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Memorias Do Instituto Oswaldo Cruz[JOURNAL]

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Differential expression of peptidases in Strigomonas culicis wild-type and aposymbiotic strains: from proteomic data to proteolytic activity.

Santos JFBD, Bombaça ACS, Vitório BDS … +5 more , Dias-Lopes G, Garcia-Gomes ADS, Menna-Barreto RSF, d'Avila CM, Ennes-Vidal V

Mem Inst Oswaldo Cruz · 2024 · PMID 39661825 · Full text

BACKGROUND: Strigomonas culicis is a monoxenic trypanosomatid parasite of insects that naturally contains an endosymbiotic bacterium. The aposymbiotic strain can be obtained, making this strain a model for evolutive rese... BACKGROUND: Strigomonas culicis is a monoxenic trypanosomatid parasite of insects that naturally contains an endosymbiotic bacterium. The aposymbiotic strain can be obtained, making this strain a model for evolutive research about organelle origins. In addition, S. culicis contains homologues of virulence factors of pathogenic trypanosomatids, which functions are waiting for further analysis. In this sense, the publication of S. culicis proteome makes feasible additional investigations regarding the differential expression of peptidases from the wild-type (WT) and the aposymbiotic (APO) strains. OBJECTIVES: Here, we analysed two proteomic data from S. culicis WT and APO strains screening for peptidases differentially expressed and assessed the differential expression of cysteine and metallopeptidases. METHODS: A comparative proteomic screening between WT and APO identified 43 modulated peptidases. FINDINGS: Cysteine and metallopeptidases, such as calpains and GP63, were the major classes, highlighting their significance. GP63 exhibited an increased proteolysis in a specific metallopeptidase substrate, an up-modulation gene expression in RT-PCR, and a higher protein identification by flow cytometry in the aposymbiotic strain. Notwithstanding, the wild-type strain showed enhanced cysteine peptidase activity. MAIN CONCLUSION: Our study highlighted the endosymbiont influence in S. culicis peptidase expression, with GP63 expression and activity raised in the aposymbiotic strain, whereas cysteine peptidase levels were reduced.

Molecular test for screening malaria-infected blood donors to maximise recipient safety in Acre State, a Brazilian endemic area.

Pinheiro TCP, Santos SS, Simião FMEB … +7 more , Mello ARL, Pimentel CB, Lomonaco LA, Alvarez P, Daniel-Ribeiro CT, Koifman RJ, Ferreira-da-Cruz MF

Mem Inst Oswaldo Cruz · 2024 · PMID 39661824 · Full text

BACKGROUND: Although blood transfusion is an essential therapeutic procedure, it can present risks, including transmitting infectious diseases, such as malaria. In Acre, the thick blood smear microscopic examination (TBS... BACKGROUND: Although blood transfusion is an essential therapeutic procedure, it can present risks, including transmitting infectious diseases, such as malaria. In Acre, the thick blood smear microscopic examination (TBS) is used to screen infected malaria blood donors. However, TBS has low sensitivity for detecting Plasmodium in situations of low parasitaemia, such as those presented by asymptomatic clinically healthy individuals. OBJECTIVES: To investigate the pertinence of using polymerase chain reaction (PCR) to detect malarial infection for screening blood donors in Cruzeiro do Sul, Acre, an endemic high-risk malaria area in the Legal Amazon. METHODS: A cross-sectional study was conducted among individuals eligible and ineligible to be blood donors, according to clinical and epidemiological criteria. Besides the mandatory screening of HCV, HBV, and HIV tests, malaria PCR and TBS were also carried out on all blood donor candidates who attended the Cruzeiro do Sul Blood Centre from July to September 2022. FINDINGS: Of the 230 participants, 209 (91%) were eligible for blood donation by clinical-epidemiological screening. Surprisingly, no blood donor candidate reported a history of malaria. All TBS microscopic tests were negative at the time of recruitment. However, samples from four blood donor candidates (two eligible by clinical and epidemiological malaria criteria and two ineligible by hypertension and recent tattoo) were positive by Plasmodium and P. vivax molecular tests. MAIN CONCLUSIONS: Malaria molecular techniques for screening blood donors should be introduced in the Brazilian Blood Centres to maximise recipient safety. Furthermore, selecting zero-risk donors could pave the way to build a transmissible malaria-free environment in the blood bank context in the near future.

Revisiting the development of Trypanosoma rangeli in the vertebrate host.

Santos LF, Rocha FS, Lorenzo MG … +1 more , Guarneri AA

Mem Inst Oswaldo Cruz · 2024 · PMID 39607130 · Full text

BACKGROUND: Trypanosoma rangeli is a haemoflagellate parasite that infects triatomine bugs and mammals in South and Central America. Trypanosoma cruzi, the etiological agent of Chagas disease, has a partially overlapping... BACKGROUND: Trypanosoma rangeli is a haemoflagellate parasite that infects triatomine bugs and mammals in South and Central America. Trypanosoma cruzi, the etiological agent of Chagas disease, has a partially overlapping geographical distribution with T. rangeli, that leads to mixed human infections and cross-reactivity in immunodiagnosis. Although T. rangeli can be detected long after mammal infection, its multiplicative forms have not yet been described. OBJECTIVES: To enhance our understanding of T. rangeli development in mammals, this study assessed various infection parameters in mice over time. METHODS: The parasitaemia, body temperature, and weight of Swiss Webster mice were monitored over 120 days after exposing them to the bites of Rhodnius prolixus nymphs containing metacyclic trypomastigotes in their salivary glands. On day 132 post-infection, spleens and mesenteric lymph nodes were analysed for T. rangeli DNA using polymerase chain reaction (PCR) and quantitative PCR (qPCR). FINDINGS: Parasites were detectable in mice blood since day 2 post-infection, detection peaking on day 5 and becoming undetectable by day 120. PCR and qPCR detected T. rangeli DNA in the spleens and mesenteric lymph nodes of infected mice. Infected mice showed higher body temperatures and a slower weight gain over time compared to controls. MAIN CONCLUSIONS: The study confirmed that T. rangeli establishes a persistent infection in mice, detectable in lymphoid organs long after parasites had disappeared from blood. In addition, infected mice exhibited physiological changes, suggesting potential subclinical effects. These findings highlight the need for further studies on the immune response and potential impacts of T. rangeli infection in mammalian hosts.

Plants of the family Lamiaceae as a source of therapeutic agents against Acanthamoeba infections.

Mrva M, Malíková L, Garajová M

Mem Inst Oswaldo Cruz · 2024 · PMID 39536187 · Full text

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... 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.

Investigating the distribution of a rare Colombo-Venezuelan kissing bug, Rhodnius neivai, Lent, 1953, using geographical information system-based analyses.

Corrêa-do-Nascimento GS, Galvão C, Leite GR

Mem Inst Oswaldo Cruz · 2024 · PMID 39536186 · Full text

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 ecolog... 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.

First comparative genomics analysis of Corynebacterium auriscanis.

Vinhal ALO, de Araújo MRB, Rodrigues EB … +8 more , Castro DLC, Pereira CR, Custódio DAC, Dorneles EMS, Aburjaile FF, Brenig B, Azevedo V, Viana MVC

Mem Inst Oswaldo Cruz · 2024 · PMID 39476150 · Full text

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,... 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.

The Oxente Chagas Bahia Project: evaluating the efficacy of a rapid diagnostic test and treatments for Chagas disease.

Santos FLN, Pavan TBS, Valle CS … +9 more , Sampaio DD, Vasconcelos LCM, Cristóbal MH, Silva ÂAO, Oliveira CM, Souza RS, Casas CNPR, Daher A, Siqueira IC

Mem Inst Oswaldo Cruz · 2024 · PMID 39476029 · Full text

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 morbidit... 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.

Epoxy-a-lapachone in nanosystem: a prototype drug for leishmaniasis assessed in the binomial BALB/c - Leishmania (Leishmania) amazonensis.

Peixoto JF, Gonçalves-Oliveira LF, Dias-Lopes G … +2 more , Souza-Silva F, Alves CR

Mem Inst Oswaldo Cruz · 2024 · PMID 39476028 · Full text

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... 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).

HSV1-induced enhancement of productive HIV-1 replication is associated with interferon pathway downregulation in human macrophages.

Andrade VM, Pereira-Dutra F, Abrantes JL … +2 more , Miranda MD, Souza TML

Mem Inst Oswaldo Cruz · 2024 · PMID 39476027 · Full text

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 disr... 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.

Multiplex PCR assays developed for neglected pathogen detection in undifferentiated acute febrile illness cases in tropical regions.

Carvajal Aristizabal L, Ciuoderis K, Pérez-Restrepo LS … +2 more , Osorio JE, Hernández-Ortiz JP

Mem Inst Oswaldo Cruz · 2024 · PMID 39476026 · Full text

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... 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.

Detached epithelial cell plugs from the upper respiratory tract favour distal lung injury in Golden Syrian hamsters (Mesocricetus auratus) when experimentally infected with the A.2 Brazilian SARS-CoV-2 strain.

Pelajo-Machado M, da Silva ADS, Rodrigues DDRF … +9 more , Paiva MB, Muller R, da Costa LJ, Manso PPA, Dos Santos JPR, da Silva ESRF, Alves ADR, Oliveira JM, Pinto MA

Mem Inst Oswaldo Cruz · 2024 · PMID 39442103 · Full text

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 coro... 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.

First concrete documentation for presence of Aedes (Stegomyia) albopictus in Bolivia: dispelling previous anecdotes.

Lardeux F, Boussès P, Tejerina-Lardeux R … +3 more , Berger A, Barnabé C, Garcia L

Mem Inst Oswaldo Cruz · 2024 · PMID 39417476 · Full text

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. ME... 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.

Rapid on-site detection of echinococcosis and schistosomiasis based on RPA.

Tian L, Shi Y, Yang Y … +1 more , Wang Y

Mem Inst Oswaldo Cruz · 2024 · PMID 39417429 · Full text

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 authori... 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.

Characterization of larval habitats of Anopheles (Nyssorhynchus) darlingi and associated species in malaria areas in western Brazilian Amazon.

Dos Santos F, Xu M, Bravo de Guenni L … +2 more , Lourenço-de-Oliveira R, Rubio-Palis Y

Mem Inst Oswaldo Cruz · 2024 · PMID 39383404 · Full text

BACKGROUND: Anopheles darlingi is the most efficient vector of malaria parasites in the Neotropics. Nevertheless, the specificities of its larval habitats are still poorly known. OBJECTIVES: Characterize permanent larval... BACKGROUND: Anopheles darlingi is the most efficient vector of malaria parasites in the Neotropics. Nevertheless, the specificities of its larval habitats are still poorly known. OBJECTIVES: Characterize permanent larval habitats, and population dynamics of An. darlingi and other potential vectors in relation to climate, physicochemical variables, insect fauna and malaria cases. METHODS: A 14-month longitudinal study was conducted in Porto Velho, Rondônia, western Brazilian Amazon. Monthly, 21 permanent water bodies were sampled. Immature anophelines and associated fauna were collected, physicochemical characteristics, and climate variables were recorded and analyzed. FINDINGS: Five types of habitats were identified: lagoon, stream, stream combined with lagoon, stream combined with dam, and fishpond. A total of 60,927 anophelines were collected. The most abundant species in all habitats were Anopheles braziliensis and An. darlingi. The highest density was found in the lagoon, while streams had the highest species richness. Abundance was higher during the transition period wet-dry season. There was a lag of respectively four and five months between the peak of rainfall and the Madeira River level and the highest abundance of An. darlingi larvae, which were positively correlated with habitats partially shaded, pH close to neutrality, increase dissolved oxygen and sulphates. MAIN CONCLUSIONS: The present study provides data on key factors defining permanent larval habitats for the surveillance of An. darlingi and other potential vectors as well as a log-linear Negative Binomial model based on immature mosquito abundance and climate variables to predict the increase in the number of malaria cases.

Advances in the development of new vaccines for tuberculosis and Brazil's role in the effort forward the end TB strategy.

Junqueira-Kipnis AP, Leite LCC, Croda J … +3 more , Chimara E, Carvalho ACC, Arcêncio RA

Mem Inst Oswaldo Cruz · 2024 · PMID 39383403 · Full text

Tuberculosis (TB) continues to be the world's leading killer of infectious diseases. Despite global efforts to gradually reduce the number of annual deaths and the incidence of this disease, the coronavirus disease 19 (C... Tuberculosis (TB) continues to be the world's leading killer of infectious diseases. Despite global efforts to gradually reduce the number of annual deaths and the incidence of this disease, the coronavirus disease 19 (COVID-19) pandemic caused decreased in TB detection and affected the prompt treatment TB which led to a setback to the 2019 rates. However, the development and testing of new TB vaccines has not stopped and now presents the possibility of implanting in the next five years a new vaccine that is affordable and might be used in the various key vulnerable populations affected by TB. Then, this assay aimed to discuss the main vaccines developed against TB that shortly could be selected and used worldwide, and additionally, evidence the Brazilian potential candidates' vaccines in developing in Brazil that could be considered among those in level advanced to TB end.

Point-of-care testing for COVID-19: a simple two-step molecular diagnostic development and validation during the SARS-CoV-2 pandemic.

Yoshikawa AAG, Cardoso SF, Eslabão LB … +7 more , Pinheiro IC, Valverde P, Caminha G, Romero OB, Medeiros L, Rona LDP, Pitaluga AN

Mem Inst Oswaldo Cruz · 2024 · PMID 39383402 · Full text

BACKGROUND: During the coronavirus disease 19 (COVID-19) pandemic, diagnostic testing of the general population proved challenging due to limitations of the gold-standard diagnostic procedure using reverse transcription... BACKGROUND: During the coronavirus disease 19 (COVID-19) pandemic, diagnostic testing of the general population proved challenging due to limitations of the gold-standard diagnostic procedure using reverse transcription real-time polymerase chain reaction (RT-qPCR) for large-scale testing on the centralised model, especially in low-resource areas. OBJECTIVES: To address this, a point-of-care (PoC) diagnostic protocol for COVID-19 was developed, providing fast, reliable, and affordable testing, particularly for low-mid develop areas. METHODS: The PoC diagnostic process combines a simple paper-based RNA extraction method housed within a 3D-printed plastic device with a colorimetric reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay. Nasopharyngeal/oropharyngeal swabs (NOS) and saliva samples were tested between 2020 and 2021, with the assistance of Santa Catarina's State Health Secretary, Brazil. FINDINGS: The developed diagnostic protocol showed a limit of detection of 9,900 copies and an overall diagnostic specificity of 98% for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from 1,348 clinical analysed samples. The diagnostic sensitivity was 95% for NOS samples, 85% for early morning saliva, and 69% for indiscriminate saliva. MAIN CONCLUSIONS: In conclusion, the developed device successfully extracted SARS-CoV-2 viral RNA from swabs and saliva clinical samples. When combined with colorimetric RT-LAMP, it provides results within 45 min using minimal resources, thus delivering a diagnostic kit protocol that is applicable in large-scale sampling.

Overview of extracellular vesicles in pathogens with special focus on human extracellular protozoan parasites.

Alvarado-Ocampo J, Abrahams-Sandí E, Retana-Moreira L

Mem Inst Oswaldo Cruz · 2024 · PMID 39319874 · Full text

Extracellular vesicles (EVs) are lipid-bilayered membrane-delimited particles secreted by almost any cell type, involved in different functions according to the cell of origin and its state. From these, cell to cell comm... Extracellular vesicles (EVs) are lipid-bilayered membrane-delimited particles secreted by almost any cell type, involved in different functions according to the cell of origin and its state. From these, cell to cell communication, pathogen-host interactions and modulation of the immune response have been widely studied. Moreover, these vesicles could be employed for diagnostic and therapeutic purposes, including infections produced by pathogens of diverse types; regarding parasites, the secretion, characterisation, and roles of EVs have been studied in particular cases. Moreover, the heterogeneity of EVs presents challenges at every stage of studies, which motivates research in this area. In this review, we summarise some aspects related to the secretion and roles of EVs from several groups of pathogens, with special focus on the most recent research regarding EVs secreted by extracellular protozoan parasites.

Description of the new HIV-1 intersubtype B/C circulating recombinant form (CRF146_BC) detected in Brazil.

Oliveira RC, Martin D, de Souza JSM … +4 more , Alcântara LCJ, Guimarães ML, Brites C, Monteiro-Cunha JP

Mem Inst Oswaldo Cruz · 2024 · PMID 39319873 · Full text

BACKGROUND: The human immunodeficiency virus 1 (HIV-1) infections in Brazil are predominantly caused by two subtypes, B and C. OBJECTIVES: Here we present the characterisation of a novel HIV-1 recombinant form, indicatin... BACKGROUND: The human immunodeficiency virus 1 (HIV-1) infections in Brazil are predominantly caused by two subtypes, B and C. OBJECTIVES: Here we present the characterisation of a novel HIV-1 recombinant form, indicating a new Brazilian CRF_BC, named CRF146_BC. METHODS: RDP, JphMM and Simplot recombination tools were used to evaluate the mosaic pattern. FINDINGS: In this work, we identified three HIV-1 nucleotide sequences previously classified as unique recombinant forms (URFs), plus one new partial genome sharing the same BC recombination pattern. The mosaic genome is almost entirely represented by the subtype C sequence, with a small subtype B recombination region in the pol gene, at the Integrase level. The phylogenetic analyses strongly indicate a common origin between the strains, which were isolated in Rio Grande do Sul, Rio de Janeiro and Bahia states. MAIN CONCLUSIONS: Thus, the new HIV-1 CRF146_BC is circulating in three different Brazilian regions: South, Southeast and Northeast.

Climate change-induced degradation of expert range maps drawn for kissing bugs (Hemiptera: Reduviidae) and long-standing current and future sampling gaps across the Americas.

Shirey V, Rabinovich J

Mem Inst Oswaldo Cruz · 2024 · PMID 39319872 · Full text

BACKGROUND: Kissing bugs are the vectors of Trypanosoma cruzi, the etiological agent of Chagas disease (CD). Despite their epidemiological relevance, kissing bug species are under sampled in terms of their diversity and... BACKGROUND: Kissing bugs are the vectors of Trypanosoma cruzi, the etiological agent of Chagas disease (CD). Despite their epidemiological relevance, kissing bug species are under sampled in terms of their diversity and it is unclear what biases exist in available kissing bug data. Under climate change, range maps for kissing bugs may become less accurate as species shift their ranges to track climatic tolerance. OBJECTIVES: Quantify inventory completeness in available kissing bug data. Assess how well range maps are at conveying information about current distributions and potential future distributions subject to shift under climate change. Intersect forecasted changes in kissing bug distributions with contemporary sampling gaps to identify regions for future sampling of the group. Identify whether a phylogenetic signal is present in expert range knowledge as more closely related species may be similarly well or lesser understood. METHODS: We used species distribution models (SDM), specifically constructed from Bayesian additive regression trees, with Bioclim variables, to forecast kissing bug distributions into 2100 and intersect these with current sampling gaps to identify priority regions for sampling. Expert range maps were assessed by the agreement between the expert map and SDM generated occurrence probability. We used classical hypothesis testing methods as well as tests of phylogenetic signal to meet our objectives. FINDINGS: Expert range maps vary in their quality of depicting current kissing bug distributions. Most expert range maps decline in their ability to convey information about kissing bug occurrence over time, especially in under sampled areas. We found limited evidence for a phylogenetic signal in expert range map performance. MAIN CONCLUSIONS: Expert range maps are not a perfect account of species distributions and may degrade in their ability to accurately convey distribution knowledge under future climates. We identify regions where future sampling of kissing bugs will be crucial for completing biodiversity inventories.

HIV-1 controllers exhibit an enhanced antiretroviral innate state characterised by overexpression of p21 and MCPIP1 and silencing of ERVK-6 RNA expression.

de Azevedo SSD, Ribeiro-Alves M, Côrtes FH … +8 more , Delatorre E, Hoagland B, Villela LM, Grinsztejn B, Veloso VG, Morgado MG, Souza TML, Bello G

Mem Inst Oswaldo Cruz · 2024 · PMID 39292108 · Full text

BACKGROUND: Human immunodeficiency virus (HIV)-1 infection can activate the expression of human endogenous retroviruses (HERVs), particularly HERV-K (HML-2). HIV controllers (HICs) are rare people living with HIV (PLWHs)... BACKGROUND: Human immunodeficiency virus (HIV)-1 infection can activate the expression of human endogenous retroviruses (HERVs), particularly HERV-K (HML-2). HIV controllers (HICs) are rare people living with HIV (PLWHs) who naturally control HIV-1 replication and overexpress some cellular restriction factors that negatively regulate the LTR-driven transcription of HIV-1 proviruses. OBJECTIVES: To understand the ability of HICs to control the expression of endogenous retroviruses. METHODS: We measured endogenous retrovirus type K6 (ERVK-6) RNA expression in peripheral blood mononuclear cells (PBMCs) of HICs (n = 23), antiretroviral (ART)-suppressed subjects (n = 8), and HIV-1-negative (NEG) individuals (n = 10) and correlated the transcript expression of ERVK-6 with multiple HIV-1 cellular restriction factors. FINDINGS: Our study revealed that ERVK-6 RNA expression in PBMCs from HICs was significantly downregulated compared with that in both the ART and NEG control groups. Moreover, we detected that ERVK-6 RNA levels in PBMCs across all groups were negatively correlated with the expression levels of p21 and MCPIP1, two cellular restriction factors that limit the activation of macrophages and T cells by downregulating the activity of NF-kB. MAIN CONCLUSIONS: These findings support the hypothesis that HICs activate innate antiviral mechanisms that may simultaneously downregulate the transcription of both exogenous (HIV-1) and endogenous (ERVK-6) retroviruses. Future studies with larger cohorts should be performed to confirm this hypothesis and to explore the role of p21 and MCPIP1 in regulating HERV-K expression in physiological and pathological conditions.
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