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2.
Parasit Vectors ; 13(1): 44, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32000835

RESUMO

BACKGROUND: Leishmania spp. are digenetic parasites capable of infecting humans and causing a range of diseases collectively known as leishmaniasis. The main mechanisms involved in the development and permanence of this pathology are linked to evasion of the immune response. Crosstalk between the immune system and particularities of each pathogenic species is associated with diverse disease manifestations. Lipophosphoglycan (LPG), one of the most important molecules present on the surface of Leishmania parasites, is divided into four regions with high molecular variability. Although LPG plays an important role in host-pathogen and vector-parasite interactions, the distribution and phylogenetic relatedness of the genes responsible for its synthesis remain poorly explored. The recent availability of full genomes and transcriptomes of Leishmania parasites offers an opportunity to leverage insight on how LPG-related genes are distributed and expressed by these pathogens. RESULTS: Using a phylogenomics-based framework, we identified a catalog of genes involved in LPG biosynthesis across 22 species of Leishmania from the subgenera Viannia and Leishmania, as well as 5 non-Leishmania trypanosomatids. The evolutionary relationships of these genes across species were also evaluated. Nine genes related to the production of the glycosylphosphatidylinositol (GPI)-anchor were highly conserved among compared species, whereas 22 genes related to the synthesis of the repeat unit presented variable conservation. Extensive gain/loss events were verified, particularly in genes SCG1-4 and SCA1-2. These genes act, respectively, on the synthesis of the side chain attached to phosphoglycans and in the transfer of arabinose residues. Phylogenetic analyses disclosed evolutionary patterns reflective of differences in host specialization, geographic origin and disease manifestation. CONCLUSIONS: The multiple gene gain/loss events identified by genomic data mining help to explain some of the observed intra- and interspecies variation in LPG structure. Collectively, our results provide a comprehensive catalog that details how LPG-related genes evolved in the Leishmania parasite specialization process.

3.
Pediatr Pulmonol ; 55(1): 169-176, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31553527

RESUMO

AIM: To compare the systemic cytokines/chemokines levels over time during the evolution of children hospitalized with community-acquired pneumonia (CAP) with and without pneumococcal infection. METHODS: Children less than 5-years-old hospitalized with CAP were prospectively investigated in Salvador, Brazil. Clinical data and biological samples were collected to investigate 20 etiological agents and to determine serum cytokines/chemokines levels on admission and 2 to 4 weeks later. Cases with pneumococcal infection received this diagnosis irrespective of also having other etiologies. RESULTS: A total of 277 patients were enrolled, however, serum sample was unavailable for cytokine measurement upon admission (n = 61) or upon follow-up visit (n = 36), etiology was undetected (n = 50) and one patient did not attend the follow-up visit. Therefore, this study group comprised of 129 cases with established etiology. The median (interquartile range) age and sampling interval was 18 (9-27) months and 18 (16-21) days, respectively. Established etiology was viral (52.0%), viral-bacterial (30.2%), and bacterial (17.8%). Pneumococcal infection was found in 31 (24.0%) patients. Overall, median interleukin-6 (IL-6; 10.6 [4.7-30.6] vs 21.0 [20.2-21.7]; P = .03), IL-10 (3.5 [3.1-4.5] vs 20.1 [19.8-20.4]; P < .001), and CCL2 (19.3 [12.4-23.2] vs 94.0 [67.2-117.8]; P < .001) were significantly higher in convalescent serum samples, whereas median CXCL10 (83.6 [36.4-182.9] vs 14.6 [0-116.6]; P < .001) was lower. Acute vs convalescent levels evolution of IL-10, CCL2, and CXCL10 did not differ among patients with or without pneumococcal infection. However, IL-6 decreased (27.8 [12.3-48.6] vs 20.8 [20.2-22.6]; P = .1) in patients with pneumococcal infection and increased (9.0 [4.2-22.6] vs 21.0 [20.2-21.7]; P = .001) in patients without it. CONCLUSION: The marked increase of IL-6 serum levels during the acute phase makes it a potential biomarker of pneumococcal infection among children with CAP.

4.
Vaccine ; 38(6): 1436-1443, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-31839468

RESUMO

Pathogenic bacteria, such as Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae and Moraxella catarrhalis, are important vaccine targets. The 10-valent pneumococcal conjugate vaccine (PCV10) acts on 10 differents S. pneumoniae serovars. However, this vaccine could also act on other bacteria genera, leading to dysbiosis. Moreover, the vaccination has also been associated with imbalances in the ratio between commensal and potentially pathogenic bacteria. Despite the wealth of studies assessing the influence of the microbiome on vaccine effects, how vaccination can influence the microbiome remains poorly understood. Herein, we assessed the effects of PCV10 on infant nasopharyngeal microbiome composition. Nasopharyngeal aspirates were collected from children with acute respiratory infection (ARI) aged 6-23 months. Two groups were composed of 48 vaccinated and 36 unvaccinated subjects. 16S ribosomal RNA sequencing was performed to assess bacterial composition and results were analyzed with QIIME. Similar bacterial compositions were observed in the unvaccinated and vaccinated samples. Principal component analysis also indicated a similar bacterial composition between the groups. In addition, bacterial diversity was not different between the vaccinated and unvaccinated samples. Accordingly, our results suggest that PCV10 vaccination promotes a specific response against its targets, thereby preserving the nosocomial microbiome. Although not statistically significant, Streptococcus and Haemophilus genera were increased in the vaccinated group, while Moraxella was decreased. Increases in Streptococcus may be associated with vaccine-target taxa replacement by non-pathogenic species. In sum, we observed that PCV10 vaccination acts by promoting a target-specific action against pathogenic bacteria and also induces commensal bacteria colonization without substantially changing the nasopharyngeal microbiome.

5.
Molecules ; 24(16)2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31443290

RESUMO

Background. There is no gold standard method for human skin odor determination; several techniques can be applied to collect, extract, transfer, and detect human skin odors. However, none of these methods are suitable for field sampling of a large number of individuals. Objective. The present study aimed to develop a simple, fast, non-invasive, and low-cost method for such a purpose. Methods. Considering that hair from legs can act as a retention mesh of volatile organic compounds (VOCs), samples of leg hairs provided by healthy adult males were collected and solid-phase microextraction (SPME), in headspace (HS) mode, coupled to gas chromatography (GC) and mass spectrometry (MS) analysis of the samples was carried out. A pilot test was applied to detect five quality markers that are frequently reported in human skin odors. Then, several steps were performed for method standardization. The method was applied to 36 different individuals (3 sampled under laboratory conditions and 33 under field conditions), aiming to evaluate its applicability in both environments. Findings. A total of 49 VOCs were identified, and 73.5% of these have been reported in previous studies. Main Conclusions. Hair from legs can be considered an efficient tool for human skin odor sampling and a suitable and practical matrix for human skin odor profile determination by using HS-SPME/GC-MS.


Assuntos
Cabelo/química , Odorantes/análise , Pele/metabolismo , Análise de Variância , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Microextração em Fase Sólida , Compostos Orgânicos Voláteis/análise , Compostos Orgânicos Voláteis/química , Compostos Orgânicos Voláteis/isolamento & purificação
6.
PLoS Negl Trop Dis ; 13(7): e0007484, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31318856

RESUMO

BACKGROUND: Visceral leishmaniasis (VL) is the most severe form of leishmaniasis and is potentially fatal if not diagnosed and treated. Accurate and timely diagnosis is considered one of the pillars needed for the reduction in disease-related lethality. Brazil is currently one of the three eco-epidemiological hotspots for this disease. Several serological tests are commercially available in this country for VL diagnosis, although information on the performance of these tests is fragmented and insufficient. The aim of this study was to directly compare the performance of six commercial kits: three enzyme-linked immunosorbent assays (ELISAs), two immunofluorescence antibody tests (IFATs), one immunochromatographic test (ICT), besides one ICT, currently not commercially available in Brazil and one in-house direct agglutination test (DAT-LPC), not yet marketed. METHODOLOGY/PRINCIPAL FINDINGS: A panel of 236 stored samples from patients with clinically suspected VL, including 77 HIV-infected patients, was tested. IT-LEISH and DAT-LPC showed the highest accuracy rate among the non-HIV-infected patients, 96.2% [CI95%: 92.8-99.7%] and 95.6% [CI95%: 91.9-99.3%], respectively. For the ELISA tests evaluated, the maximum accuracy was 91.2%, and in the inter HIV-status group analysis, no significant differences were observed. For both IFATs evaluated, the maximum accuracy was 84.3%, and a lower accuracy rate was observed among the HIV-infected patients (p = 0.039) than among the non-HIV-infected patients. The DAT-LPC was the most accurate test in the HIV-infected patients (p≤0.115). In general, no significant difference in accuracy was observed among the VL-suspected patients stratified by age. CONCLUSIONS/SIGNIFICANCE: In summary, the differences in the performance of the tests available for VL in Brazil confirm the need for local studies before defining the diagnostic strategy.


Assuntos
Anticorpos Antiprotozoários/sangue , Leishmaniose Visceral/diagnóstico , Kit de Reagentes para Diagnóstico/normas , Testes Sorológicos/normas , Adolescente , Adulto , Idoso , Testes de Aglutinação/métodos , Testes de Aglutinação/normas , Antígenos de Protozoários/sangue , Antígenos de Protozoários/imunologia , Brasil , Criança , Pré-Escolar , Ensaio de Imunoadsorção Enzimática/normas , Feminino , Técnica Direta de Fluorescência para Anticorpo/normas , Infecções por HIV/complicações , Infecções por HIV/parasitologia , Humanos , Imunoensaio/normas , Lactente , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Adulto Jovem
7.
Front Microbiol ; 9: 2475, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30473680

RESUMO

Acute respiratory infection (ARI) is the most frequent cause for hospitalization in infants and young children. Using multiplexed nCounter technology to digitally quantify 600 human mRNAs in parallel with 14 virus- and 5 bacterium-specific RNAs, we characterized viral and bacterial presence in nasopharyngeal aspirates (NPA) of 58 children with ARI and determined the corresponding in situ immune profiles. NPA contained different groups of organisms and these were classified into bacterial (n = 27), viral (n = 5), codetection [containing both viral and bacterial transcripts (n = 21), or indeterminate intermediate where microbial load is below threshold (n = 5)]. We then identified differentially expressed immune transcripts (DEITs) comparing NPAs from symptomatic children vs. healthy controls, and comparing children presenting NPAs with detectable microbial load vs. indeterminate. We observed a strong innate immune response in NPAs, due to the presence of evolutionarily conserved type I Interferon (IFN)-stimulated genes (ISG), which was correlated with total bacterial and/or viral load. In comparison with indeterminate NPAs, adaptive immunity transcripts discriminated among viral, bacterial, and codetected microbial profiles. In viral NPAs, B cell transcripts were significantly enriched among DEITs, while only type III IFN was correlated with viral load. In bacterial NPAs, myeloid cells and coinhibitory transcripts were enriched and significantly correlated with bacterial load. In conclusion, digital nCounter transcriptomics provide a microbial and immunological in situ "snapshot" of the nasopharyngeal interface in children with ARI. This enabled discrimination among viral, bacterial, codetection, and indeterminate transcripts in the samples using non-invasive sampling.

8.
Front Microbiol ; 9: 2283, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30323793

RESUMO

Leishmania braziliensis infection causes skin ulcers, typically found in localized cutaneous leishmaniasis (LCL). This tissue pathology associates with different modalities of cell necrosis, which are subverted by the parasite as a survival strategy. Herein we examined the participation of necroptosis, a specific form of programmed necrosis, in LCL lesions and found reduced RIPK3 and PGAM5 gene expression compared to normal skin. Assays using infected macrophages demonstrated that the parasite deactivates both RIPK3 and MLKL expression and that these molecules are important to control the intracellular L. braziliensis replication. Thus, LCL-related necroptosis may be targeted to control infection and disease immunopathology.

9.
PLoS One ; 13(9): e0203989, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30248113

RESUMO

BACKGROUND: Many studies have investigated what could attract insects of medical importance and a crucial role has lately been attributed to human skin odors. Most of these researches have been concerned with mosquitoes, e.g., vectors of dengue and malaria. Little is known about volatile organic compounds (VOCs) from human skin odors and their effects on leishmania vectors. OBJECTIVE: The present study aimed to identify the VOCs from human skin that can be attractive to female anthropophilic phlebotomine sandflies. RESULTS: Forty-two VOCs were identified from skin odors of 33 male volunteers, seven of which were tested in wind tunnel assays employing field-captured phlebotomine sandflies (75.4% identified as Lutzomyia intermedia). Hexane and (E)-oct-3-en-1-ol (octenol) were used as negative and positive controls, respectively. 2-Phenylacetaldehyde (hereafter called phenylacetaldehyde), 6-methylhept-5-en-2-one (also known as sulcatone), nonadecane and icosane were found to activate female phlebotomine sandflies, but only phenylacetaldehyde, 6-methylhepten-5-en-2-one and icosane elicited attraction responses. CONCLUSIONS: These results suggest that phenylacetaldehyde, 6-methylhepten-5-en-2-one and icosane may be suitable candidates for attractiveness experimentation in the field which can be an important tool to develop strategies concerning human beings protection against phlebotomine sandflies bites and consequently against leishmaniasis.


Assuntos
Insetos Vetores/fisiologia , Insetos Vetores/parasitologia , Leishmaniose Cutânea/transmissão , Odorantes/análise , Psychodidae/fisiologia , Psychodidae/parasitologia , Pele/química , Acetaldeído/análogos & derivados , Acetaldeído/análise , Adolescente , Adulto , Alcanos/análise , Animais , Brasil , Doenças Endêmicas , Feminino , Humanos , Mordeduras e Picadas de Insetos/prevenção & controle , Cetonas/análise , Leishmania/patogenicidade , Leishmaniose Cutânea/epidemiologia , Leishmaniose Cutânea/prevenção & controle , Masculino , Pessoa de Meia-Idade , Compostos Orgânicos Voláteis/análise , Compostos Orgânicos Voláteis/química , Adulto Jovem
10.
J Clin Virol ; 106: 34-40, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30031351

RESUMO

BACKGROUND: Virus-specific molecular assays such as real-time polymerase chain reaction (RT-PCR) are regularly used as the gold standard to diagnose viral respiratory tract infections, but simultaneous detection of multiple different pathogens is often challenging. A multiplex digital method of RNA quantification, nCounter (NanoString Technologies), can overcome this disadvantage and identify, in a single reaction, the presence of different respiratory viruses. OBJECTIVES: To evaluate the accuracy of nCounter to identify and quantify RSV-A and RSV-B in nasopharyngeal aspirates (NPA) of children (6-23-months-old) with acute respiratory infection. STUDY DESIGN: NPA was collected at enrolment in a prospective cross-sectional study conducted in Salvador, Brazil. A quantitative RT-PCR with a subgroup-specific primer and probeset for RSV-A and RSV-B was performed in parallel with a customized nCounter probeset containing viral targets in NPA. RESULTS: Of 559 NPA tested, RSV was detected by RT-PCR in 139 (24.9%), by nCounter in 122 (21.8%) and by any method in 158 (28.3%) cases. Compared to the gold standard of qRT-PCR, sensitivity of nCounter was 74.3% (95%CI:63.3%-82.9% RSV-A) and 77.6% (95%CI:66.3%-85.9% RSV-B); specificity was 98.4% (95%CI:96.8%-99.2% RSV-A) and 97.8% (95%CI:96.0%-98.8% RSV-B); positive predictive value was 87.3% (95%CI:76.9%-93.4% RSV-A) and 82.5% (95%CI:71.4%-90.0% RSV-B) and negative predictive value was 96.1% (95%CI:94.1%-97.5% RSV-A), and 96.9% (95%CI:95.1%-98.2% RSV-B). Accuracy was 95.2% (95%CI:93.1%-96.7%) for RSV-A and 95.3% (95%CI:93.3%-96.9%) for RSV-B, while both methods significantly correlated for RSV-A (r = 0.44, p = 8 × 10-5) and RSV-B (r = 0.73, p = 3 × 10-12) quantification. CONCLUSIONS: nCounter is highly accurate in detecting RSV-A/B in NPA. Robustness and high-throughput multiplexing indicate its use in large-scale epidemiological studies.


Assuntos
Técnicas de Diagnóstico Molecular/métodos , Reação em Cadeia da Polimerase Multiplex/métodos , RNA Viral/análise , Infecções Respiratórias/diagnóstico , Doença Aguda/epidemiologia , Brasil/epidemiologia , Estudos Transversais , Feminino , Humanos , Lactente , Masculino , Nasofaringe/virologia , Estudos Prospectivos , Reprodutibilidade dos Testes , Vírus Sincicial Respiratório Humano/genética , Vírus Sincicial Respiratório Humano/isolamento & purificação , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/virologia , Sensibilidade e Especificidade
11.
Front Immunol ; 9: 640, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29670621

RESUMO

Localized cutaneous leishmaniasis (LCL) is a chronic disease characterized by ulcerated skin lesion(s) and uncontrolled inflammation. The mechanisms underlying the pathogenesis of LCL are not completely understood, and little is known about posttranscriptional regulation during LCL. MicroRNAs (miRNAs) are non-coding small RNAs that regulate gene expression and can be implicated in the pathogenesis of LCL. We investigated the involvement of miRNAs and their targets genes in human LCL using publicly available transcriptome data sets followed by ex vivo validation. Initial analysis highlighted that miRNA expression is altered during LCL, as patients clustered separately from controls. Joint analysis identified eight high confidence miRNAs that had altered expression (-1.5 ≤ fold change ≥ 1.5; p < 0.05) between cutaneous ulcers and uninfected skin. We found that the expression of miR-193b and miR-671 are greatly associated with their target genes, CD40 and TNFR, indicating the important role of these miRNAs in the expression of genes related to the inflammatory response observed in LCL. In addition, network analysis revealed that miR-193b, miR-671, and TREM1 correlate only in patients who show faster wound healing (up to 59 days) and not in patients who require longer cure times (more than 60 days). Given that these miRNAs are associated with control of inflammation and healing time, our findings reveal that they might influence the pathogenesis and prognosis of LCL.


Assuntos
Leishmania braziliensis/fisiologia , Leishmaniose Cutânea/genética , MicroRNAs/genética , Receptor Gatilho 1 Expresso em Células Mieloides/genética , Biomarcadores Farmacológicos , Antígenos CD40/genética , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Leishmaniose Cutânea/tratamento farmacológico , Receptores Tipo I de Fatores de Necrose Tumoral/genética , Fenômenos Fisiológicos da Pele/genética , Resultado do Tratamento , Cicatrização/genética
12.
Diagn Microbiol Infect Dis ; 91(4): 312-318, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29653798

RESUMO

Hsp70 is a cytoplasmic heat-shock protein, encoded by a multicopy tandemly repeated gene that has recently been gaining popularity as a valuable marker for typing Leishmania species. In this study, we used a previously described hsp70 PCR-RFLP method for identifying Brazilian Leishmania isolates. We identified two distinct L. (L.) amazonensis hsp70 alleles that resulted in two different RFLP patterns. Also, we found RFLP polymorphisms amongst L. (Viannia) naiffi strains. The profiles of both L. (V.) shawi and L. (V.) lindenbergi were very similar to those of other L. (Viannia) species. The observations described herein reflect the polymorphism found within species of Leishmania and indicate that results from this hsp70 PCR-RFLP method should be used with caution when typing isolates from clinical cases of leishmaniasis and Leishmania species from Brazil.


Assuntos
Proteínas de Choque Térmico HSP70/genética , Leishmania/genética , Leishmaniose Cutânea/parasitologia , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição/genética , Proteínas de Protozoários/genética , Alelos , Animais , Brasil , DNA de Protozoário/genética , Genoma de Protozoário/genética , Humanos , Leishmania/classificação , Leishmania braziliensis/genética , Leishmaniose Cutânea/diagnóstico , Filogenia , Análise de Sequência de DNA
13.
Artigo em Inglês | MEDLINE | ID: mdl-29675401

RESUMO

Different members of intracellular protein families are recognized by the immune system of the vertebrate host infected by parasites of the genus Leishmania. Here, we have analyzed the antigenic and immunogenic properties of the Leishmania eIF2 and eIF2B translation initiation factors. An in silico search in Leishmania infantum sequence databases allowed the identification of the genes encoding the α, ß, and γ subunits and the α, ß, and δ subunits of the putative Leishmania orthologs of the eukaryotic initiation factors F2 (LieIF2) or F2B (LieIF2B), respectively. The antigenicity of these factors was analyzed by ELISA using recombinant versions of the different subunits. Antibodies against the different LieIF2 and LieIF2B subunits were found in the sera from human and canine visceral leishmaniasis patients, and also in the sera from hamsters experimentally infected with L. infantum. In L. infantum (BALB/c) and Leishmania major (BALB/c or C57BL/6) challenged mice, a moderate humoral response against these protein factors was detected. Remarkably, these proteins elicited an IL-10 production by splenocytes derived from infected mice independently of the Leishmania species employed for experimental challenge. When DNA vaccines based on the expression of the LieIF2 or LieIF2B subunit encoding genes were administered in mice, an antigen-specific secretion of IFN-γ and IL-10 cytokines was observed. Furthermore, a partial protection against murine CL development due to L. major infection was generated in the vaccinated mice. Also, in this work we show that the LieIF2α subunit and the LieIF2Bß and δ subunits have the capacity to stimulate IL-10 secretion by spleen cells from naïve mice. B-lymphocytes were identified as the major producers of this anti-inflammatory cytokine. Taking into account the data found in this study, it may be hypothesized that these proteins act as virulence factors implicated in the induction of humoral responses as well as in the production of the down-regulatory IL-10 cytokine, favoring a pathological outcome. Therefore, these proteins might be considered markers of disease.


Assuntos
Antígenos de Bactérias/imunologia , Fator de Iniciação 2B em Eucariotos/imunologia , Fator de Iniciação 2 em Eucariotos/imunologia , Leishmania infantum/imunologia , Leishmaniose/imunologia , Animais , Linfócitos B/imunologia , Biomarcadores , Cricetinae , Fator de Iniciação 2 em Eucariotos/genética , Fator de Iniciação 2B em Eucariotos/genética , Feminino , Interferon gama/metabolismo , Interleucina-10/metabolismo , Leishmania infantum/patogenicidade , Leishmaniose/microbiologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Vacinas de DNA/imunologia
14.
Arq. bras. cardiol ; 110(3): 240-245, Mar. 2018. tab, graf
Artigo em Inglês | LILACS-Express | ID: biblio-888042

RESUMO

Abstract Background: The cardiovascular risk burden among diverse indigenous populations is not totally known and may be influenced by lifestyle changes related to the urbanization process. Objectives: To investigate the cardiovascular (CV) mortality profile of indigenous populations during a rapid urbanization process largely influenced by governmental infrastructure interventions in Northeast Brazil. Methods: We assessed the mortality of indigenous populations (≥ 30 y/o) from 2007 to 2011 in Northeast Brazil (Bahia and Pernambuco states). Cardiovascular mortality was considered if the cause of death was in the ICD-10 CV disease group or if registered as sudden death. The indigenous populations were then divided into two groups according to the degree of urbanization based on anthropological criteria:9,10 Group 1 - less urbanized tribes (Funi-ô, Pankararu, Kiriri, and Pankararé); and Group 2 - more urbanized tribes (Tuxá, Truká, and Tumbalalá). Mortality rates of highly urbanized cities (Petrolina and Juazeiro) in the proximity of indigenous areas were also evaluated. The analysis explored trends in the percentage of CV mortality for each studied population. Statistical significance was established for p value < 0.05. Results: There were 1,333 indigenous deaths in tribes of Bahia and Pernambuco (2007-2011): 281 in Group 1 (1.8% of the 2012 group population) and 73 in Group 2 (3.7% of the 2012 group population), CV mortality of 24% and 37%, respectively (p = 0.02). In 2007-2009, there were 133 deaths in Group 1 and 44 in Group 2, CV mortality of 23% and 34%, respectively. In 2009-2010, there were 148 deaths in Group 1 and 29 in Group 2, CV mortality of 25% and 41%, respectively. Conclusions: Urbanization appears to influence increases in CV mortality of indigenous peoples living in traditional tribes. Lifestyle and environmental changes due to urbanization added to suboptimal health care may increase CV risk in this population.


Resumo Fundamento: O risco cardiovascular das diversas comunidades indígenas não está bem estabelecido e pode ser influenciado pelo processo de urbanização a que se submetem esses povos. Objetivos: Investigar o perfil da mortalidade cardiovascular (CV) das populações indígenas durante o rápido processo de urbanização altamente influenciado por intervenções governamentais de infraestrutura no Nordeste do Brasil. Métodos: Avaliamos a mortalidade de populações indígenas (≥ 30 anos) do Vale do São Francisco (Bahia e Pernambuco) no período de 2007-2011. Considerou-se mortalidade CV se a causa de morte constasse no grupo de doenças CV do CID-10 ou se tivesse sido registrada como morte súbita. As populações indígenas foram divididas em dois grupos conforme o grau de urbanização baseado em critérios antropológicos: Grupo 1 - menos urbanizadas (Funi-ô, Pankararu, Kiriri e Pankararé); e Grupo 2 - mais urbanizadas (Tuxá, Truká e Tumbalalá). Taxas de mortalidade de cidades altamente urbanizadas (Petrolina e Juazeiro) nas proximidades das áreas indígenas foram também avaliadas. A análise explorou tendências na porcentagem de mortalidade CV para cada população estudada. Adotou-se o valor de p < 0,05 como significância estatística. Resultados: Houve 1.333 mortes indígenas nas tribos da Bahia e de Pernambuco (2007-2011): 281 no Grupo 1 (1,8% da população de 2012) e 73 no Grupo 2 (3,7% da população de 2012), mortalidade CV de 24% e 37%, respectivamente (p = 0,02). Entre 2007 e 2009, houve 133 mortes no Grupo 1 e 44 no Grupo 2, mortalidade CV de 23% e 34%, respectivamente. Entre 2009 e 2010, houve 148 mortes no Grupo 1 e 29 no Grupo 2, mortalidade CV de 25% e 41%, respectivamente. Conclusões: A urbanização parece influenciar os aumentos de mortalidade CV dos povos indígenas vivendo de modo tradicional. Mudanças no estilo de vida e ambientais devidas à urbanização somadas à subótima atenção à saúde podem estar implicadas no aumento do risco CV nos povos indígenas.

15.
Arq Bras Cardiol ; 110(3): 240-245, 2018 Mar.
Artigo em Português, Inglês | MEDLINE | ID: mdl-29466492

RESUMO

BACKGROUND: The cardiovascular risk burden among diverse indigenous populations is not totally known and may be influenced by lifestyle changes related to the urbanization process. OBJECTIVES: To investigate the cardiovascular (CV) mortality profile of indigenous populations during a rapid urbanization process largely influenced by governmental infrastructure interventions in Northeast Brazil. METHODS: We assessed the mortality of indigenous populations (≥ 30 y/o) from 2007 to 2011 in Northeast Brazil (Bahia and Pernambuco states). Cardiovascular mortality was considered if the cause of death was in the ICD-10 CV disease group or if registered as sudden death. The indigenous populations were then divided into two groups according to the degree of urbanization based on anthropological criteria:9,10 Group 1 - less urbanized tribes (Funi-ô, Pankararu, Kiriri, and Pankararé); and Group 2 - more urbanized tribes (Tuxá, Truká, and Tumbalalá). Mortality rates of highly urbanized cities (Petrolina and Juazeiro) in the proximity of indigenous areas were also evaluated. The analysis explored trends in the percentage of CV mortality for each studied population. Statistical significance was established for p value < 0.05. RESULTS: There were 1,333 indigenous deaths in tribes of Bahia and Pernambuco (2007-2011): 281 in Group 1 (1.8% of the 2012 group population) and 73 in Group 2 (3.7% of the 2012 group population), CV mortality of 24% and 37%, respectively (p = 0.02). In 2007-2009, there were 133 deaths in Group 1 and 44 in Group 2, CV mortality of 23% and 34%, respectively. In 2009-2010, there were 148 deaths in Group 1 and 29 in Group 2, CV mortality of 25% and 41%, respectively. CONCLUSIONS: Urbanization appears to influence increases in CV mortality of indigenous peoples living in traditional tribes. Lifestyle and environmental changes due to urbanization added to suboptimal health care may increase CV risk in this population.


Assuntos
Doenças Cardiovasculares/etnologia , Doenças Cardiovasculares/mortalidade , Índios Sul-Americanos/estatística & dados numéricos , Urbanização/tendências , Adulto , Distribuição por Idade , Idoso , Brasil/etnologia , Causas de Morte , Feminino , Humanos , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Fatores de Tempo , População Urbana/estatística & dados numéricos , População Urbana/tendências
16.
J. pediatr. (Rio J.) ; 94(1): 23-30, Jan.-Feb. 2018. tab, graf
Artigo em Inglês | LILACS-Express | ID: biblio-894095

RESUMO

Abstract Objective: Community-acquired pneumonia is an important cause of morbidity in childhood, but the detection of its causative agent remains a diagnostic challenge. The authors aimed to evaluate the role of the chest radiograph to identify cases of community-aquired pneumonia caused by typical bacteria. Methods: The frequency of infection by Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis was compared in non-hospitalized children with clinical diagnosis of community acquired pneumonia aged 2-59 months with or without radiological confirmation (n = 249 and 366, respectively). Infection by S. pneumoniae was diagnosed by the detection of a serological response against at least one of eight pneumococcal proteins (defined as an increase ≥2-fold in the IgG levels against Ply, CbpA, PspA1 and PspA2, PhtD, StkP-C, and PcsB-N, or an increase ≥1.5-fold against PcpA). Infection by H. influenzae and M. catarrhalis was defined as an increase ≥2-fold on the levels of microbe-specific IgG. Results: Children with radiologically confirmed pneumonia had higher rates of infection by S. pneumoniae. The presence of pneumococcal infection increased the odds of having radiologically confirmed pneumonia by 2.8 times (95% CI: 1.8-4.3). The negative predictive value of the normal chest radiograph for infection by S. pneumoniae was 86.3% (95% CI: 82.4-89.7%). There was no difference on the rates of infection by H. influenzae and M. catarrhalis between children with community-acquired pneumonia with and without radiological confirmation. Conclusions: Among children with clinical diagnosis of community-acquired pneumonia submitted to chest radiograph, those with radiologically confirmed pneumonia present a higher rate of infection by S. pneumoniae when compared with those with a normal chest radiograph.


Resumo Objetivo: Avaliar o papel do raios X de tórax na identificação de casos de pneumonia adquirida na comunidade (PAC) causada por agentes bacterianos. Métodos: A frequência de infecção por Streptococcus pneumoniae, Haemophilus influenzae e Moraxella catarrhalis em crianças com PAC não hospitalizadas foi comparada com a presença de confirmação radiológica da pneumonia (n = 249 crianças com pneumonia radiologicamente confirmada e 366 crianças com raios X de tórax normal). Infecção por S. pneumoniae foi diagnosticada com base na resposta sorológica a pelo menos uma dentre oito proteínas pneumocócicas investigadas (aumento ≥ 2 vezes nos níveis de IgG em relação a Ply, CbpA, PspA1 e 2, PhtD, StkP-C e PcsB-N ou aumento≥ 1,5 vez em relação aPcpA). Infecção por H. influenzae e M. catarrhalis foi definida por aumento ≥ 2 vezes nos níveis de IgG específica a antígenos de cada agente. Resultados: Crianças com pneumonia radiologicamente confirmada apresentaram maior taxa de infecção pelo pneumococo. Além disso, a presença de infecção pneumocócica foi um fator preditor de pneumonia radiologicamente confirmada, o que aumenta sua chance de detecção em 2,8 vezes (IC 95%: 1,8-4,3). O valor preditivo negativo do raios X normal para a infecção por S. pneumoniae foi 86,3% (IC95%: 82,4%-89,7%). Não houve diferença nas frequências de infecção por H. influenzae e M. catarrhalis entre crianças com PAC com ou sem confirmação radiológica. Conclusão: Crianças com diagnóstico clínico de PAC submetidas a um raios X de tórax que apresentam confirmação radiológica têm maior taxa de infecção por S. pneumoniae comparadas com as crianças com raios X normal.

17.
Cytokine ; 107: 1-8, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29158121

RESUMO

Community-acquired pneumonia (CAP) is the main cause of death in children under-5 years worldwide and Streptococcus pneumoniae is the most common bacterial agent. However, it is difficult to identify pneumococcal infection among children with CAP. We aimed to assess association between any cytokine/chemokine and pneumococcal infection in childhood CAP. Furthermore, we evaluated the diagnostic value of cytokine/chemokine for pneumococcal infection. This prospective study was conducted at an Emergency Room, in Salvador, Brazil. Children <5-years-old hospitalized with CAP in a 21-month period were evaluated. On admission, clinical and radiological data were collected along with biological samples to investigate 20 etiological agents and determine serum cytokines (interleukin (IL)-8, IL-6, IL-10, IL-1ß, IL-12, TNF-α, IL-2, IL-4, IL-5, γ-interferon), and chemokines (CCL2, CCL5, CXCL9, CXCL10) concentration. From 166 patients with etiology detected, pneumococcal infection was detected in 38 (22.9%) cases among which the median IL-6(pg/ml) was 31.2 (IQR: 12.4-54.1). The other 128 cases had other causative agents detected (Haemophilus influenzae, Moraxella catarrhalis, atypical bacteria and viruses) with the median IL-6 concentration being 9.0 (IQR: 4.1-22.0; p < 0.001). The area under the ROC curve for IL-6 to predict pneumococcal CAP was 0.74 (95%CI: 0.65-0.83; p < 0.001). By multivariate analysis, with pneumococcal CAP as dependent variable, IL-6 was an independent predictor for pneumococcal infection (OR = 5.56; 95%CI: 2.42-12.75, cut-off point = 12.5 pg/ml; p = 0.0001). The negative predictive value of IL-6 under 12.5 pg/ml for pneumococcal infection was 90% (95%CI: 82-95%). Independently significant difference was not found for any other cytokines/chemokines. Serum IL-6 concentration on admission is independently associated with pneumococcal infection among children under-5 years hospitalized with CAP.


Assuntos
Quimiocinas/sangue , Infecções Comunitárias Adquiridas/diagnóstico , Citocinas/sangue , Hospitalização/estatística & dados numéricos , Pneumonia Pneumocócica/diagnóstico , Brasil , Pré-Escolar , Infecções Comunitárias Adquiridas/sangue , Infecções Comunitárias Adquiridas/microbiologia , Feminino , Humanos , Lactente , Interleucina-6/sangue , Masculino , Pneumonia Pneumocócica/sangue , Pneumonia Pneumocócica/microbiologia , Estudos Prospectivos , Streptococcus pneumoniae/fisiologia
18.
J Pediatr (Rio J) ; 94(1): 23-30, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-28668258

RESUMO

OBJECTIVE: Community-acquired pneumonia is an important cause of morbidity in childhood, but the detection of its causative agent remains a diagnostic challenge. The authors aimed to evaluate the role of the chest radiograph to identify cases of community-aquired pneumonia caused by typical bacteria. METHODS: The frequency of infection by Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis was compared in non-hospitalized children with clinical diagnosis of community acquired pneumonia aged 2-59 months with or without radiological confirmation (n=249 and 366, respectively). Infection by S. pneumoniae was diagnosed by the detection of a serological response against at least one of eight pneumococcal proteins (defined as an increase ≥2-fold in the IgG levels against Ply, CbpA, PspA1 and PspA2, PhtD, StkP-C, and PcsB-N, or an increase ≥1.5-fold against PcpA). Infection by H. influenzae and M. catarrhalis was defined as an increase ≥2-fold on the levels of microbe-specific IgG. RESULTS: Children with radiologically confirmed pneumonia had higher rates of infection by S. pneumoniae. The presence of pneumococcal infection increased the odds of having radiologically confirmed pneumonia by 2.8 times (95% CI: 1.8-4.3). The negative predictive value of the normal chest radiograph for infection by S. pneumoniae was 86.3% (95% CI: 82.4-89.7%). There was no difference on the rates of infection by H. influenzae and M. catarrhalis between children with community-acquired pneumonia with and without radiological confirmation. CONCLUSIONS: Among children with clinical diagnosis of community-acquired pneumonia submitted to chest radiograph, those with radiologically confirmed pneumonia present a higher rate of infection by S. pneumoniae when compared with those with a normal chest radiograph.


Assuntos
Infecções por Haemophilus/diagnóstico por imagem , Infecções por Moraxellaceae/diagnóstico por imagem , Pneumonia Bacteriana/diagnóstico por imagem , Pneumonia Bacteriana/microbiologia , Radiografia Torácica , Anticorpos Antibacterianos/sangue , Antígenos de Bactérias/sangue , Pré-Escolar , Infecções Comunitárias Adquiridas/diagnóstico por imagem , Infecções Comunitárias Adquiridas/microbiologia , Feminino , Haemophilus influenzae/imunologia , Haemophilus influenzae/isolamento & purificação , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Lactente , Masculino , /isolamento & purificação , Pneumonia Pneumocócica/diagnóstico por imagem , Estudos Prospectivos , Sensibilidade e Especificidade , Streptococcus pneumoniae/imunologia , Streptococcus pneumoniae/isolamento & purificação
20.
Front Immunol ; 8: 1127, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28959260

RESUMO

Leishmania parasites infect macrophages, causing a wide spectrum of human diseases, from cutaneous to visceral forms. In search of novel therapeutic targets, we performed comprehensive in vitro and ex vivo mapping of the signaling pathways upstream and downstream of antioxidant transcription factor [nuclear factor erythroid 2-related factor 2 (Nrf2)] in cutaneous leishmaniasis (CL), by combining functional assays in human and murine macrophages with a systems biology analysis of in situ (skin biopsies) CL patient samples. First, we show the PKR pathway controls the expression and activation of Nrf2 in Leishmania amazonensis infection in vitro. Nrf2 activation also required PI3K/Akt signaling and autophagy mechanisms. Nrf2- or PKR/Akt-deficient macrophages exhibited increased levels of ROS/RNS and reduced expression of Sod1 Nrf2-dependent gene and reduced parasite load. L. amazonensis counteracted the Nrf2 inhibitor Keap1 through the upregulation of p62 via PKR. This Nrf2/Keap1 observation was confirmed in situ in skin biopsies from Leishmania-infected patients. Next, we explored the ex vivo transcriptome in CL patients, as compared to healthy controls. We found the antioxidant response element/Nrf2 signaling pathway was significantly upregulated in CL, including downstream target p62. In silico enrichment analysis confirmed upstream signaling by interferon and PI3K/Akt, and validated our in vitro findings. Our integrated in vitro, ex vivo, and in silico approach establish Nrf2 as a central player in human cutaneous leishmaniasis and reveal Nrf2/PKR crosstalk and PI3K/Akt pathways as potential therapeutic targets.

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