Standard culture-based testing of the susceptibility of Mycobacterium tuberculosis to pyrazinamid... more Standard culture-based testing of the susceptibility of Mycobacterium tuberculosis to pyrazinamide is difficult to perform. This systematic review with meta-analyses evaluated the roles of molecular assays targeting pncA and of pyrazinamidase assays. PubMed and Embase were searched for relevant publications in English. Sensitivity and specificity were estimated in bivariate random-effects models. Of 128 articles identified, 73 sets of data involving culture isolates were initially included in meta-analyses. Summary estimates of sensitivity and specificity, respectively, were 87% and 93% for PCR-DNA sequencing ( n = 29), 75% and 95% for PCR-single-stranded conformation polymorphism (SSCP) ( n = 5), 96% and 97% for a mixture of other molecular assays ( n = 6), and 89% and 97% for pyrazinamidase assays using the Wayne method ( n = 33). The median prevalence (range) of pyrazinamide resistance was 51% (31% to 89%) in multidrug-resistant M. tuberculosis isolates and 5% (0% to 9%) in non-m...
12º Congresso Internacional da Rede Unida, Mar 21, 2016
O Estreptococo do Grupo B (EGB) ou Streptococcus agalactiae pode fazer parte da microbiota dos se... more O Estreptococo do Grupo B (EGB) ou Streptococcus agalactiae pode fazer parte da microbiota dos seres humanos, colonizando principalmente o trato gastro-intestinal e geniturinario. Esta especie e frequentemente relacionada a doencas potencialmente fatais em recem-nascidos, como septicemia, pneumonia e meningite e esta associada a complicacoes durante a gravidez e periodo pos-parto. Os objetivos deste estudo foram analisar a ocorrencia de EGB em gestantes usuarias do servico publico de saude, o desempenho do meio de cultura Hitchens-Pike-Todd-Hewitt (HPTH) e a sensibilidade antimicrobiana de isolados clinicos de EGB. Estudo transversal analitico descritivo realizado com 556 gestantes, das quais 496 estavam com 35-37 semanas de gestacao e 60 estavam com ≥ 38 semanas. O estudo foi realizado de setembro de 2011 a marco de 2014 no norte do Parana. Amostras clinicas – vaginal e anorretal – de cada gestante foram semeadas em agar sangue de carneiro, em meio HPTH e Todd-Hewitt. Os isolados clinicos estudados foram submetidos ao teste de susceptibilidade aos antimicrobianos por difusao em agar, de acordo com as normas do Clinical and Laboratory Standards Institute (CLSI). Das 496 gestantes, 141 (28,4%) foram positivas para EGB, com base na combinacao dos tres meios de cultura e especimes clinicos. As taxas de deteccao foram de 22,2% para o meio HPTH, 21,2% para agar sangue de carneiro, e 13,1% para o caldo de enriquecimento Todd-Hewitt. Das 60 gestantes com ≥ 38 semanas de gestacao, sete (11,7%) foram positivas para EGB, sendo que houve crescimento nos meios de HPTH e Agar sangue de carneiro. Das 141 gestantes positivas para EGB foram realizados 136 testes de sensibilidade aos antimicrobianos, no qual 100% foram sensiveis a penicilina. A eritromicina apresentou 8,1% de resistencia e a clindamicina 2,2%. Os resultados demonstram que o meio HPTH e Agar sangue de carneiro foram mais sensiveis que o caldo de enriquecimento Todd-Hewitt para triagem de EGB em gestantes, indicando que os dois meios devem ser usados em conjunto para amostras vaginal e anorretal. Todos os isolados de EGB mostraram sensibilidade a droga mais frequentemente usada para a profilaxia intraparto: penicilina. O indice de resistencia a clindamicina e a eritromicina, embora baixo, tambem foi detectado. Isto mostra a importância de se avaliar a susceptibilidade aos antimicrobianos evitando possiveis falhas na quimioprofilaxia empirica, e assim prevenir corretamente a infeccao neonatal. A prevalencia de colonizacao por EGB nas gestantes deste estudo confirma a necessidade de inserir a pesquisa desta bacteria como rotina no protocolo de exames pre-natais preconizados pelo SUS, para assim realizar o diagnostico e tratamento previo, minimizando custos com internacao hospitalar e melhorias na qualidade da saude das gestantes e recem-nascidos.
Chronic infections caused by M. abscessus are an emerging challenge in public health, posing a su... more Chronic infections caused by M. abscessus are an emerging challenge in public health, posing a substantial health and economic burden, especially in patients with cystic fibrosis. Treatment of M. abscessus infections with antibiotics is particularly challenging, as its complex drug resistance mechanisms, including constitutive resistance through DNA mutation, lead to high rates of treatment failure.
This work describes a case of Haemophilus influenzae serotype a meningitis in Brazil, after almos... more This work describes a case of Haemophilus influenzae serotype a meningitis in Brazil, after almost a decade since the introduction of Haemophilus influenzae serotype b conjugate vaccine. Uncertainty about the replacement of H. influenzae serotypes as a cause of invasive diseases justifies continuous surveillance, coupled with investigations of carriage rates and requirements of chemoprophylaxis in contact persons.
Segundo a Organizacao Mundial de Saude, a tuberculose (TB) mata aproximadamente dois milhoes de p... more Segundo a Organizacao Mundial de Saude, a tuberculose (TB) mata aproximadamente dois milhoes de pessoas a cada ano. Dessa forma, o objetivo deste trabalho foi avaliar o perfil epidemiologico da TB na 15a Regional de Saude de Maringa-PR no periodo de 2005-2010. Para tanto, utilizou-se de um estudo transversal de 2005 a 2010 apos aprovacao pelo Comite de Etica em Pesquisa em Seres Humanos (SESA/HT). Participaram deste estudo, 3.516 pacientes que foram atendidos no Laboratorio de Ensino e Pesquisa em Analises Clinicas da Universidade Estadual de Maringa (LEPAC/UEM) no periodo de 2005-2010. O genero masculino foi o mais acometido pela TB (65%) em relacao ao feminino (35%). A idade media dos pacientes acometidos pela doenca foi de 45,03 anos, sendo que a maior taxa de incidencia ocorreu na faixa de 21 a 30 anos. As analises apontaram que houve um aumento no numero de casos positivos proporcionalmente ao numero de casos diagnosticados com suspeita de TB ao longo dos anos. A forma pulmonar (95,7%) independente do ano, genero e faixa etaria analisada foi a mais diagnosticada. Com estes dados, espera-se que este estudo possa nortear as politicas publicas de saude direcionadas as reais caracteristicas da localidade, com acoes de planejamento e controle da doenca, visando a promocao da saude da populacao. EPIDEMIOLOGICAL PROFILE OF TUBERCULOSIS IN THE 15 TH REGIONAL HEALTH MARINGA-PR, FROM 2005 TO 2010 ABSTRACT According to the World Health Organization, tuberculosis (TB) kills approximately two million people each year. Thus, the objective of this study was to evaluate the epidemiological profile of TB in the 15 th Regional Health Maringa-PR in the period 2005-2010. For this, we used a cross-sectional study from 2005 to 2010 after approval by the Ethics in Human Research (SESA / HT). Participated in this study, 3,516 patients were treated at the Laboratory of Teaching and Research in Clinical Analyses, State University of Maringa (LEPAC/ UEM) in the period 2005-2010. The male was the most affected by TB (65%) than female (35%). The average age of patients affected by the disease was 45.03 years, with highest incidence rate occurred in the range of 21 to 30 years. The analysis indicated that there was an increase in the number of positive cases in proportion to the number of diagnosed cases of suspected TB over the years. The pulmonary form (95.7%) regardless of year, gender and age was considered the most diagnosed. Thus, it is important that studies be conducted to determine the behavior and the epidemiology of the disease in different regions of the country. With these data, it is expected that this study will guide the public health policies directed to the real characteristics of the locality, with action planning and disease control for the promotion of population health.
Journal of Biomolecular Structure & Dynamics, Feb 23, 2022
The development of new drugs against Mycobacterium tuberculosis is an essential strategy for figh... more The development of new drugs against Mycobacterium tuberculosis is an essential strategy for fighting drug resistance. Although 3-dehydroquinate dehydratase (MtDHQ) is known to be a highly relevant target for M. tuberculosis, current research shows new putative inhibitors of MtDHQ selected by a large-scale ensemble-docking strategy combining ligand- and target-based chemoinformatic methods to deep learning. Initial chemical library was reduced from 216 million to approximately 460 thousand after pharmacophore, toxicity and molecular weight filters. Final library was subjected to an ensemble-docking protocol in GOLD which selected the top 300 molecules (GHITS). GHITS displayed different structures and characteristics when compared to known inhibitors (KINH). GHITS were further screened by post-docking analysis in AMMOS2 and deep learning virtual screening in DeepPurpose. DeepPurpose predicted that a number of GHITS had comparable or better affinity for the target than KINH. The best molecule was selected by consensus ranking using GOLD, AMMOS2 and DeepPurpose scores. Molecular dynamics revealed that the top hit displayed consistent and stable binding to MtDHQ, making strong interactions with active-site loop residues. Results forward new putative inhibitors of MtDHQ and reinforce the potential application of artificial intelligence methods for drug design. This work represents the first step in the validation of these molecules as inhibitors of MtDHQ.
Standard culture-based testing of the susceptibility of Mycobacterium tuberculosis to pyrazinamid... more Standard culture-based testing of the susceptibility of Mycobacterium tuberculosis to pyrazinamide is difficult to perform. This systematic review with meta-analyses evaluated the roles of molecular assays targeting pncA and of pyrazinamidase assays. PubMed and Embase were searched for relevant publications in English. Sensitivity and specificity were estimated in bivariate random-effects models. Of 128 articles identified, 73 sets of data involving culture isolates were initially included in meta-analyses. Summary estimates of sensitivity and specificity, respectively, were 87% and 93% for PCR-DNA sequencing ( n = 29), 75% and 95% for PCR-single-stranded conformation polymorphism (SSCP) ( n = 5), 96% and 97% for a mixture of other molecular assays ( n = 6), and 89% and 97% for pyrazinamidase assays using the Wayne method ( n = 33). The median prevalence (range) of pyrazinamide resistance was 51% (31% to 89%) in multidrug-resistant M. tuberculosis isolates and 5% (0% to 9%) in non-m...
12º Congresso Internacional da Rede Unida, Mar 21, 2016
O Estreptococo do Grupo B (EGB) ou Streptococcus agalactiae pode fazer parte da microbiota dos se... more O Estreptococo do Grupo B (EGB) ou Streptococcus agalactiae pode fazer parte da microbiota dos seres humanos, colonizando principalmente o trato gastro-intestinal e geniturinario. Esta especie e frequentemente relacionada a doencas potencialmente fatais em recem-nascidos, como septicemia, pneumonia e meningite e esta associada a complicacoes durante a gravidez e periodo pos-parto. Os objetivos deste estudo foram analisar a ocorrencia de EGB em gestantes usuarias do servico publico de saude, o desempenho do meio de cultura Hitchens-Pike-Todd-Hewitt (HPTH) e a sensibilidade antimicrobiana de isolados clinicos de EGB. Estudo transversal analitico descritivo realizado com 556 gestantes, das quais 496 estavam com 35-37 semanas de gestacao e 60 estavam com ≥ 38 semanas. O estudo foi realizado de setembro de 2011 a marco de 2014 no norte do Parana. Amostras clinicas – vaginal e anorretal – de cada gestante foram semeadas em agar sangue de carneiro, em meio HPTH e Todd-Hewitt. Os isolados clinicos estudados foram submetidos ao teste de susceptibilidade aos antimicrobianos por difusao em agar, de acordo com as normas do Clinical and Laboratory Standards Institute (CLSI). Das 496 gestantes, 141 (28,4%) foram positivas para EGB, com base na combinacao dos tres meios de cultura e especimes clinicos. As taxas de deteccao foram de 22,2% para o meio HPTH, 21,2% para agar sangue de carneiro, e 13,1% para o caldo de enriquecimento Todd-Hewitt. Das 60 gestantes com ≥ 38 semanas de gestacao, sete (11,7%) foram positivas para EGB, sendo que houve crescimento nos meios de HPTH e Agar sangue de carneiro. Das 141 gestantes positivas para EGB foram realizados 136 testes de sensibilidade aos antimicrobianos, no qual 100% foram sensiveis a penicilina. A eritromicina apresentou 8,1% de resistencia e a clindamicina 2,2%. Os resultados demonstram que o meio HPTH e Agar sangue de carneiro foram mais sensiveis que o caldo de enriquecimento Todd-Hewitt para triagem de EGB em gestantes, indicando que os dois meios devem ser usados em conjunto para amostras vaginal e anorretal. Todos os isolados de EGB mostraram sensibilidade a droga mais frequentemente usada para a profilaxia intraparto: penicilina. O indice de resistencia a clindamicina e a eritromicina, embora baixo, tambem foi detectado. Isto mostra a importância de se avaliar a susceptibilidade aos antimicrobianos evitando possiveis falhas na quimioprofilaxia empirica, e assim prevenir corretamente a infeccao neonatal. A prevalencia de colonizacao por EGB nas gestantes deste estudo confirma a necessidade de inserir a pesquisa desta bacteria como rotina no protocolo de exames pre-natais preconizados pelo SUS, para assim realizar o diagnostico e tratamento previo, minimizando custos com internacao hospitalar e melhorias na qualidade da saude das gestantes e recem-nascidos.
Chronic infections caused by M. abscessus are an emerging challenge in public health, posing a su... more Chronic infections caused by M. abscessus are an emerging challenge in public health, posing a substantial health and economic burden, especially in patients with cystic fibrosis. Treatment of M. abscessus infections with antibiotics is particularly challenging, as its complex drug resistance mechanisms, including constitutive resistance through DNA mutation, lead to high rates of treatment failure.
This work describes a case of Haemophilus influenzae serotype a meningitis in Brazil, after almos... more This work describes a case of Haemophilus influenzae serotype a meningitis in Brazil, after almost a decade since the introduction of Haemophilus influenzae serotype b conjugate vaccine. Uncertainty about the replacement of H. influenzae serotypes as a cause of invasive diseases justifies continuous surveillance, coupled with investigations of carriage rates and requirements of chemoprophylaxis in contact persons.
Segundo a Organizacao Mundial de Saude, a tuberculose (TB) mata aproximadamente dois milhoes de p... more Segundo a Organizacao Mundial de Saude, a tuberculose (TB) mata aproximadamente dois milhoes de pessoas a cada ano. Dessa forma, o objetivo deste trabalho foi avaliar o perfil epidemiologico da TB na 15a Regional de Saude de Maringa-PR no periodo de 2005-2010. Para tanto, utilizou-se de um estudo transversal de 2005 a 2010 apos aprovacao pelo Comite de Etica em Pesquisa em Seres Humanos (SESA/HT). Participaram deste estudo, 3.516 pacientes que foram atendidos no Laboratorio de Ensino e Pesquisa em Analises Clinicas da Universidade Estadual de Maringa (LEPAC/UEM) no periodo de 2005-2010. O genero masculino foi o mais acometido pela TB (65%) em relacao ao feminino (35%). A idade media dos pacientes acometidos pela doenca foi de 45,03 anos, sendo que a maior taxa de incidencia ocorreu na faixa de 21 a 30 anos. As analises apontaram que houve um aumento no numero de casos positivos proporcionalmente ao numero de casos diagnosticados com suspeita de TB ao longo dos anos. A forma pulmonar (95,7%) independente do ano, genero e faixa etaria analisada foi a mais diagnosticada. Com estes dados, espera-se que este estudo possa nortear as politicas publicas de saude direcionadas as reais caracteristicas da localidade, com acoes de planejamento e controle da doenca, visando a promocao da saude da populacao. EPIDEMIOLOGICAL PROFILE OF TUBERCULOSIS IN THE 15 TH REGIONAL HEALTH MARINGA-PR, FROM 2005 TO 2010 ABSTRACT According to the World Health Organization, tuberculosis (TB) kills approximately two million people each year. Thus, the objective of this study was to evaluate the epidemiological profile of TB in the 15 th Regional Health Maringa-PR in the period 2005-2010. For this, we used a cross-sectional study from 2005 to 2010 after approval by the Ethics in Human Research (SESA / HT). Participated in this study, 3,516 patients were treated at the Laboratory of Teaching and Research in Clinical Analyses, State University of Maringa (LEPAC/ UEM) in the period 2005-2010. The male was the most affected by TB (65%) than female (35%). The average age of patients affected by the disease was 45.03 years, with highest incidence rate occurred in the range of 21 to 30 years. The analysis indicated that there was an increase in the number of positive cases in proportion to the number of diagnosed cases of suspected TB over the years. The pulmonary form (95.7%) regardless of year, gender and age was considered the most diagnosed. Thus, it is important that studies be conducted to determine the behavior and the epidemiology of the disease in different regions of the country. With these data, it is expected that this study will guide the public health policies directed to the real characteristics of the locality, with action planning and disease control for the promotion of population health.
Journal of Biomolecular Structure & Dynamics, Feb 23, 2022
The development of new drugs against Mycobacterium tuberculosis is an essential strategy for figh... more The development of new drugs against Mycobacterium tuberculosis is an essential strategy for fighting drug resistance. Although 3-dehydroquinate dehydratase (MtDHQ) is known to be a highly relevant target for M. tuberculosis, current research shows new putative inhibitors of MtDHQ selected by a large-scale ensemble-docking strategy combining ligand- and target-based chemoinformatic methods to deep learning. Initial chemical library was reduced from 216 million to approximately 460 thousand after pharmacophore, toxicity and molecular weight filters. Final library was subjected to an ensemble-docking protocol in GOLD which selected the top 300 molecules (GHITS). GHITS displayed different structures and characteristics when compared to known inhibitors (KINH). GHITS were further screened by post-docking analysis in AMMOS2 and deep learning virtual screening in DeepPurpose. DeepPurpose predicted that a number of GHITS had comparable or better affinity for the target than KINH. The best molecule was selected by consensus ranking using GOLD, AMMOS2 and DeepPurpose scores. Molecular dynamics revealed that the top hit displayed consistent and stable binding to MtDHQ, making strong interactions with active-site loop residues. Results forward new putative inhibitors of MtDHQ and reinforce the potential application of artificial intelligence methods for drug design. This work represents the first step in the validation of these molecules as inhibitors of MtDHQ.
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Papers by Rosilene Cardoso