Revista do Instituto de Medicina Tropical de São Paulo, 2021
Tuberculosis is a worldwide public health problem, which, even with available treatment, continue... more Tuberculosis is a worldwide public health problem, which, even with available treatment, continues to cause deaths worldwide. One of the obstacles to control the disease is the multifactorial difficulty of patients to adhere to treatment, in addition to the difficulty of health workers in circumventing barriers to implement strategies such as the directly observed treatment (DOT). The aim of this study is to analyze the performance and challenges faced by health workers in the use of DOT in tuberculosis. This is a descriptive, quali-quantitative study using data from interviews with primary-care professionals working in nine municipalities of Parana State, Brazil. The professionals answered a questionnaire containing four closed questions about DOT and an open question related to their professional opinion about the strategy. Quantitative data were entered into a spreadsheet and statistically propagated. Qualitative data were treated from the transcription of statements, subsequently submitted to content analysis. Of the 387 professionals interviewed, at least 58.9% had some knowledge about DOT. Among the main challenges faced by the professionals are: lack of user commitment to treatment (48.3%), users' difficulty in attending the basic health clinics (BHC) (31.4%), professionals' difficulty to reach the place where patients are treated (8.8 %), insufficient staff / lack of human resources (4.1%) and use of illicit drugs by patients (3.9%). Blaming the user and the lack of resources are the main highlights, in addition to issues such as the professionals' lack of access and knowledge that are highlighted by the difficulty of patients to adhere to the treatment of tuberculosis according to the participants' statements. The issues were raised by health workers manifestations involving adherence to treatment according to the DOT in the studied health region. It is possible, in this context, to observe the need for improvement in the knowledge of professionals with regard to the DOT, the importance of their bond with patients and families and the recognition of the part of responsibility that belongs to the health team on guaranteeing treatment.
The authors report a case of cutaneous tuberculosis in a 63-year-old female patient, who had an i... more The authors report a case of cutaneous tuberculosis in a 63-year-old female patient, who had an infiltrated, erythematous-ferruginous plaque of indurated aspect on her right leg and a nonreactive PPD skin test. Diagnosis was made by tissue culture and PCR of skin biopsy material. The treatment was performed with pyrazinamide, rifampicin, isoniazid and ethambutol, with good response.
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.
In this work the aim of study was the synthesis and evaluation of in vitro anti-Mycobacterium tub... more In this work the aim of study was the synthesis and evaluation of in vitro anti-Mycobacterium tuberculosis activity as well as the cytotoxicity in VERO cells of a series of 17 novel thiosemicarbazones derived from the natural monoterpene (-)-camphene by REMA and MTT methods. Overall, the majority of tested compounds exhibited considerable inhibitory effects on the growth of M. tuberculosis H 37 Rv, especially the derivatives 3, 4a-c, 4f, 4i, 4k, 5 and 6a-b. MIC values of 20 tested compounds ranged from 3.9 µg/mL to > 250 µg/mL. It was found that when inserting new nitrogenous groups to the (-)-camphene increased the anti-M. tuberculosis activity of some compounds. The SI was calculated for all compounds that showed highly potent anti-M. tuberculosis activity and the best SI values were 21.36, 26.92 and 31.62 (4b, 6a and 6b), and may be considered potential candidates for future antituberculosis drugs.
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.
O presente estudo objetivou avaliar o panorama epidemiológico da malária no estado do Amapá, deli... more O presente estudo objetivou avaliar o panorama epidemiológico da malária no estado do Amapá, delimitando o perfil de acometimento da doença e sua distribuição geográfica no estado, no período de janeiro de 2015 a dezembro de 2019. Trata-se de um estudo de caráter descritivo, e retrospectivo, a partir da coleta de dados no Sistema de Vigilância Epidemiológica (SIVEP-Malária), com posterior análise estatística descritiva, associativa e comparativa. Os resultados demonstram diminuição percentual e do Índice Parasitário Anual (IPA), das lâminas positivas para malária no estado, com os municípios de Serra do Navio, Calçoene, Mazagão e Pedra Branca do Amapari registrando os maiores valores médios de IPA. Evidenciou-se maior prevalência na faixa etária de 10 a 19 anos (24,8%), seguida pela faixa de 20 a 29 anos (21,5%); no sexo masculino (62,1%), em relação ao feminino (37,9%); nos indivíduos com menores níveis de escolaridade; e naqueles que desenvolvem atividades relacionadas à agricultura (46,44%) e à garimpagem (19,5%), quando desconsiderada a categoria "outras". A diminuição bruta e ajustada dos casos sugere possibilidade de controle da doença pela implementação de políticas de educação em saúde, conscientização para medidas preventivas, mecanismos para controle de vetores e estratégias de diagnóstico e tratamento precoces.
Revista Do Instituto De Medicina Tropical De Sao Paulo, Feb 15, 2018
The aim of this study was to determine the prevalence of GBS colonization in pregnant women in a ... more The aim of this study was to determine the prevalence of GBS colonization in pregnant women in a public health service. Methods: A study of 496 pregnant women at 35-37 gestational weeks was conducted from September 2011 to March 2014 in 21 municipalities of the 18 th Health Region of Paraná State. Vaginal and anorectal samples of each woman were plated on sheep blood agar, and in HPTH and Todd-Hewitt enrichment broths. Results: Of the 496 pregnant women, 141 (28.4%) were positive for GBS based on the combination of the three culture media with vaginal and anorectal samples. The prevalence was 23.7% for vaginal samples and 21.9% for anorectal ones. Among the variables analyzed in this study, only urinary infection was a significant factor (0.026) associated with GBS colonization in women. Conclusions: Based on these results, health units should performs universal screening of pregnant women and hospitals should provide adequate prophylaxis, when indicated.
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.
Essential oils from fresh Piperaceae leaves were obtained by hydrodistillation and analyzed by ga... more Essential oils from fresh Piperaceae leaves were obtained by hydrodistillation and analyzed by gas chromatography mass spectrometry (GC-MS), and a total of 68 components were identified. Principal components analysis results showed a chemical variability between species, with sesquiterpene compounds predominating in the majority of species analyzed. The composition of the essential oil of Piper mosenii was described for the first time. The cytotoxicity of the essential oils was evaluated in peritoneal macrophages and the oils of P. rivinoides, P. arboretum, and P. aduncum exhibited the highest values, with cytotoxic concentration at 50% (CC 50) > 200 µg/mL. Both P. diospyrifolium and P. aduncum displayed activity against Leishmania amazonensis, and were more selective for the parasite than for the macrophages, with a selectivity index (SI) of 2.35 and >5.52, respectively. These SI values were greater than the 1 for the standard drug pentamidine. The antileishmanial activity of the essential oils of P. diospyrifolium and P. aduncum was described for the first time. P. rivinoides, P. cernuum, and P. diospyrifolium displayed moderate activity against the Mycobacterium tuberculosis H 37 Rv bacillus, with a minimum inhibitory concentration (MIC) of 125 µg/mL. These results are relevant and suggests their potential for therapeutic purposes. Nevertheless, further studies are required to explain the exact mechanism of action of these essential oils.
se aumento de 68,64% da taxa de mortalidade geral, sendo que nos homens, esse aumento foi de 62,8... more se aumento de 68,64% da taxa de mortalidade geral, sendo que nos homens, esse aumento foi de 62,86%, e nas mulheres, de 92,65%. Quanto à causa de suicídio e à faixa etária, respectivamente, observou-se que a maioria ocorreu por lesão autoprovocada de forma intencional causada por enforcamento, estrangulamento e sufocação (X70), e o maior percentual de mortes foi entre 20 e 29 anos (35,05%), tanto no sexo masculino quanto no feminino. Conclusões: O suicídio é um problema complexo com grande impacto na saúde pública mundial e que vem apresentando crescimento nos últimos anos, como evidenciado neste estudo. Portanto, é salutar desenvolver análises epidemiológicas que auxiliem na identificação de grupos em risco de suicídio, a fim de compreender os aspectos envoltos nesse fenômeno, bem como seja possível adaptar intervenções para que haja maior eficácia e alcance na abordagem dessas populações.
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.
In developing nations, 10e20% of the human cases of tuberculosis are caused by Mycobacterium bovi... more In developing nations, 10e20% of the human cases of tuberculosis are caused by Mycobacterium bovis. However, this percentage may be underestimated because most laboratories in developing countries do not routinely perform mycobacterial cultures, and only a few have the systems in place to identify M. bovis. There are few studies investigating genotypic diversity and drug resistance in M. bovis from animal and/or human infections. The genotypic diversity of M. bovis strains obtained from bovine lymph nodes were investigated by spacer oligonucleotide typing (spoligotyping) and mycobacterial interspersed repetitive unitevariablenumber tandem repeat typing (MIRU-VNTR). The phenotypic resistance to isoniazid and rifampicin and MIC values of the isolates were determined using the resazurin microtiter assay plate method (REMA). The evaluation of the possible genetic basis for such resistance was performed with GenoType MTBDRplus. Sixty-seven isolates were obtained, of which 11 (16%) were MDR-TB, 8 (12%) were isoniazidresistant, and 2 (3%) were rifampicin-resistant. Mutations associated with drug resistance were not found. Genotyping techniques enabled the grouping of the strains into 12 clusters and 21 isolates with unique profiles. The high frequency of M. bovis reinforces the impact of the pathogen as a major causal agent of bovine tuberculosis in the study area. The resistance of the strains to drugs used for first-line treatment of human tuberculosis raises public health concerns. Further studies are required to elucidate the basis of drug resistance and genotypic diversity in M. bovis.
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.
Revista do Instituto de Medicina Tropical de São Paulo, 2021
Tuberculosis is a worldwide public health problem, which, even with available treatment, continue... more Tuberculosis is a worldwide public health problem, which, even with available treatment, continues to cause deaths worldwide. One of the obstacles to control the disease is the multifactorial difficulty of patients to adhere to treatment, in addition to the difficulty of health workers in circumventing barriers to implement strategies such as the directly observed treatment (DOT). The aim of this study is to analyze the performance and challenges faced by health workers in the use of DOT in tuberculosis. This is a descriptive, quali-quantitative study using data from interviews with primary-care professionals working in nine municipalities of Parana State, Brazil. The professionals answered a questionnaire containing four closed questions about DOT and an open question related to their professional opinion about the strategy. Quantitative data were entered into a spreadsheet and statistically propagated. Qualitative data were treated from the transcription of statements, subsequently submitted to content analysis. Of the 387 professionals interviewed, at least 58.9% had some knowledge about DOT. Among the main challenges faced by the professionals are: lack of user commitment to treatment (48.3%), users' difficulty in attending the basic health clinics (BHC) (31.4%), professionals' difficulty to reach the place where patients are treated (8.8 %), insufficient staff / lack of human resources (4.1%) and use of illicit drugs by patients (3.9%). Blaming the user and the lack of resources are the main highlights, in addition to issues such as the professionals' lack of access and knowledge that are highlighted by the difficulty of patients to adhere to the treatment of tuberculosis according to the participants' statements. The issues were raised by health workers manifestations involving adherence to treatment according to the DOT in the studied health region. It is possible, in this context, to observe the need for improvement in the knowledge of professionals with regard to the DOT, the importance of their bond with patients and families and the recognition of the part of responsibility that belongs to the health team on guaranteeing treatment.
The authors report a case of cutaneous tuberculosis in a 63-year-old female patient, who had an i... more The authors report a case of cutaneous tuberculosis in a 63-year-old female patient, who had an infiltrated, erythematous-ferruginous plaque of indurated aspect on her right leg and a nonreactive PPD skin test. Diagnosis was made by tissue culture and PCR of skin biopsy material. The treatment was performed with pyrazinamide, rifampicin, isoniazid and ethambutol, with good response.
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.
In this work the aim of study was the synthesis and evaluation of in vitro anti-Mycobacterium tub... more In this work the aim of study was the synthesis and evaluation of in vitro anti-Mycobacterium tuberculosis activity as well as the cytotoxicity in VERO cells of a series of 17 novel thiosemicarbazones derived from the natural monoterpene (-)-camphene by REMA and MTT methods. Overall, the majority of tested compounds exhibited considerable inhibitory effects on the growth of M. tuberculosis H 37 Rv, especially the derivatives 3, 4a-c, 4f, 4i, 4k, 5 and 6a-b. MIC values of 20 tested compounds ranged from 3.9 µg/mL to > 250 µg/mL. It was found that when inserting new nitrogenous groups to the (-)-camphene increased the anti-M. tuberculosis activity of some compounds. The SI was calculated for all compounds that showed highly potent anti-M. tuberculosis activity and the best SI values were 21.36, 26.92 and 31.62 (4b, 6a and 6b), and may be considered potential candidates for future antituberculosis drugs.
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.
O presente estudo objetivou avaliar o panorama epidemiológico da malária no estado do Amapá, deli... more O presente estudo objetivou avaliar o panorama epidemiológico da malária no estado do Amapá, delimitando o perfil de acometimento da doença e sua distribuição geográfica no estado, no período de janeiro de 2015 a dezembro de 2019. Trata-se de um estudo de caráter descritivo, e retrospectivo, a partir da coleta de dados no Sistema de Vigilância Epidemiológica (SIVEP-Malária), com posterior análise estatística descritiva, associativa e comparativa. Os resultados demonstram diminuição percentual e do Índice Parasitário Anual (IPA), das lâminas positivas para malária no estado, com os municípios de Serra do Navio, Calçoene, Mazagão e Pedra Branca do Amapari registrando os maiores valores médios de IPA. Evidenciou-se maior prevalência na faixa etária de 10 a 19 anos (24,8%), seguida pela faixa de 20 a 29 anos (21,5%); no sexo masculino (62,1%), em relação ao feminino (37,9%); nos indivíduos com menores níveis de escolaridade; e naqueles que desenvolvem atividades relacionadas à agricultura (46,44%) e à garimpagem (19,5%), quando desconsiderada a categoria "outras". A diminuição bruta e ajustada dos casos sugere possibilidade de controle da doença pela implementação de políticas de educação em saúde, conscientização para medidas preventivas, mecanismos para controle de vetores e estratégias de diagnóstico e tratamento precoces.
Revista Do Instituto De Medicina Tropical De Sao Paulo, Feb 15, 2018
The aim of this study was to determine the prevalence of GBS colonization in pregnant women in a ... more The aim of this study was to determine the prevalence of GBS colonization in pregnant women in a public health service. Methods: A study of 496 pregnant women at 35-37 gestational weeks was conducted from September 2011 to March 2014 in 21 municipalities of the 18 th Health Region of Paraná State. Vaginal and anorectal samples of each woman were plated on sheep blood agar, and in HPTH and Todd-Hewitt enrichment broths. Results: Of the 496 pregnant women, 141 (28.4%) were positive for GBS based on the combination of the three culture media with vaginal and anorectal samples. The prevalence was 23.7% for vaginal samples and 21.9% for anorectal ones. Among the variables analyzed in this study, only urinary infection was a significant factor (0.026) associated with GBS colonization in women. Conclusions: Based on these results, health units should performs universal screening of pregnant women and hospitals should provide adequate prophylaxis, when indicated.
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.
Essential oils from fresh Piperaceae leaves were obtained by hydrodistillation and analyzed by ga... more Essential oils from fresh Piperaceae leaves were obtained by hydrodistillation and analyzed by gas chromatography mass spectrometry (GC-MS), and a total of 68 components were identified. Principal components analysis results showed a chemical variability between species, with sesquiterpene compounds predominating in the majority of species analyzed. The composition of the essential oil of Piper mosenii was described for the first time. The cytotoxicity of the essential oils was evaluated in peritoneal macrophages and the oils of P. rivinoides, P. arboretum, and P. aduncum exhibited the highest values, with cytotoxic concentration at 50% (CC 50) > 200 µg/mL. Both P. diospyrifolium and P. aduncum displayed activity against Leishmania amazonensis, and were more selective for the parasite than for the macrophages, with a selectivity index (SI) of 2.35 and >5.52, respectively. These SI values were greater than the 1 for the standard drug pentamidine. The antileishmanial activity of the essential oils of P. diospyrifolium and P. aduncum was described for the first time. P. rivinoides, P. cernuum, and P. diospyrifolium displayed moderate activity against the Mycobacterium tuberculosis H 37 Rv bacillus, with a minimum inhibitory concentration (MIC) of 125 µg/mL. These results are relevant and suggests their potential for therapeutic purposes. Nevertheless, further studies are required to explain the exact mechanism of action of these essential oils.
se aumento de 68,64% da taxa de mortalidade geral, sendo que nos homens, esse aumento foi de 62,8... more se aumento de 68,64% da taxa de mortalidade geral, sendo que nos homens, esse aumento foi de 62,86%, e nas mulheres, de 92,65%. Quanto à causa de suicídio e à faixa etária, respectivamente, observou-se que a maioria ocorreu por lesão autoprovocada de forma intencional causada por enforcamento, estrangulamento e sufocação (X70), e o maior percentual de mortes foi entre 20 e 29 anos (35,05%), tanto no sexo masculino quanto no feminino. Conclusões: O suicídio é um problema complexo com grande impacto na saúde pública mundial e que vem apresentando crescimento nos últimos anos, como evidenciado neste estudo. Portanto, é salutar desenvolver análises epidemiológicas que auxiliem na identificação de grupos em risco de suicídio, a fim de compreender os aspectos envoltos nesse fenômeno, bem como seja possível adaptar intervenções para que haja maior eficácia e alcance na abordagem dessas populações.
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.
In developing nations, 10e20% of the human cases of tuberculosis are caused by Mycobacterium bovi... more In developing nations, 10e20% of the human cases of tuberculosis are caused by Mycobacterium bovis. However, this percentage may be underestimated because most laboratories in developing countries do not routinely perform mycobacterial cultures, and only a few have the systems in place to identify M. bovis. There are few studies investigating genotypic diversity and drug resistance in M. bovis from animal and/or human infections. The genotypic diversity of M. bovis strains obtained from bovine lymph nodes were investigated by spacer oligonucleotide typing (spoligotyping) and mycobacterial interspersed repetitive unitevariablenumber tandem repeat typing (MIRU-VNTR). The phenotypic resistance to isoniazid and rifampicin and MIC values of the isolates were determined using the resazurin microtiter assay plate method (REMA). The evaluation of the possible genetic basis for such resistance was performed with GenoType MTBDRplus. Sixty-seven isolates were obtained, of which 11 (16%) were MDR-TB, 8 (12%) were isoniazidresistant, and 2 (3%) were rifampicin-resistant. Mutations associated with drug resistance were not found. Genotyping techniques enabled the grouping of the strains into 12 clusters and 21 isolates with unique profiles. The high frequency of M. bovis reinforces the impact of the pathogen as a major causal agent of bovine tuberculosis in the study area. The resistance of the strains to drugs used for first-line treatment of human tuberculosis raises public health concerns. Further studies are required to elucidate the basis of drug resistance and genotypic diversity in M. bovis.
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