Memorias do Instituto Oswaldo Cruz最新文献

Background: Acanthamoebae are causative agents of severe and complicated human infections without a standard effective therapy to date. Therefore, the research is focused on the development of new amoebicidal drugs based on the natural products. Plants of the family Lamiaceae are typical with several phenolic secondary metabolites that make them interesting in medical point of view.

Objective: In this review, we concentrate on anti-Acanthamoeba activities of plant extracts, essential oils, and phytochemicals of Lamiaceae in the published literature.

Findings: A total of 13 articles in the research field were found. Totally, 16 plant species belonging to family Lamiaceae were studied against trophozoites and cysts of Acanthamoeba in in vitro conditions. Low toxicity of the Lamiaceae plant extracts to tissue cultures enhances their possible potential for clinical use. The research demonstrated promising trophocidal and cysticidal effects against acanthamoebae. Further research is needed with inclusion of more clinical isolates and in vivo studies.

Main conclusion: Reviewing the related literature highlights the promising amoebicidal activities of plant extracts, essential oils and bioactive compounds of family Lamiaceae. Identifying the active components could lead to production new effective and well-tolerated drugs for the Acanthamoeba infections treatment.

Background: Rhodnius neivai, a kissing bug found in the dry regions of Colombia and Venezuela, has limited documented occurrences. While it is not deemed a significant vector for Chagas disease, distributional and ecological studies are essential in monitoring species domiciliation and shedding light on the evolutionary aspects of the Rhodniini tribe.

Objectives: The study aims to provide a detailed revision of R. neivai distribution and evaluate general spatial data quality for ecological niche modelling (ENM). It will also provide the first published ENM for the species, which may aid species sampling and future analytical improvement.

Methods: Registers and other spatial information were gathered by literature review; data georeferencing, preliminary geographical investigations, and model editing were conducted in GIS platforms; ENMs were built using R and explored the uncertainty of parameters and algorithms.

Findings: Twenty four unique sites were identified, unearthing 17 previously uncovered records. Data lacks robust spatial and temporal precision; however, ENMs had acceptable validations. The models present some variation in suitability but with objective areas for sampling effort.

Main conclusions: Rhodnius neivai distribution is better explained by conditions that characterise dry ecotypes, but further sampling is essential to improve modelling and advance with ecological and evolutive matters.

Background: Herpesviruses are common co-pathogens in individuals infected with human immunodeficiency virus (HIV). Herpes simplex virus type 1 (HSV1) enhances HIV-1 replication and has evolved mechanisms to evade or disrupt host innate immune responses, including interference with interferon (IFN) signalling pathways.

Objectives: The aimed of this work was evaluated whether it HSV1 affects HIV-1 replication through the modulation of the IFN pathway in human macrophages.

Methods: Co-infections with HSV1 and HIV-1 were performed in monocyte-derived human macrophages (hMDMs). The production of infectious HIV-1 and HSV-1 was monitored 48 h post-coinfection. Additionally, mRNA and protein expression levels of interferon-stimulated genes (ISGs) were evaluated in both HIV-1-HSV1 coinfections and HSV1 mono-infections.

Findings: The HSV1 coinfection increasing the HIV-1 productive replication, following of downregulation of interferon-alpha (IFN-α) and interferon-induced transmembrane protein 3 (IFITM3) expression in hMDMs. Acyclovir treatment, in a dose-dependent manner, mitigated HSV1's ability to decrease IFITM3 levels. Knockdown of HSV1 Us11 and virion host shutoff (VHS) genes reactivated the IFN pathway, evidenced by restored IFITM3 expression and activation of eIF2-α and PKR. This knockdown also returned HIV-1 replication to baseline levels.

Main conclusions: Our data suggested that HSV1 increases HIV-1 replication in human macrophages is associated with the downregulating interferon pathways and ISGs expression.

Background: Undifferentiated acute febrile illness (UAFI) cause by several pathogens poses a diagnostic challenge due to the similarity on the clinical manifestations across these diseases. Precise pathogen detection is vital for appropriate medical intervention, early treatment, and timely outbreak alerts regarding emerging pathogens. In tropical regions, UAFI is predominantly linked to a wide range of viral, bacterial, and parasitic infections. Hence, confirmatory laboratory tests are essential for specific pathogen identification.

Objectives: Our primary goal was to develop two real-time multiplex polymerase chain reaction (PCR) assays for simultaneous detection of six neglected pathogens (Leptospira spp., Rickettsia spp., Borrelia spp., Anaplasma spp., Brucella spp., and Bartonella spp.), known for causing UAFI in tropical regions.

Methods: We rigorously assessed assays parameters including: linearity, efficiency, sensitivity, and reproducibility in both singleplex and multiplex formats.

Findings: Our results demonstrated that these multiplex assays are reliable and sensitive methods. They showed good performance with low intra- and inter-variability (< 10%) and consistently high efficiencies (> 90%).

Main conclusions: These assays offer the alternative of streamlining work, reducing processing costs, and minimizing sample volume use. In conclusion, we present two dependable, user-friendly, rapid, and cost-effective methods for simultaneously detecting six neglected bacteria, as a significant laboratory tool in resource-limited tropical settings.

This perspective presents and supports arguments for a new formulation of epoxy-α-lapachone loaded microemulsion (ELAP-ME), a nanosystem, as a prototype drug for the treatment of leishmaniasis. The benefits of ELAP as a multitarget compound, with properties that affect key physiological pathways of Leishmania spp. are discussed. ELAP-ME demonstrated efficacy in murine infection models, particularly with the binomial BALB/c-Leishmania (Leishmania) amazonensis. Furthermore, it is proposed that the technological maturity of ELAP-ME be classified as Technology Readiness Level 4 (TLR 4) within the context of innovative drugs for American Cutaneous Leishmaniasis (ACL).

Chagas disease (CD), caused by Trypanosoma cruzi, is a life-threatening neglected anthropozoonosis primarily transmitted by triatomine bugs. Affecting an estimated 5.7 million people globally, CD has significant morbidity and mortality, particularly in Latin America. The Oxente Chagas Bahia Project aims to screen approximately 30,000 individuals, validate a rapid diagnostic test in a real-world setting, and provide crucial data on its diagnostic performance and cost-effectiveness. Additionally, a biobank will be established to support further research on disease biomarkers and treatment cure rates. By enhancing access to timely diagnosis and treatment, the project will evaluate a strategy to reduce the CD burden.

Background: Corynebacterium auriscanis is a bacterial species frequently isolated from dogs with external otitis or dermatitis and a zoonotic pathogen transmitted by dog bite. It is considered an opportunistic pathogen, but its pathogenicity mechanisms are poorly studied. Comparative genomics can identify virulence and niche factors that could contribute to understanding its lifestyle.

Objectives: The objectives of this project was to compare genomes of C. auriscanis to identify genes related to its virulence and lifestyle.

Methods: The genome of strain 32 was sequenced using Illumina HiSeq 2500 (Illumina, CA, USA) and assembled using Unicycler. The two other non-redundant genomes from the same species available in GenBank were included in the analysis. All genomes were annotated and checked for taxonomy, assembly quality, mobile elements, CRISPR-Cas systems, and virulence and antimicrobial resistance genes. The virulence genes in the three genomes were compared to the ones from other pathogens commonly isolated with C. auriscanis.

Findings: The species has 42 virulence factors that can be classified as niche factors, due to the absence of true virulence factors found in primary pathogens. The gene rbpA could confer basal levels of resistance to rifampin.

Main conclusions: The absence of true virulence factors in the three genomes suggests C. auriscanis has an opportunistic pathogen lifestyle.

Background: The Golden Syrian hamster (Mesocricetus auratus), Ferrets (Mustela putorius furo), and macaques have been described as useful laboratory animals naturally susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

Objectives: To study the mechanism of lung injury, we describe the histopathological features of SARS-CoV-2 infection in Golden Syrian hamsters inoculated intranasally with the A.2 Brazilian strain.

Methods: Hamsters were intranasally inoculated with the A.2 variant and euthanised at 3-, 5-, 10- and 15-days post-inoculation. The physical examination and body weight were recorded daily. Neutralising antibodies and viral RNA load of the respiratory tract were assessed during necropsies.

Findings: The coronavirus disease 2019 (COVID-19) model presented body weight loss, high levels of respiratory viral RNA load, severe segmentary pneumonitis, and bronchial fistula besides lymphatic trapping and infiltration, like the human SARS-COV-2 pathogenesis. The presence of subepithelial lymphoeosinophilic infiltrate was highlighted in our results; it contributed to the detachment of SARS-CoV-2 nucleocapsid-positive epithelial cells resulting in the infectious cell plugs.

Main conclusions: The SARS-CoV-2 caused segmentary pneumonia and vascular damage. In our comprehension, the infectious cell plugs, as being aspirated from the upper respiratory tract into the terminal bronchial lumen, work as a "Trojan horse", thus contributing to the dissemination of the SARS-CoV-2 infection into specific regions of the deep lung parenchyma.

Background: The presence of Aedes albopictus in Bolivia has been a subject of controversy, with a lack of concrete documentation.

Objectives: This study aimed to provide evidence of Ae. albopictus presence in Bolivia.

Methods: Larval habitats were sampled in Rosario del Yata and San Agustín, Guayaramerín Municipality, Beni Department, northern Bolivia. Collected mosquito larvae were reared to the L4 and adult stages for morphological identification, with some specimens sequenced for confirmation.

Findings: Aedes albopictus was identified in multiple larval habitats within peridomestic areas, such as buckets, canisters, and cut plastic bottles used as flower vases in both localities, confirming its establishment in the area. This represents the first concrete documentation of the species in Bolivia. The collections (larvae and adults) have been deposited in the Medical Entomology Laboratory of the Universidad Mayor de San Simón in Cochabamba, Bolivia, and the Laboratory of Entomology of the Instituto Nacional de Laboratorios de Salud of the Ministry of Health in La Paz, Bolivia.

Main conclusion: Given its role as a vector for arboviruses such as dengue and Chikungunya, Ae. albopictus should be incorporated into the Bolivian National Programme of Vector Control for monitoring.

Background: Echinococcosis and schistosomiasis, caused by parasitic worms, pose significant threats to millions of people in the world. Rapid and effective pathogen detection and epidemic control by public health authorities are urgently needed.

Objectives: In this study, we aimed to develop rapid on-site detection method to detect echinococcosis and schistosomiasis.

Methods: Recombinase polymerase amplification (RPA) was utilised to examine its efficacy of detection of echinococcosis and schistosomiasis.

Findings: The detection probes for RPA were created through comparing parasitic genomes from international genomic data and the sequences generated by our group. We established an optimised RPA on-site testing platform, which significantly reduces the detection time (less than 30 min) and simplifies the operation (free of expensive equipment) as compared to traditional polymerase chain reaction (PCR) method.

Main conclusions: This RPA detection platform in our study for identifying echinococcosis or schistosomiasis pathogens would be greatly applicable for epidemic investigation, border screening, and early clinical diagnosis.