bruna Daniella de Souza

; Sousa, Eduardo Martins de

; Junqueira-Kipnis, Ana Paula

Brazilian Journal of Infectious Diseases

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dec 2011, Volume 15 N. 6 Pages 617 - 618

Abstract: En | Text: En | PDF: En

1654 downloads

Clinical data and molecular analysis of Mycobacterium tuberculosis isolates from drug-resistant tuberculosis patients in Goiás, Brazil
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Alves, Sueli Lemes de Ávila

; Metzker, Fabiana Sarcinelli

; Araújo-Filho, João Alves de

; Junqueira-Kipnis, Ana Paula

; Kipnis, André

Memórias do Instituto Oswaldo Cruz

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sep 2011, Volume 106 N. 6 Pages 655 - 661

Abstract: En | Text: En | PDF: En

Drug resistance is one of the major concerns regarding tuberculosis (TB) infection worldwide because it hampers control of the disease. Understanding the underlying mechanisms responsible for drug resistance development is of the highest importance. To investigate clinical data from drug-resistant TB patients at the Tropical Diseases Hospital, Goiás (GO), Brazil and to evaluate the molecular basis of rifampin (R) and isoniazid (H) resistance in Mycobacterium tuberculosis. Drug susceptibility testing was performed on 124 isolates from 100 patients and 24 isolates displayed resistance to R and/or H. Molecular analysis of drug resistance was performed by partial sequencing of the rpoB and katGgenes and analysis of the inhA promoter region. Similarity analysis of isolates was performed by 15 loci mycobacterial interspersed repetitive unit-variable number tandem repeat (MIRU-VNTR) typing. The molecular basis of drug resistance among the 24 isolates from 16 patients was confirmed in 18 isolates. Different susceptibility profiles among the isolates from the same individual were observed in five patients; using MIRU-VNTR, we have shown that those isolates were not genetically identical, with differences in one to three loci within the 15 analysed loci. Drug-resistant TB in GO is caused by M. tuberculosis strains with mutations in previously described sites of known genes and some patients harbour a mixed phenotype infection as a consequence of a single infective event; however, further and broader investigations are needed to support our findings.

3885 downloads

10.

Pesquisa de IgA contra o antígeno recombinante HspX de Mycobacterium tuberculosis no diagnóstico de tuberculose pleural
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Limongi, Loanda Carvalho Sant' Ana

; Olival, Liliane

; Conde, Marcus Barreto

; Junqueira-Kipnis, Ana Paula

Jornal Brasileiro de Pneumologia

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jun 2011, Volume 37 N. 3 Pages 302 - 307

Abstract: Pt En | Text: Pt En | PDF: Pt | PDF: En

OBJETIVO: Avaliar a acurácia da dosagem de IgA contra o antígeno recombinante HspX no líquido pleural e no soro de pacientes com derrame pleural para o diagnóstico de tuberculose pleural. MÉTODOS: Estudo transversal de teste diagnóstico. Amostras de líquido pleural e de soro de pacientes com derrame pleural e suspeita de tuberculose pleural foram avaliadas para a determinação da densidade óptica de IgA contra HspX utilizando ELISA indireto. RESULTADOS: Foram avaliadas amostras de líquido pleural e de soro de 132 pacientes: 97 com tuberculose pleural (grupo de estudo) e 35 com derrame pleural por outras causas (grupo controle). A dosagem de IgA em líquido pleural foi capaz de discriminar os pacientes com tuberculose pleural dos controles. A sensibilidade do teste em líquido pleural e em soro foi, respectivamente, de 69% e 30%, enquanto a especificidade foi de 83% e 84%, respectivamente. CONCLUSÕES: Os dados sugerem o potencial da utilização deste teste no diagnóstico de tuberculose pleural. Estudos com amostras maiores e em diferentes cenários epidemiológicos são necessários

OBJECTIVE: To evaluate the accuracy of determining specific IgA to HspX recombinant antigen in pleural fluid and serum samples for the diagnosis of pleural tuberculosis in patients with pleural effusion. METHODS: This was a cross-sectional study. Serum and pleural fluid samples of patients with pleural effusion and suspected of having pleural tuberculosis were tested with indirect ELISA in order to determine the optical density of specific IgA to HspX. RESULTS: We evaluated serum and pleural fluid samples from 132 patients: 97 diagnosed with pleural tuberculosis (study group) and 35 diagnosed with pleural effusion due to other causes (control group). The determination of IgA in pleural fluid satisfactorily discriminated between pleural tuberculosis patients and control patients. The sensitivity of the test in pleural fluid and in serum was 69% and 30%, respectively, whereas the specificity was 83% and 84%, respectively. CONCLUSIONS: Our data suggest that this test can be used in the diagnosis of pleural tuberculosis. Further studies, involving larger patient samples and different epidemiological scenarios, are warranted

3196 downloads

11.

Tuberculose em pacientes com artrite reumatoide: a dificuldade no diagnóstico da forma latente
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Silva, Daniela Graner Schuwartz Tannus

; Silva, Bruna Daniella de Souza

; Junqueira-Kipnis, Ana Paula

; Rabahi, Marcelo Fouad

Jornal Brasileiro de Pneumologia

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apr 2010, Volume 36 N. 2 Pages 243 - 251

Abstract: Pt En | Text: Pt En | PDF: Pt | PDF: En

Desde o início do uso de drogas anti-TNF para o tratamento da artrite reumatoide e outras doenças inflamatórias, casos de tuberculose pulmonar e extrapulmonar vêm sendo notificados em pacientes submetidos a tal tratamento. Na maioria das vezes, a doença se desenvolve durante as seis primeiras infusões. Todo paciente deve ser avaliado para tuberculose latente antes do início do uso de um bloqueador de TNF; no entanto, o diagnóstico de tuberculose latente é um desafio. A prova tuberculínica, o único teste disponível para a detecção de tuberculose latente por quase um século, apresenta uma série de limitações. Testes baseados na detecção da produção de IFN-γ in vitro por células mononucleares ativadas por antígenos específicos parecem ser mais acurados e vêm sendo pesquisados em pacientes com artrite reumatoide.

Since the beginning of the use of anti-TNF in the treatment of rheumatoid arthritis and other inflammatory diseases, cases of pulmonary tuberculosis and extrapulmonary tuberculosis have been reported in patients receiving such treatment. In most cases, the disease develops by the time the patient has received the sixth infusion. Every patient should be evaluated for latent tuberculosis infection prior to the use of a TNF inhibitor. However, the diagnosis of latent tuberculosis infection is a challenge. The tuberculin test, which was the only test available to detect latent tuberculosis infection for nearly a century, presents a number of limitations. Tests based on the detection of the in-vitro production of IFN-γ by mononuclear cells activated by specific antigens appear to be more accurate and have been studied in patients with rheumatoid arthritis.

19394 downloads

12.

Health care workers humoral immune response against GLcB, MPT51 and HSPX from Mycobacterium tuberculosis
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Reis, Michelle Cristina Guerreiro dos

; Rabahi, Marcelo Fouad

; Kipnis, André

; Junqueira-Kipnis, Ana Paula

Brazilian Journal of Infectious Diseases

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dec 2009, Volume 13 N. 6 Pages 417 - 421

Abstract: En | Text: En | PDF: En

Tuberculosis (TB) is one of the oldest human infectious diseases and one third of the world's population is latently infected. Brazil is an endemic area for TB. One of the most important challenges in TB control is the identification of latently infected individuals. Health Care Workers (HCW) are at high risk of being infected with Mycobacterium tuberculosis and even to become TB latently infected. The aim of this study was to increase knowledge about humoral immune response in TB latently infected individuals. HCW were classified according to their tuberculin skin test (TST), as positive or negative. The antibody response to GLcB, MPT51 and HSPX from Mycobacterium tuberculosis was evaluated. TST negative HCW constituted the majority of those who showed a humoral immune response. Antibody levels varied according to antigen characteristics, TST and BCG status. We suggest that possibly the presence of those antibodies could have a function in the protective immune response against Mycobacterium tuberculosis.

2049 downloads

13.

Extensively drug-resistant tuberculosis: a case report and literature review
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Araújo-Filho, João Alves de

; Vasconcelos-Jr, Arioldo Carvalho

; Sousa, Eduardo Martins de

; Silveira, Colombina da

; Ribeiro, Elisangela

; Kipnis, André

; Junqueira-Kipnis, Ana Paula

Brazilian Journal of Infectious Diseases

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oct 2008, Volume 12 N. 5 Pages 447 - 452

Abstract: En | Text: En | PDF: En

Extensively drug-resistant tuberculosis (XDR-TB) is an emerging health problem that threatens tuberculosis (TB) control worldwide, since suitable treatment for this disease has not yet been found. We report a case of secondary pulmonary XDR-TB in a 54-year-old, HIV-negative male from Goiânia, Brazil. The patient had long-standing pulmonary tuberculosis (nine years) with extensive bilateral lung damage and had been treated with multiple antituberculosis drugs (self-administered) before XDR-TB diagnosis. The strain of Mycobacterium tuberculosis was resistant to R- rifampicin, H-isoniazid, E-ethambutol, Eto-ethionamide, Ofx-ofloxacin, and Am-amikacin. This patient died with multiple organ failure due to sepsis secondary to bacterial pneumonia.

4786 downloads

14.

Multidrug-resistant tuberculosis: case reports study in a central state of Brazil
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Araújo-Filho, João Alves de

; Vasconcelos-Jr, Arioldo Carvalho

; Sousa, Eduardo Martins de

; Silveira, Colombina da

; Sousa, Patrícia Tavares Pereira de

; Severo, Klaus Andrade

; Vieira, Ludmila Ferreira

; Kipnis, André

; Junqueira-Kipnis, Ana Paula

Brazilian Journal of Infectious Diseases

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feb 2008, Volume 12 N. 1 Pages 94 - 98

Abstract: En | Text: En | PDF: En

Multidrug-resistant tuberculosis (MDR-TB) is an emerging and worrisome health problem that threatens tuberculosis (TB) control worldwide. The clinical management of MDR-TB is a complex issue associated with the use of multiple drugs for a long period, usually accompanied by side effects and high costs. The objective of this work was to relate cases of MDR-TB occurring in Goiás, a central state of Brazil. We related five cases of MDR-TB, three women and two men. All were pulmonary cases. Three were in their second treatment and two in their first treatment. Surgical pulmonary resection was performed in one case. One death occurred. Lack of adherence, gastric intolerance to anti-TB drugs and poor clinical management were the main aspects related to the emergent resistance. A revision of the main clinical aspects of this disease was performed.

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