Memorias do Instituto Oswaldo Cruz最新文献

Background: Efflux pumps represents one of the most important mechanisms of antibiotic resistance. They allow bacteria to expel antibiotics from their cells before they reach the target site.

Objectives: The main objective of this work was to examine how cultivation temperature and its variations affect the activity of efflux pumps in Acinetobacter junii, Bacillus cereus, and Enterobacter cloacae isolated from a skin swab.

Methods: The isolation and purification of bacterial colonies were done through the streak plate method. For the identification of bacterial species, MALDI-TOF was utilised. To detect the activity of efflux pumps, agar-ethidium bromide cartwheel method was implemented.

Findings: The accumulation of ethidium bromide (EtBr) in bacterial cells was higher at 43ºC than at 30ºC, so the activity of efflux pumps was reduced at 43ºC in all isolates. A temperature of 7ºC also caused increased cumulation of EtBr in the cells, hence decreasing the activity of efflux pumps in isolated bacteria. Moreover, B. cereus was more sensitive to meropenem at 43ºC than at 36ºC.

Main conclusions: The activity of efflux pumps and antibiotic resistance can be strongly affected by changes in incubation temperature in vitro in tested human opportunistic bacterial pathogens.

Background: Toxocariasis is a neglected global zoonosis. The immunological diagnosis has setbacks that hinder further knowledge about its pathology, epidemiology, and public control measures, and lack of financial support and attention prevents innovative research. Although studies on synthetic peptides are common for several infectious pathologies, none evaluated chemically synthetic peptides for toxocariasis diagnosis.

Objective: This study aimed to identify potential synthetic peptides from C-type lectin 1 (Tc-CTL-1) from Toxocara canis.

Methods: In silico analyses were made by five B-cell peptide prediction programs, 3-D modelling, BLASTp homology analysis, and signal-peptide identification. SPOT-synthesis was used for epitope mapping and assessed by dot-blot. Sera from non-infected and T. canis, Strongyloides venezuelensis, Ascaris suum, or Schistosoma mansoni-infected animals were used to assess the peptide's immunogenicity and cross-reactivity. The selection of potential immunogenic epitopes included the most immunogenic peptides with the least cross-reactivity.

Findings: Fifty-five peptides were selected by in silico analysis. Dot-blot showed intense recognition by anti-Toxocara IgG and cross-reactivity with A. suum-infected mice. Selection criteria identified four epitopes with diagnostic potential.

Main conclusions: The findings demonstrate that synthetic peptides should be explored for innovation of toxocariasis diagnosis, and suggest the adaptation of dot-blot using the SPOT-synthesis technique as a potential immunodiagnostic platform.

Background: Bacillus Calmette-Guérin (BCG) is one of the most successful vaccines in the world and evidence suggests it can be used as a bacterial vector to deliver heterologous antigens.

Objectives: We evaluated whether BCG could be biotinylated and used as a carrier of Schistosoma mansoni antigen tetraspanin-2 (TSP-2) fused with rhizavidin, an avidin analog.

Methods: BCG was grown and biotinylated. The recombinant protein Rzv:TSP-2 was produced and purified from Escherichia coli. The biotinylation and antigen coupling was analysed by flow cytometry, enzyme-linked immunosorbent assay (ELISA) and Western blot. Vaccine immunogenicity was tested in immunised mice by the assessment of lung and splenic T cells.

Findings: BCG can be biotinylated, which in turn, can be coupled with Rzv:TSP-2. After a series of optimisations which involved molarity of the biotin, ratio of BCG:reagent and the concentration of Rzv:TSP-2 used, almost 50% of the bacteria were biotinylated and 35% coupled with antigen. Although a clear adjuvant effect of BCG was observed, evaluation of immune response in immunised mice demonstrated an overall low immunogenicity of the BCG-Rzv:TSP-2.

Main conclusion: These results demonstrated the use of BCG as a carrier of avidin-tagged antigens. Further optimisations are needed in order to strengthen the stability of tagged proteins in order to produce antigen-specific immune responses.

Background: Benznidazole (BNZ) is the primary treatment for Chagas disease. While pharmacokinetic studies of BNZ began in the 1970s, its metabolism and excretion are not fully understood. Alternatives like Benznidazol Lafepe® and Abarax® have replaced the original Radanil®.

Objectives: To compare the pharmacokinetic profiles of both currently available formulations of BNZ in adults with chronic Trypanosoma cruzi infection.

Methods: The study involved 13 subjects each one receiving 100 mg of both presentations one week apart. Blood samples were collected over 48 hours post-administration to analyse BNZ concentration and calculate pharmacokinetic parameters.

Findings: The analysis showed that both presentations had similar maximum plasma concentration and time to reach maximum plasma concentration values. Area under curve (AUC) values were slightly lower in Abarax® than Benznidazol Lafepe®. High intra-individual variability was observed, attributed to erratic absorption patterns with multiple peaks in concentration-time curves. The half-life values for both formulations were 9.1 and 8.0 h, respectively, with a significant intra-individual variability over 30%.

Main conclusions: The mean difference in the AUC was lower than 10%, but exceeded the 90% confidence interval for the higher bioequivalence limit. Despite the high variability that confirms erratic absorption, the pharmacokinetic parameters of both formulations were within expected ranges.

The 2015-16 Zika virus (ZIKV) epidemic has posed unprecedented concern for maternal-infant health, mainly due to the substantial risk of microcephaly and other neurological birth abnormalities associated with congenital ZIKV syndrome (CZS). As licenced vaccines and effective antivirals are still unavailable, attention has been focused on post-delivery in vitro or translational in vivo studies to understand the impact of maternal ZIKV infection on placentation and neurodevelopmental consequences for the foetus. Here, we review clinical and translational studies highlighting ZIKV-induced maternal-foetal interface dysfunction, adding to our previous observations of experimental ZIKV vertical transmission to pregnant rhesus monkeys and newly published post-epidemic findings about the theme. This comparative review focuses on the mechanisms by which the virus has a cytopathic effect on trophoblasts and macrophages during placentation in humans, nonhuman primates, and rodent transgenic models, crosses the placental barrier, replicates, and establishes a persistent uteroplacental infection. When considering the mechanism of ZIKV-induced birth defects in humans and other susceptible hosts, it becomes apparent how the various stages of the ZIKV cycle in the host (both the parent and offspring) unfold. This understanding presents specific opportunities for pharmacological intervention and the development of preventative vaccines.

Haemosporida research started in the 19th century with the description of Plasmodium and other related parasites infecting mammals and birds. Here, we highlight the pioneering contributions of Henrique Aragão and Arthur Neiva in describing the first two Plasmodium species in lizards from the New World, Plasmodium diploglossi and Plasmodium tropiduri, published in the first printed issue of Memórias do Instituto Oswaldo Cruz in April 1909. We use these discoveries as a background to explore some historical and taxonomic aspects of Plasmodium species infecting reptiles, with a particular emphasis on the advancements made over the past 115 years in the Neotropics. Our review underscores the complexities and persistent challenges in the taxonomic classification of reptile haemosporidians and discusses some scientific advances in the field that improved our understanding of the biology and evolution of these parasites.

Background: The works of Lutz & Neiva, published 115 years ago in the Memórias do Instituto Oswaldo Cruz, are pioneering for the study of Neotropical Tabanidae. These studies emphasised the importance of biological collections and the description of species from the exploration of South American areas. Dasybasis Macquart, 1847 has traditionally been considered a large genus of tabanids restricted to the Australasian, Neotropical, and Andean regions. Dasybasis species exhibit a high degree of morphological similarity, making specific differentiation challenging. Moreover, some of these features are also present in other taxa, suggesting that they may not be homologous characters and should not be used to define the genus.

Objectives: This study aimed to assess the monophyly of Dasybasis and establish its major monophyletic groups.

Methods: We conducted an implied weighting analysis using morphological characters, and wing landmarks from 91 terminal species.

Findings: For the total evidence analyses, aligning with either Tabanus Linnaeus or Dasybasis appendiculata Macquart yielded slightly different trees. Classical morphology and total evidence topology aligned with D. appendiculata are the same, while differing from the total evidence topology aligned with Tabanus in two nodes.

Main conclusions: Our results indicate that Dasybasis was not a monophyletic group, and that this name should be restricted to species with a distribution in Australasia; while Neotropical Dasybasis species are recovered in different clades. The genera Archiplatius, Pseudoselasoma, and Stypommia are revalidated. This study provides a revised phylogenetic framework for "Dasybasis" and related taxa, highlighting the need for a more nuanced understanding of morphological character evolution within the tribe Diachlorini.

The history of the plague, caused by Yersinia pestis, is marked by some of the most devastating pandemics. Its arrival in Brazil on the turn of the 19-20th century led to significant public health challenges and responses. Here, we discuss a comprehensive perspective on the history of the plague in Brazil, emphasising epidemiological trends, public health responses and scientific advances. Understanding the history of the plague in Brazil provides valuable insights into infectious disease control. The study highlights the importance of early detection, robust public health infrastructure, and ongoing research, emphasising the lasting influence of epidemic diseases on society.

In 1909, Arthur Neiva published an article titled "Contribuição para os estudos dos dipteros. Observação sobre a biolojia e sistematica das anofelinas brasileiras e suas relações com o impaludismo", highlighting the biology, ecology, and distribution of Anophelinae mosquitoes and the need for more taxonomic studies in Brazil. This came 11 years after Ronald Ross and Grassi demonstrated mosquito roles in transmitting Plasmodium to birds and humans. Despite considerable advances in the understanding of Anophelinae species, knowledge remains insufficient given the complexity of Brazil's ecosystems, the intensified anthropogenic environmental changes since the mid-20th century, and the persistent public health challenges posed by malaria. This perspective article presents the distribution of Plasmodium vectors and potential vector species in Brazil using climate variables and a maximum entropy model. Geographical distribution maps of Anophelinae species, including putative species, are provided. The article also discusses the current knowledge of vector species distribution in relation to Brazil's malaria elimination plan, along with the ecological and anthropogenic factors influencing vector distribution.