Memorias do Instituto Oswaldo Cruz最新文献

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.

Free-living amoebas (FLA) are ubiquitous protists found in the environment. They have shown exceptional resistance to environmental challenges and play significant roles in controlling microbial populations through their predatory behaviour and microbicidal activity in both soil and aquatic ecosystems environments. However, although rare, a limited group of FLA can cause serious infections in the central nervous system and other diseases, particularly in immunocompromised individuals with high mortality rates. They can also cause keratitis in otherwise healthy individuals. This review offers a comprehensive overview of freshwater naked amoebae but does not cover all aspects in detail. Its goal is to provide a historical context for our current understanding while addressing the most critical elements of FLA biology, their pathogenic potential, and their interactions with important human pathogens.

Background: Chagas disease (CD) is a neglected tropical disease caused by Trypanosoma cruzi. The current drugs used to treat these diseases have limited efficacy and produce severe side effects. 4-aminoquinoline derivatives were shown to be a promising class of inhibitors of cysteine proteases cruzain and TbrCATL.

Objectives: To evaluate the trypanocidal activity of a new series of aminoquinolines as potential inhibitors of cruzain and TbrCATL.

Methods: Three aminoquinolines were synthesised and their in vitro activity was evaluated against cruzain and TbrCATL as well as against amastigotes and trypomastigotes forms of T. cruzi. In silico studies were also carried out to try to understand the experimental results.

Findings: Compound 5 showed promising activity against cruzain and TbrCATL, with better performance than E60, the reference drug. Compound 5 inhibited cruzain and TbrCATL at IC50 of 23 µM ±3 and 29 µM ±1, respectively, but this inhibition showed characteristics of promiscuous inhibition by colloidal aggregation. On the other hand, the compound 4 showed to be more promising activity against T. cruzi with IC50 2.57 µM ± 0.03 lower than the reference drug benznidazole 3.8 µM.

Main conclusions: The results of this study can guide new drug development for the treatment of trypanosomiasis.

Background: The neglected illness Chagas disease is treated with limited efficacy and adverse effects by old drugs. Due to the low interest of pharmaceutical industry in targeting economically depressed-patients, repurposing is a tool that should be applied because it can introduce new anti-Chagas entities into the clinic at reduced costs.

Objectives: To investigate the repurposing/combination of medicines strategies as anti-Chagas treatment.

Methods: Epimastigotes, trypomastigotes and amastigotes of Trypanosoma cruzi were in vitro exposed to 28 Uruguayan-approved medicines not previously tested, 28 FDA-approved medicines previously evaluated, and three reference agents. Parasite inhibition was assessed and for the best drugs, in pairs-isobolographic studies, looking for synergism/additivity/antagonism, were done. Macrophages were used to study selectivity. For some relevant agents, we analysed whether medicines mammals´ action mechanisms are operative in epimastigotes-T. cruzi.

Findings: From the anti-epimastigotes monotherapy-screening, we found that 18% of them showed better/comparable activities than references. Additionally, for the binary-combinations 8% were additive, 4% were synergic and the rest showed antagonism. Favourably, in macrophages-cytotoxicity four of the binary-combinations were antagonists. Naftazone and pinaverium bromide, not previously tested against T. cruzi, maintained their activity against trypomastigotes and amastigotes. The identified action mechanisms open the door to new strategies designing anti-T. cruzi drugs.

Main conclusions: Using approved-medicines is a good strategy for new anti-Chagas treatments.

Background: The nematode Angiostrongylus cantonensis, which is endemic to Southeast Asia and adjacent Pacific Islands, has already been recorded in more than 30 countries, including Brazil and other South American nations. It is one of the principal etiological agents of the zoonosis Eosinophilic Meningitis (EoM), which has a number of different species of terrestrial gastropods that act as its intermediate hosts.

Objective: The present study investigated the occurrence of the larvae of this nematode in specimens of terrestrial molluscs collected in half of the municipalities of the Brazilian State of Rio de Janeiro.

Methods: The study is based on the surveillance of this nematode in the Brazilian State of Rio de Janeiro, where terrestrial snails and slugs were collected in more than half of the state's municipalities (46 in all), and examined for parasitological infections. The nematode larvae retrieved from these specimens were identified based on their morphology and cytochrome oxidase I (COI) mitochondrial DNA sequences.

Findings: Angiostrongylid larvae were found in 230 (8.8%) of the 2,600 terrestrial molluscs examined, collected from 26 municipalities. Overall, 14 terrestrial gastropod species were identified, including both native and exotic taxa, and six were found to be infected naturally by A. cantonensis. The natural infection rates by Angiostrongylus in the different terrestrial molluscs species were 12.5% in Angustipes erinaceus, 9.7% in Achatina fulica, 6.8% in Bradybaena similaris, 6.3% in Sarasinula linguaeformis, 3.9% in Leptinaria unilamellata, and 4.6% in Subulina octona. A. fulica was the most frequent and extensively distributed species, with infected snails being found in 22 municipalities.

Main conclusions: The data from this first comprehensive survey of A. cantonensis in Rio de Janeiro highlights the potential epidemiological risk of human infection in this state. Mapping the spread of infected molluscs will also provide essential information for the evaluation of the risk of human infection, and should help local health authorities to provide a faster and more accurate diagnosis whenever neuroangiostrongyliasis is suspected.

Background: Non-O1 and non-O139 Vibrio cholerae (NOVC) that cause bacteraemia have attracted the attention of the public health community around the world, mainly due to the prospect of outbreaks and the way to treat such infections.

Objectives: To identify V. cholerae lineages and their antibiotic resistance and virulence factors associated with bacteraemia.

Methods: Vibrio cholerae genomes associated with strains isolated from blood were retrieved and subjected to core genome-based phylogenomic analysis with Roary. The virulome and resistome were searched with abricate using the VFDB and CARD databases.

Findings: Analysis showed that, in addition to V. cholerae, Vibrio paracholerae also causes bacteraemia. The NOVC group was highly diverse, although genomes from different countries were related. Most bacteraemic Vibrios came from countries not affected by epidemic/endemic cholera. The NOVCs virulome presented factors, such as type III and VI secretion systems, HapA, HlyA, RTX, and TLH. Importantly, no resistance to third-generation cephalosporin has been identified in the resistome of NOVCs.

Main conclusions: The presence of multiple NOVC lineages that cause bacteraemia in different parts of the world shows that there is no geographic and socioeconomic restriction for these cases. Therefore, healthcare systems need to be aware of this uncommon but deadly Vibrio infection.

Malaria, caused by Plasmodium spp., remains a major public health problem. Cerebral malaria is its deadliest form, with a 15-25% mortality rate, despite artemisinin-based treatments. In addition, the World Health Organization (WHO) strictly defines cerebral malaria as the presence of coma, 1 h after a seizure or the correction of hypoglycemia, in patients with P. falciparum parasitemia. Consequently, 25% of survivors experience neurocognitive and behavioral sequelae, particularly in children. However, more recently, neurocognitive and behavioral impairments were also reported in severe non-cerebral malaria, non-severe malaria, and even during asymptomatic Plasmodium infection. Such impairments have been observed in school-aged children, the elderly, and in animal models without classic cerebral malaria pathology. Additionally, mild vasogenic edema has been detected in neuroimaging of patients with severe non-cerebral and non-severe P. falciparum malaria. Therefore, given that approximately 98% of malaria cases in the world are non-severe, neurocognitive and behavioral sequelae may account for a significant proportion of global malaria morbidity. Taken together, these observations suggest that systemic inflammation from malaria, even without traditional cerebral malaria signs, can disrupt brain function and lead to long-term sequelae. We propose that the current definition of cerebral malaria may not fully capture the observed evidence and a new conceptualization is necessary to encompass these findings.

Diphtheria, a severe respiratory infection, was a major killer of children until the early years of the 20th century. Although diphtheria is now largely controlled globally thanks to vaccination, it is still endemic in some world regions and large epidemics can occur where vaccination coverage is insufficient. The pathological effects caused by its main virulence factor, diphtheria toxin, can be diminished by passive transfer of antibodies. Equine diphtheria antitoxin (eDAT), the cornerstone of treatment against toxinic complications of diphtheria, was invented more than 130 years ago, in 1890, and is still in use today. A method to concentrate anti-diphtheria antibodies from hyperimmune equine serum was described in the first issue of Memórias do Instituto Oswaldo Cruz in 1909. On this historic occasion, we present recent knowledge on taxonomic, epidemiological and clinical aspects of diphtheria agents that produce diphtheria toxin, and provide a historical perspective on eDAT treatment, adverse effects, threats on its scarce international supply, and current avenues for alternative therapeutic strategies.