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1.
Lancet Infect Dis ; 2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-39116904

RESUMO

BACKGROUND: A single-dose dengue vaccine that protects individuals across a wide age range and regardless of dengue serostatus is an unmet need. We assessed the safety and efficacy of the live, attenuated, tetravalent Butantan-dengue vaccine (Butantan-DV) in adults, adolescents, and children. We previously reported the primary and secondary efficacy and safety endpoints in the initial 2 years of follow-up. Here we report the results through an extended follow-up period, with an average of 3·7 years of follow-up. METHODS: In this double-blind, randomised, placebo-controlled, phase 3, multicentre trial in Brazil, healthy participants (aged 2-59 years) who had not previously received a dengue vaccine were enrolled and randomly assigned 2:1 (stratified by age 18-59 years, 7-17 years, and 2-6 years) using a central electronic randomisation system to receive 0·5 mL of Butantan-DV (containing approximately 103 plaque-forming units of each of the four vaccine virus strains) or placebo, administered subcutaneously. Syringes containing vaccine or placebo were prepared by an unmasked trial pharmacist who was not involved in any subsequent participant assessments; other site staff and the participants remained unaware of the group allocations. Vaccine efficacy was calculated with the accrual of virologically confirmed dengue (VCD) cases (by RT-PCR) at least 28 days after vaccination up until the cutoff (at least 2 years of follow-up from the last participant enrolled). The primary endpoint was vaccine efficacy against VCD after day 28 by any dengue virus (DENV) serotype regardless of dengue serostatus at baseline in the per-protocol population. The primary and secondary safety endpoints up until day 21 were previously reported; secondary safety endpoints include the frequency of unsolicited vaccine-related adverse events after day 22. Safety analyses were done on all participants as treated. This trial is registered with ClinicalTrials.gov (NCT02406729) and is ongoing. FINDINGS: Of 16 363 participants assessed for eligibility, 16 235 were randomly assigned between Feb 22, 2016, and July 5, 2019, and received single-dose Butantan-DV (10 259 participants) or placebo (5976 participants). 16 162 participants (Butantan-DV n=10 215; placebo n=5947) were included in the per-protocol population and 16 235 (Butantan-DV n=10 259; placebo n=5976) in the safety population. At the data cutoff (July 13, 2021), participants had 2-5 years of follow-up (mean 3·7 years [SD 1·0], median 4·0 years [IQR 3·2-4·5]). 356 VCD cases were captured through the follow-up (128 in the vaccine group and 228 in the placebo group). Vaccine efficacy against VCD caused by any DENV serotype was 67·3% (95% CI 59·4-73·9); cases caused by DENV-3 or DENV-4 were not observed. The proportions of participants who had serious adverse events were similar between treatment groups (637 [6·2%] in the vaccine group and 395 [6·6%] in the placebo group) up until the cutoff. INTERPRETATION: A single dose of Butantan-DV was generally well tolerated and efficacious against symptomatic VCD (caused by DENV-1 and DENV-2) for a mean of 3·7 years. These findings support the continued development of Butantan-DV to prevent dengue disease in children, adolescents, and adults regardless of dengue serostatus. FUNDING: Instituto Butantan and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co. TRANSLATIONS: For the Spanish and Portuguese translations of the abstract see Supplementary Materials section.

2.
Clin Genet ; 106(5): 644-649, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39015008

RESUMO

Limb-girdle muscular dystrophy type 2G/R7 (LGMD2G/R7) is an ultra-rare condition initially identified within the Brazilian population. We aimed to expand clinical and genetic information about this disease, including its worldwide distribution. A multicenter historical cohort study was performed at 13 centers in Brazil in which data from index cases and their affected relatives from consecutive families with LGMD2G/R7 were reviewed from July 2017 to August 2023. Additionally, a systematic literature review was conducted to identify case reports and series of the disease worldwide. Forty-one LGMD2G/R7 cases were described in the Brazilian cohort, being all subjects homozygous for the c.157C>T/(p.Gln53*) variant in TCAP. Survival curves showed that the median disease duration before individuals required walking aids was 21 years. Notably, women exhibited a slower disease progression, requiring walking aids 13 years later than men. LGMD2G/R7 was frequently reported not only in Brazil but also in China and Bulgaria, with 119 cases identified globally, with possible founder effects in the Brazilian, Eastern European, and Asian populations. These findings are pivotal in raising awareness of LGMD2G/R7, understanding its progression, and identifying potential modifiers. This can significantly contribute to the development of future natural history studies and clinical trials for this disease.


Assuntos
Distrofia Muscular do Cíngulo dos Membros , Mutação , Humanos , Distrofia Muscular do Cíngulo dos Membros/genética , Distrofia Muscular do Cíngulo dos Membros/epidemiologia , Distrofia Muscular do Cíngulo dos Membros/diagnóstico , Masculino , Brasil/epidemiologia , Feminino , Adulto , Adolescente , Pessoa de Meia-Idade , Criança , Estudos de Coortes , Adulto Jovem , Linhagem , Conectina/genética , Fenótipo , Predisposição Genética para Doença , Pré-Escolar
3.
Talanta ; 278: 126513, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-38970965

RESUMO

In this work, the electrochemical behavior of the glycosylated flavonoid kaempferitrin was studied, and an electroanalytical methodology was developed for its determination in infusions of Bauhinia forficata using a boron-doped diamond electrode (BDD). The electrochemical behavior of the flavonoid was studied by cyclic voltammetry, and two irreversible oxidation peaks at 0.80 and 1.0 V vs Ag/AgCl were observed. The influence of the pH on the voltammograms was examined, and higher sensitivity was found at pH 7.0. The electrochemical process corresponding to peak 1 at 0.80 V is predominantly diffusion-controlled, as the study shows at varying scan rates. An analytical plot was obtained by square wave voltammetry at optimized experimental conditions (frequency = 100 s-1, amplitude = 90 mV, and step potential = 8 mV) in the concentration range from 3.4 µmol L-1 to 58 µmol L-1, with a linearity of 0.99. The limit of detection and limit of quantification values were 1.0 µmol L-1 and 3.4 µmol L-1, respectively. Three samples of Bauhinia forficata infusions (2 g of sample in 100 mL of water) were analyzed, and the KF values found were 5.0 × 10-4 mol L-1, 3.0 × 10-4 mol L-1, and 7.0 × 10-4 mol L-1, with recovery percentages of 98 %, 106 % and 94 %, respectively. Finally, experiments were performed with two other flavonoids (chrysin and apeginin) to compare and propose an electrochemical oxidation mechanism for kaempferitrin, which was supported by quantum chemical calculations.


Assuntos
Técnicas Eletroquímicas , Quempferóis , Oxirredução , Quempferóis/química , Quempferóis/análise , Técnicas Eletroquímicas/métodos , Glicosilação , Eletrodos , Bauhinia/química , Teoria Quântica , Flavonoides/química , Flavonoides/análise , Limite de Detecção , Diamante/química
4.
Pediatr Transplant ; 28(5): e14814, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38895799

RESUMO

There are no standard management protocols for the treatment of bile leak (BL) after liver transplantation. The objective of this study is to describe treatment options for BL after pediatric LT. METHODS: Retrospective analysis (January 2010-March 2023). VARIABLES STUDIED: preoperative data, status at diagnosis, and postoperative outcome. Four groups: observation (n = 9), percutaneous transhepatic cholangiography (PTC, n = 38), ERCP (2), and surgery (n = 27). RESULTS: Nine hundred and thirty-one pediatric liver transplantation (859 LDLT and 72 DDT); 78 (8.3%) patients had BL, all in LDLT. The median (IQR) peritoneal bilirubin (PB) level and fluid-to-serum bilirubin ratio (FSBR) at diagnosis was 14.40 mg/dL (8.5-29), and 10.7 (4.1-23.7). Patients who required surgery for treatment underwent the procedure earlier, at a median of 14 days (IQR: 7-19) versus 22 days for PTC (IQR: 15-27, p = 0.002). PB and FSBR were significantly lower in the observation group. In 11 cases, conservative management had resolution of the BL in an average time of 35 days, and 38 patients underwent PTC in a median time of 22 days (15-27). Twenty-seven (34.6%) patients were reoperated as initial treatment for BL in a median time of 17 days (1-108 days); 25 (33%) patients evolved with biliary stricture, 5 (18.5%) after surgery, and 20 (52.6%) after PTC (p = 0.01). CONCLUSION: Patients with BL who were observed presented significantly lower levels of PB and FSBR versus those who underwent PTC or surgery. Patients treated with PTC presented higher rates of biliary stricture during the follow-up.


Assuntos
Transplante de Fígado , Complicações Pós-Operatórias , Humanos , Estudos Retrospectivos , Masculino , Feminino , Lactente , Pré-Escolar , Criança , Complicações Pós-Operatórias/terapia , Complicações Pós-Operatórias/etiologia , Colangiopancreatografia Retrógrada Endoscópica , Colangiografia , Adolescente , Bile , Resultado do Tratamento
5.
Malar J ; 23(1): 162, 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38783318

RESUMO

BACKGROUND: Health information systems (HIS) are a pivotal element in epidemiological surveillance. In Brazil, malaria persists as a public health challenge, with 99% of its occurrences concentrated in the Amazon region, where cases are reported through the HIS Sivep-Malaria. Recent technological advancements indicate that case notifications can be expedited through more efficient systems with broader coverage. The objective of this study is to analyse opportunities for notification within Sivep-Malaria and explore the implementation of mobile electronic devices and applications to enhance the performance of malaria case notifications and use. METHODS: This descriptive study analyses data on malaria-positive cases in the Brazilian Amazon from 2004 to 2022. Malaria Epidemiological Surveillance System (Sivep-Malaria) data were used. The Brazilian Amazon region area is approximately 5 million km2 across nine different states in Brazil. Data entry opportunities were assessed by considering the time difference between the 'date of data entry' and the 'date of notification.' Descriptive statistics, including analyses of means and medians, were conducted across the entire Amazon region, and for indigenous population villages and gold mining areas. RESULTS: Between 2004 and 2022, 6,176,878 new malaria cases were recorded in Brazil. The average data entry opportunity throughout the period was 17.9 days, with a median of 8 days. The most frequently occurring value was 1 day, and 99% of all notifications were entered within 138 days, with 75.0% entered within 20 days after notification. The states with the poorest data entry opportunities were Roraima and Tocantins, with averages of 31.3 and 31.0 days, respectively. For indigenous population villages and gold mining areas, the median data entry opportunities were 23 and 15 days, respectively. CONCLUSIONS: In malaria elimination, where surveillance is a primary strategy for evaluating each reported case, reducing notification time, enhancing data quality and being able to follow-up cases through computerized reports offer significant benefits for cases investigation. Technological improvements in Sivep-Malaria could yield substantial benefits for malaria control in Brazil, aiding the country in achieving disease elimination and fulfilling the Sustainable Development Goals.


Assuntos
Malária , Brasil/epidemiologia , Malária/prevenção & controle , Malária/epidemiologia , Humanos , Notificação de Doenças/estatística & dados numéricos , Notificação de Doenças/métodos , Erradicação de Doenças/estatística & dados numéricos , Erradicação de Doenças/métodos , Monitoramento Epidemiológico , Sistemas de Informação em Saúde/estatística & dados numéricos
6.
An Acad Bras Cienc ; 96(2): e20231336, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38747801

RESUMO

The disease coronavirus COVID-19 has been the cause of millions of deaths worldwide. Among the proteins of SARS-CoV-2, non-structural protein 12 (NSP12) plays a key role during COVID infection and is part of the RNA-dependent RNA polymerase complex. The monitoring of NSP12 polymorphisms is extremely important for the design of new antiviral drugs and monitoring of viral evolution. This study analyzed the NSP12 mutations detected in circulating SARS-CoV-2 during the years 2020 to 2022 in the population of the city of Manaus, Amazonas, Brazil. The most frequent mutations found were P323L and G671S. Reports in the literature indicate that these mutations are related to transmissibility efficiency, which may have contributed to the extremely high numbers of cases in this location. In addition, two mutations described here (E796D and R914K) are close and have RMSD that is similar to the mutations M794V and N911K, which have been described in the literature as influential on the performance of the NSP12 enzyme. These data demonstrate the need to monitor the emergence of new mutations in NSP12 in order to better understand their consequences for the treatments currently used and in the design of new drugs.


Assuntos
COVID-19 , RNA-Polimerase RNA-Dependente de Coronavírus , SARS-CoV-2 , Humanos , Brasil , Simulação por Computador , COVID-19/virologia , COVID-19/transmissão , Mutação/genética , SARS-CoV-2/genética , Proteínas não Estruturais Virais/genética , RNA-Polimerase RNA-Dependente de Coronavírus/genética , RNA-Polimerase RNA-Dependente de Coronavírus/metabolismo
7.
An Acad Bras Cienc ; 96(2): e20231208, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38747841

RESUMO

The enterotoxigenic Escherichia coli (ETEC) strain is one of the most frequent causative agents of childhood diarrhea and travelers' diarrhea in low-and middle-income countries. Among the virulence factors secreted by ETEC, the exoprotein EtpA has been described as an important. In the present study, a new detection tool for enterotoxigenic E. coli bacteria using the EtpA protein was developed. Initially, antigenic sequences of the EtpA protein were selected via in silico prediction. A chimeric recombinant protein, corresponding to the selected regions, was expressed in an E. coli host, purified and used for the immunization of mice. The specific recognition of anti-EtpA IgG antibodies generated was evaluated using flow cytometry. The tests demonstrated that the antibodiesdeveloped were able to recognize the native EtpA protein. By coupling these antibodies to magnetic beads for the capture and detection of ETEC isolates, cytometric analyses showed an increase in sensitivity, specificity and the effectiveness of the method of separation and detection of these pathogens. This is the first report of the use of this methodology for ETEC separation. Future trials may indicate their potential use for isolating these and other pathogens in clinical samples, thus accelerating the diagnosis and treatment of diseases.


Assuntos
Anticorpos Antibacterianos , Escherichia coli Enterotoxigênica , Proteínas de Escherichia coli , Citometria de Fluxo , Animais , Feminino , Camundongos , Anticorpos Antibacterianos/imunologia , Escherichia coli Enterotoxigênica/imunologia , Proteínas de Escherichia coli/imunologia , Citometria de Fluxo/métodos , Imunoglobulina G/imunologia , Camundongos Endogâmicos BALB C , Sensibilidade e Especificidade , Adesinas Bacterianas/imunologia
8.
Malariaworld J ; 15: 8, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38737169

RESUMO

Plasmodium vivax causes the vast majority of malaria cases in Brazil. The lifecycle of this parasite includes a latent stage in the liver, the hypnozoite. Reactivation of hypnozoites induces repeated relapses. We report a case of two relapses of vivax malaria in a teenage girl after conventional treatment with chloroquine and primaquine. Chloroquine prophylactic treatment for three months was prescribed with a favourable outcome of the case.

9.
PeerJ ; 12: e17355, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38708361

RESUMO

Three new species of the Microlaimus genus (Nematoda: Microlaimidae) are described from sample sediments collected in the South Atlantic, along the Continental Shelf break of Northeastern Brazil. Microlaimus paraundulatus sp. n. possesses four setiform cephalic sensillae, a buccal cavity with three small teeth, arched and slender spicules and a wave-shaped gubernaculum. Microlaimus modestus sp. n. is characterized by four small cephalic sensillae, a buccal cavity with three teeth (one large dorsal tooth), cephalated spicules and a strongly arched gubernaculum in the distal region. Microlaimus nordestinus sp. n. is characterized by the following set of features: relatively long body, eight rows of hypodermal glands that extend longitudinally along the body and a funnel-shaped gubernaculum surrounding the spicules at the distal end. An amendment of the diagnosis is proposed for the genus.


Assuntos
Sedimentos Geológicos , Animais , Brasil , Oceano Atlântico , Sedimentos Geológicos/parasitologia , Masculino , Nematoides/classificação , Nematoides/anatomia & histologia , Nematoides/isolamento & purificação , Feminino
10.
Reprod Domest Anim ; 59(5): e14573, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38712666

RESUMO

The aim of this study was to assess the addition of 2% sodium caseinate in a commercial egg yolk-based medium in frozen ovine semen. Eight Dorper males were used for the study. The ejaculate was divided into two portions and frozen without (G1) or with the addition of 2% sodium caseinate (G2). Kinetic parameters were evaluated using CASA (computer-assisted sperm analysis), and membrane and acrosome integrity as well as oxidative stress were assessed using flow cytometry. After thawing, a thermoresistance test was conducted at time points T0 and T90. For the fertility test, 100 ewes were inseminated with semen from two rams selected based on in vitro parameters, one with good post-thaw quality (+70% total motility) and the other with low post-thaw quality (-55% total motility). For the fertility test, the females were divided into 4 groups for insemination: low-quality ram without caseinate (GBS = 25) and with caseinate (GBC = 25), and high-quality ram without caseinate (GAS = 25) and with caseinate (GAC = 25). Regarding the results of sperm kinetics, there was a statistically significant difference in the parameters of average path velocity (VAP) and curvilinear velocity (VCL) between the group frozen with BotuBov and the group with added caseinate. At time point T90, straight-line velocity maintained a trend (p < .06), with BotuBov® (BB group) being superior to caseinate this time, and in the linearity parameter, caseinate was superior to BotuBov®. Flow cytometry analysis showed no difference between any of the evaluated tests. In the fertility test, there was no statistically significant difference in the pregnancy rate between the BotuBOV® group (23%, 11/48) and the sodium caseinate group (BC group) (33%, 17/52), and no differences were observed in the male versus diluent interaction (p = .70). In conclusion, sodium caseinate supplementation did not influence sperm kinetic parameters and the fertility of sheep.


Assuntos
Caseínas , Criopreservação , Inseminação Artificial , Análise do Sêmen , Preservação do Sêmen , Motilidade dos Espermatozoides , Animais , Preservação do Sêmen/veterinária , Preservação do Sêmen/métodos , Masculino , Feminino , Criopreservação/veterinária , Criopreservação/métodos , Inseminação Artificial/veterinária , Caseínas/farmacologia , Análise do Sêmen/veterinária , Gravidez , Motilidade dos Espermatozoides/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Espermatozoides/fisiologia , Crioprotetores/farmacologia , Sêmen/efeitos dos fármacos , Fertilidade/efeitos dos fármacos , Ovinos , Carneiro Doméstico
11.
Parasit Vectors ; 17(1): 129, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38486221

RESUMO

BACKGROUND: Rhipicephalus (Boophilus) microplus is the most important tick species affecting cattle in the world. Under field conditions, the non-parasitic phase of R. (B.) microplus is unknown in the Amazon biome, including Brazil. The present study aimed to evaluate the non-parasitic phase of R. (B.) microplus in field (grass plots) and laboratory conditions. METHODS: The study was conducted from September 2020 to April 2022 in an Amazonian region (Maranhão State, Brazil). We evaluated the biological parameters of R. (B.) microplus under laboratory and field conditions. Engorged females were exposed to experimental conditions every 14 days, totaling 20 months of study. The following biological parameters were observed: pre-oviposition period, egg mass incubation period, and maximum larval survival period. RESULTS: Abiotic data (e.g., temperature and humidity) varied little throughout the year. Precipitation was the factor that varied the most throughout the year (dry ~ 30 mm3 and rain 400 mm3), and the parameters of pre-oviposition and pre-hatching are longer during the rainy season. A possible negative effect of the dry season on the percentage of hatched eggs was observed. Larval longevity in the plots of both control and free females was short (mean ~ 50-60 days), below that recorded for larvae under controlled conditions (mean ~ 95 days). CONCLUSIONS: Rhipicephalus (Boophilus) microplus was able to complete its non-parasitic phase by producing host-seeking larvae in the pasture during all months of the study. The results indicate that R. (B.) microplus can complete up to six generations per year in biome Amazon. To our knowledge, this is the highest number of annual generations for R. (B.) microplus in Latin America.


Assuntos
Rhipicephalus , Feminino , Animais , Óvulo , Estações do Ano , Larva , Biologia
12.
Magn Reson Med ; 92(2): 836-852, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38502108

RESUMO

PURPOSE: Arterial spin labeling (ASL) is a widely used contrast-free MRI method for assessing cerebral blood flow (CBF). Despite the generally adopted ASL acquisition guidelines, there is still wide variability in ASL analysis. We explored this variability through the ISMRM-OSIPI ASL-MRI Challenge, aiming to establish best practices for more reproducible ASL analysis. METHODS: Eight teams analyzed the challenge data, which included a high-resolution T1-weighted anatomical image and 10 pseudo-continuous ASL datasets simulated using a digital reference object to generate ground-truth CBF values in normal and pathological states. We compared the accuracy of CBF quantification from each team's analysis to the ground truth across all voxels and within predefined brain regions. Reproducibility of CBF across analysis pipelines was assessed using the intra-class correlation coefficient (ICC), limits of agreement (LOA), and replicability of generating similar CBF estimates from different processing approaches. RESULTS: Absolute errors in CBF estimates compared to ground-truth synthetic data ranged from 18.36 to 48.12 mL/100 g/min. Realistic motion incorporated into three datasets produced the largest absolute error and variability between teams, with the least agreement (ICC and LOA) with ground-truth results. Fifty percent of the submissions were replicated, and one produced three times larger CBF errors (46.59 mL/100 g/min) compared to submitted results. CONCLUSIONS: Variability in CBF measurements, influenced by differences in image processing, especially to compensate for motion, highlights the significance of standardizing ASL analysis workflows. We provide a recommendation for ASL processing based on top-performing approaches as a step toward ASL standardization.


Assuntos
Encéfalo , Circulação Cerebrovascular , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Marcadores de Spin , Humanos , Circulação Cerebrovascular/fisiologia , Reprodutibilidade dos Testes , Encéfalo/diagnóstico por imagem , Encéfalo/irrigação sanguínea , Processamento de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Imagem de Perfusão/métodos , Masculino , Feminino , Adulto , Algoritmos
13.
An Acad Bras Cienc ; 95(suppl 2): e20230061, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38198398

RESUMO

Cyanotoxins pose a health threat when present in the drinking water supply since conventional water treatment processes are not effective in removing extracellular metabolites hence, advanced treatment techniques are usually applied. Powdered activated carbon (PAC) is an effective adsorbent for removing toxins. However, since a high volume is necessary, alternative adsorbents have been investigated. Biochar, especially from renewable sources, is a potential adsorbent material that could replace PAC for removing toxins. This paper aimed to investigate which PAC properties play key roles in cyanotoxin adsorption by a systematic review addressing the adsorption of toxins such as microcystins-LR (MC-LR), cylindrospermopsin (CYL), and saxitoxins (STXs). As a result, the review showed that some commonly adopted indices (i.e. total surface area) are not relevant to cyanotoxin adsorption, especially if appraised alone. Along with a multi-barrier approach, PAC has to be applied taking into account the complexity of the water system, which includes a better understanding of the characteristics of the adsorbent, the target toxin, and the aqueous medium. The biochar systematic review showed that no studies have yet been designed specifically for the removal of toxins. Since biochar has not yet been applied to water treatment processes, the knowledge gap is even greater than for PAC.


Assuntos
Carvão Vegetal , Toxinas de Cianobactérias , Adsorção , Conhecimento , Pós
14.
N Engl J Med ; 390(5): 397-408, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38294972

RESUMO

BACKGROUND: Butantan-Dengue Vaccine (Butantan-DV) is an investigational, single-dose, live, attenuated, tetravalent vaccine against dengue disease, but data on its overall efficacy are needed. METHODS: In an ongoing phase 3, double-blind trial in Brazil, we randomly assigned participants to receive Butantan-DV or placebo, with stratification according to age (2 to 6 years, 7 to 17 years, and 18 to 59 years); 5 years of follow-up is planned. The objectives of the trial were to evaluate overall vaccine efficacy against symptomatic, virologically confirmed dengue of any serotype occurring more than 28 days after vaccination (the primary efficacy end point), regardless of serostatus at baseline, and to describe safety up to day 21 (the primary safety end point). Here, vaccine efficacy was assessed on the basis of 2 years of follow-up for each participant, and safety as solicited vaccine-related adverse events reported up to day 21 after injection. Key secondary objectives were to assess vaccine efficacy among participants according to dengue serostatus at baseline and according to the dengue viral serotype; efficacy according to age was also assessed. RESULTS: Over a 3-year enrollment period, 16,235 participants received either Butantan-DV (10,259 participants) or placebo (5976 participants). The overall 2-year vaccine efficacy was 79.6% (95% confidence interval [CI], 70.0 to 86.3) - 73.6% (95% CI, 57.6 to 83.7) among participants with no evidence of previous dengue exposure and 89.2% (95% CI, 77.6 to 95.6) among those with a history of exposure. Vaccine efficacy was 80.1% (95% CI, 66.0 to 88.4) among participants 2 to 6 years of age, 77.8% (95% CI, 55.6 to 89.6) among those 7 to 17 years of age, and 90.0% (95% CI, 68.2 to 97.5) among those 18 to 59 years of age. Efficacy against DENV-1 was 89.5% (95% CI, 78.7 to 95.0) and against DENV-2 was 69.6% (95% CI, 50.8 to 81.5). DENV-3 and DENV-4 were not detected during the follow-up period. Solicited systemic vaccine- or placebo-related adverse events within 21 days after injection were more common with Butantan-DV than with placebo (58.3% of participants, vs. 45.6%). CONCLUSIONS: A single dose of Butantan-DV prevented symptomatic DENV-1 and DENV-2, regardless of dengue serostatus at baseline, through 2 years of follow-up. (Funded by Instituto Butantan and others; DEN-03-IB ClinicalTrials.gov number, NCT02406729, and WHO ICTRP number, U1111-1168-8679.).


Assuntos
Vacinas contra Dengue , Vírus da Dengue , Dengue , Vacinas Atenuadas , Adulto , Criança , Pré-Escolar , Humanos , Anticorpos Antivirais , Dengue/prevenção & controle , Vacinas contra Dengue/efeitos adversos , Vacinas contra Dengue/uso terapêutico , Vírus da Dengue/imunologia , Método Duplo-Cego , Vacinação , Vacinas , Vacinas Atenuadas/efeitos adversos , Vacinas Atenuadas/uso terapêutico , Brasil , Eficácia de Vacinas , Adolescente , Adulto Jovem , Pessoa de Meia-Idade , Seguimentos
15.
eNeuro ; 11(2)2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38272676

RESUMO

Estimating durations between hundreds of milliseconds and seconds is essential for several daily tasks. Explicit timing tasks, which require participants to estimate durations to make a comparison (time for perception) or to reproduce them (time for action), are often used to investigate psychological and neural timing mechanisms. Recent studies have proposed that mechanisms may depend on specific task requirements. In this study, we conducted electroencephalogram (EEG) recordings on human participants as they estimated intervals in different task contexts to investigate the extent to which timing mechanisms depend on the nature of the task. We compared the neural processing of identical visual reference stimuli in two different tasks, in which stimulus durations were either perceptually compared or motorically reproduced in separate experimental blocks. Using multivariate pattern analyses, we could successfully decode the duration and the task of reference stimuli. We found evidence for both overlapping timing mechanisms across tasks as well as recruitment of task-dependent processes for comparing intervals for different purposes. Our findings suggest both core and specialized timing functions are recruited to support explicit timing tasks.


Assuntos
Percepção do Tempo , Humanos , Percepção do Tempo/fisiologia , Eletroencefalografia
16.
PLOS Glob Public Health ; 4(1): e0002845, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38295141

RESUMO

In Brazil, 99% of malaria cases occur in the Amazon region, mainly caused by Plasmodium vivax (~83%) and Plasmodium falciparum (Pf) species. Aligned with the Sustainable Development Goals, Brazil aims to eliminate autochthonous malaria by 2035. This study aims to analyse epidemiological patterns of malaria in Brazil to discuss if Brazil is on track to meet malaria control targets. A time-series study was conducted analysing autochthonous malaria new infections notifications in the Brazilian Amazon region from 2011 until June 2023. Descriptive analyses were conducted, along with joinpoint regression and forecast models to verify trend and future behaviour. A total of 2,067,030 malaria cases were reported in the period. Trend analysis indicated a decreasing trend in all malaria infections since late 2017 (monthly reduction = 0.81%, p-value <0.05), while Pf infections have increased progressively since 2015 (monthly increase = 0.46%, p-value <0.05). Forecast models predict over 124,000 malaria cases in 2023 and over 96,000 cases in 2024. Predictions for Pf infections are around 23,900 cases in 2023 and 22,300 in 2024. Cases in indigenous population villages are predicted to reach 48,000 cases in 2023 and over 51,000 in 2024. In gold mining areas it is expected over 21,000 cases in 2023 and over 20.000 in 2024. Malaria elimination in Brazil has advanced over the last decade, but its speed has slowed. The country exhibits noteworthy advancements in the reduction of overall malaria cases. It is imperative, however, to proactively target specific issues such as the incidence raise among indigenous populations and in gold mining areas. Pf infections remain a persistent challenge to control in the country and may require novel measures for containment. Current government supporting actions towards combating illegal goldmining activities and protecting indigenous populations may help malaria control indicators for the following years.

17.
Glia ; 72(3): 546-567, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37987116

RESUMO

Although brain scars in adults have been extensively studied, there is less data available regarding scar formation during the neonatal period, and the involvement of peripheral immune cells in this process remains unexplored in neonates. Using a murine model of neonatal hypoxic-ischemic encephalopathy (HIE) and confocal microscopy, we characterized the scarring process and examined the recruitment of peripheral immune cells to cortical and hippocampal scars for up to 1 year post-insult. Regional differences in scar formation were observed, including the presence of reticular fibrotic networks in the cortex and perivascular fibrosis in the hippocampus. We identified chemokines with chronically elevated levels in both regions and demonstrated, through a parabiosis-based strategy, the recruitment of lymphocytes, neutrophils, and monocyte-derived macrophages to the scars several weeks after the neonatal insult. After 1 year, however, neutrophils and lymphocytes were absent from the scars. Our data indicate that peripheral immune cells are transient components of HIE-induced brain scars, opening up new possibilities for late therapeutic interventions.


Assuntos
Cicatriz , Hipóxia-Isquemia Encefálica , Adulto , Animais , Humanos , Camundongos , Cicatriz/patologia , Encéfalo/patologia , Macrófagos , Hipóxia-Isquemia Encefálica/patologia
18.
Trop Med Infect Dis ; 8(12)2023 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-38133451

RESUMO

OBJECTIVE: The objective is to describe the results and the methodological processes of record linkage for matching deaths and malaria cases. METHODS: A descriptive cross-sectional study was conducted with probabilistic record linkage of death and malaria cases data in Brazil from 2011 to 2020 using death records from the Mortality Information System (SIM) and epidemiological data from the Notifiable Diseases Information System (Sinan) and Epidemiological Surveillance Information Systems for malaria (Sivep-Malaria). Three matching keys were used: patient's name, date of birth, and mother's name, with an analysis of cosine and Levenshtein dissimilarity measures. RESULTS: A total of 490 malaria deaths were recorded in Brazil between 2011 and 2020. The record linkage resulted in the pairing of 216 deaths (44.0%). Pairings where all three matching keys were identical accounted for 30.1% of the total matched deaths, 39.4% of the matched deaths had two identical variables, and 30.5% had only one of the three key variables identical. The distribution of the variables of the matched deaths (216) was similar to the distribution of all recorded deaths (490). Out of the 216 matched deaths, 80 (37.0%) had poorly specified causes of death in the SIM. CONCLUSIONS: The record linkage allowed for the detailing of the data with additional information from other epidemiological systems. Record linkage enables data linkage between information systems that lack interoperability and is an extremely useful tool for refining health situation analyses and improving malaria death surveillance in Brazil.

19.
An Acad Bras Cienc ; 95(suppl 3): e20230181, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38126379

RESUMO

This work aimed to characterize the variation in the thermal regime of the active layer in a permafrost area on Fildes Peninsula, Antarctica, and relate this variability with meteorological data between 2014 and 2016. The monitoring site was installed to continuously monitor the temperature and moisture of the active layer, radiation flow on the surface, and air temperature. We used data collected to generate the indexes freezing degree-days, thawing degree-days, frost number, n-factor, apparent thermal diffusivity, and active layer thickness. The temperature of the active layer is not homogeneous, varying with depth and position in the transect, with the greatest variations in soil with better drainage and lower moisture content. Among the evaluated factors, air and soil surface temperature are the ones that most influence the thermal gradient of the active layer. We identified that near the surface there is a greater influence of albedo and cloudiness and at -35 cm depth there is a greater influence of net radiation and soil moisture. The average depth of the active layer in 2014 was -44.3 cm and in 2015 -47.7 cm and the frost number index indicates that there was a predominance of continuous permafrost in the transect during the monitoring.


Assuntos
Monitoramento Ambiental , Poluentes do Solo , Regiões Antárticas , Solo , Congelamento , Poluentes do Solo/análise
20.
An Acad Bras Cienc ; 95(suppl 2): e20230519, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38126525

RESUMO

Monogeneans are a diverse group of flatworms, being ectoparasites of marine and freshwater fish, with great morphological and ecological variety. Analyzes of monogenetics in fish with great habitat diversity such as snappers are scarce in the literature, which already emphasizes the need for an update in this regard. The presente study found, morphologically characterized and mapped the geographic distribution and in known hosts the species Microcotyloides incisa and Microcotyloides impudicus, describing the first occurrence of these monogeneans for South America and in new hosts. The survey of hosts in the literature shows that M. incisa seems to have a greater Affinity with congener species of Lutjanidae and fish from other families, which may indicate a preference or specificity for fish of this family because they are congeners of their host type. The introduction of these parasites into South American waters may have occurred due to the migratory behavior of snappers, which are well distributed along the Mexican coast, where the parasites are usually reported. Here, we also bring the first occurrence of M. incisa for Lutjanus analis and Lutjanus jocu and M. impudicus for Ocyurus chrysurus and Lutjanus synagris, helping in the mapping and distribution of these monogenetic species in the Americas.


Assuntos
Doenças dos Peixes , Parasitos , Perciformes , Platelmintos , Trematódeos , Humanos , Animais , Brasil , Peixes , Perciformes/parasitologia , Doenças dos Peixes/parasitologia
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