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1.
Emerg Microbes Infect ; 13(1): 2362941, 2024 Dec.
Article En | MEDLINE | ID: mdl-38813649

Chikungunya virus (CHIKV) has emerged as a significant public health concern due to its rapid spread and potential for causing debilitating epidemics. In Argentina, the virus has garnered attention since its introduction to the Americas in 2013, due to its growing incidence and impact in neighbouring countries. Here we present a comprehensive analysis of the spatiotemporal dynamics of CHIKV in Argentina, focusing on the evolutionary trajectory of its genetic variants. Through a combination of active surveillance, screening of historical and recent samples, and whole-genome sequencing, we traced the evolutionary history of CHIKV lineages circulating within the country. Our results reveal that two distinct genotypes circulated in Argentina: The Asian lineage during the 2016 epidemic and the ECSA lineage in 2023. This distribution reflects the dominance of particular variants across Latin America. Since 2023, the ECSA lineage has led to a surge in cases throughout the Americas, marking a significant shift. The replacement of lineages in the American region constitutes a major epidemiological event, potentially affecting the dynamics of virus transmission and the clinical outcomes in impacted populations. The spatiotemporal analysis highlights CHIKV's distribution across Argentina and underscores the significant role of human mobility, especially when considering recent epidemics in neighbouring countries such as Paraguay and Uruguay, which have facilitated the spread and introduction of the viral strain into different districts. By integrating epidemiological data with genomic insights, we elucidate the patterns of virus dissemination, highlighting key areas of transmission and potential factors contributing to its spread.


Chikungunya Fever , Chikungunya virus , Evolution, Molecular , Genotype , Phylogeny , Argentina/epidemiology , Chikungunya virus/genetics , Chikungunya virus/classification , Chikungunya virus/isolation & purification , Chikungunya Fever/epidemiology , Chikungunya Fever/virology , Chikungunya Fever/transmission , Humans , Genome, Viral , Latin America/epidemiology , Whole Genome Sequencing , Spatio-Temporal Analysis , Genetic Variation
2.
Emerg Microbes Infect ; 13(1): 2332672, 2024 Dec.
Article En | MEDLINE | ID: mdl-38517841

Uruguay experienced its first Chikungunya virus outbreak in 2023, resulting in a significant burden to its healthcare system. We conducted analysis based on real-time genomic surveillance (30 novel whole genomes) to offer timely insights into recent local transmission dynamics and eco-epidemiological factors behind its emergence and spread in the country.


Chikungunya virus , Chikungunya virus/genetics , Uruguay/epidemiology , Americas/epidemiology , Disease Outbreaks , Genomics
3.
medRxiv ; 2024 Feb 15.
Article En | MEDLINE | ID: mdl-38405721

We employ a multidisciplinary approach, integrating genomics and epidemiology, to uncover recent dengue virus transmission dynamics in the Dominican Republic. Our results highlight a previously unknown north-south transmission pathway within the country, with the co-circulation of multiple virus lineages. Additionally, we examine the historical climate data, revealing long-term trends towards higher theoretical potential for dengue transmission due to rising temperatures. These findings provide information for targeted interventions and resource allocation, informing as well towards preparedness strategies for public health agencies in mitigating climate and geo-related dengue risks.

4.
Nat Commun ; 15(1): 1837, 2024 Feb 28.
Article En | MEDLINE | ID: mdl-38418815

Latin America and Caribbean (LAC) regions were an important epicenter of the COVID-19 pandemic and SARS-CoV-2 evolution. Through the COVID-19 Genomic Surveillance Regional Network (COVIGEN), LAC countries produced an important number of genomic sequencing data that made possible an enhanced SARS-CoV-2 genomic surveillance capacity in the Americas, paving the way for characterization of emerging variants and helping to guide the public health response. In this study we analyzed approximately 300,000 SARS-CoV-2 sequences generated between February 2020 and March 2022 by multiple genomic surveillance efforts in LAC and reconstructed the diffusion patterns of the main variants of concern (VOCs) and of interest (VOIs) possibly originated in the Region. Our phylogenetic analysis revealed that the spread of variants Gamma, Lambda and Mu reflects human mobility patterns due to variations of international air passenger transportation and gradual lifting of social distance measures previously implemented in countries. Our results highlight the potential of genetic data to reconstruct viral spread and unveil preferential routes of viral migrations that are shaped by human mobility patterns.


COVID-19 , SARS-CoV-2 , Humans , SARS-CoV-2/genetics , Latin America/epidemiology , Pandemics , Phylogeny , COVID-19/epidemiology , Caribbean Region/epidemiology
5.
Viruses ; 16(1)2024 01 04.
Article En | MEDLINE | ID: mdl-38257783

In recent months, Paraguay has been grappled with a notable monkeypox outbreak, straining its healthcare infrastructure. The sudden spike in cases underlines the imperative need for a comprehensive understanding of the virus's dynamics, enabling the formulation of robust containment measures. To address this challenge, our team joined forces with the Central Public Health Laboratory of Asunción and the Pan-American Health Organization. Through this collaboration, we employed portable whole-genome sequencing combined with phylodynamic analysis to examine the MPXV strains circulating in Paraguay. Our genomic monitoring approach has produced the first 30 whole-genome sequences from Paraguay, all of which were identified under lineage IIb. Interestingly, our data suggest that the origin of the monkeypox virus in Paraguay at the beginning of 2022 can be traced back to Brazil. This introduction subsequently catalyzed further community spread that was further exacerbated by several independent introduction events as time progressed. These findings not only shed light on the transmission patterns of the virus but also highlight the pivotal role such insights play in sculpting effective response strategies and driving impactful public health measures. Furthermore, our findings strongly advocate intensified surveillance at international borders, ensuring swift detection and proactive countermeasures against potential outbreaks in the future.


Epidemics , Mpox (monkeypox) , Humans , Mpox (monkeypox)/epidemiology , Paraguay/epidemiology , Genomics , Disease Outbreaks
6.
medRxiv ; 2023 Sep 06.
Article En | MEDLINE | ID: mdl-37732223

We report the first whole-genome sequences of Dengue Virus type I genotypes I and V from Uruguay, including the first cases ever reported in the country. Through timely genomic analysis, identification of these genotypes was possible, aiding in timely public health responses and intervention strategies to mitigate the impact of dengue outbreaks.

7.
medRxiv ; 2023 Aug 20.
Article En | MEDLINE | ID: mdl-37646000

Uruguay experienced its first Chikungunya virus outbreak in 2023, resulting in a significant burden to its healthcare system. We conducted analysis based on real-time genomic surveillance (30 novel whole genomes) to offer timely insights into recent local transmission dynamics and eco-epidemiological factors behind its emergence and spread in the country.

8.
Life Sci Alliance ; 6(11)2023 11.
Article En | MEDLINE | ID: mdl-37604582

The Cox6 subunit of Saccharomyces cerevisiae cytochrome oxidase (COX) and the Atp9 subunit of the ATP synthase are encoded in nuclear and mitochondrial DNA, respectively. The two proteins interact to form Atco complexes that serve as the source of Atp9 for ATP synthase assembly. To determine if Atco is also a precursor of COX, we pulse-labeled Cox6 in isolated mitochondria of a cox6 nuclear mutant with COX6 in mitochondrial DNA. Only a small fraction of the newly translated Cox6 was found to be present in Atco, which can explain the low concentration of COX and poor complementation of the cox6 mutation by the allotopic gene. This and other pieces of evidence presented in this study indicate that Atco is an obligatory source of Cox6 for COX biogenesis. Together with our finding that atp9 mutants fail to assemble COX, we propose a regulatory model in which Atco unidirectionally couples the biogenesis of COX to that of the ATP synthase to maintain a proper ratio of these two complexes of oxidative phosphorylation.


Mitochondrial Proton-Translocating ATPases , Saccharomyces cerevisiae Proteins , DNA, Mitochondrial , Electron Transport Complex IV/genetics , Mitochondria , Mutation , Saccharomyces cerevisiae/metabolism , Mitochondrial Proton-Translocating ATPases/metabolism , Saccharomyces cerevisiae Proteins/metabolism
9.
IUBMB Life ; 75(12): 972-982, 2023 Dec.
Article En | MEDLINE | ID: mdl-37470229

The insertion of genes into mitochondria by biolistic transformation is currently only possible in the yeast Saccharomyces cerevisiae and the algae Chlamydomonas reinhardtii. The fact that S. cerevisiae mitochondria can exist with partial (ρ- mutants) or complete deletions (ρ0 mutants) of mitochondrial DNA (mtDNA), without requiring a specific origin of replication, enables the propagation of exogenous sequences. Additionally, mtDNA in this organism undergoes efficient homologous recombination, making it well-suited for genetic manipulation. In this review, we present a summarized historical overview of the development of biolistic transformation and discuss iconic applications of the technique. We also provide a detailed example on how to obtain transformants with recombined foreign DNA in their mitochondrial genome.


DNA, Mitochondrial , Saccharomyces cerevisiae , DNA, Mitochondrial/genetics , Saccharomyces cerevisiae/genetics , Biolistics/methods , Transformation, Genetic , Mitochondria/genetics
11.
Viruses ; 15(6)2023 05 30.
Article En | MEDLINE | ID: mdl-37376575

Dengue virus (DENV) has been a major public health concern in Paraguay, with frequent outbreaks occurring since early 1988. Although control measures have been implemented, dengue remains a significant health threat in the country, and continued efforts are required for prevention and control. In response to that, in collaboration with the Central Public Health Laboratory in Asunción, we conducted a portable whole-genome sequencing and phylodynamic analysis to investigate DENV viral strains circulating in Paraguay over the past epidemics. Our genomic surveillance activities revealed the co-circulation of multiple DENV serotypes: DENV-1 genotype V, the emerging DENV-2 genotype III, BR4-L2 clade, and DENV-4 genotype II. Results additionally highlight the possible role of Brazil as a source for the international dispersion of different viral strains to other countries in the Americas emphasizing the need for increased surveillance across the borders, for the early detection and response to outbreaks. This, in turn, emphasizes the critical role of genomic surveillance in monitoring and understanding arbovirus transmission and persistence locally and over long distances.


Dengue Virus , Dengue , Humans , Dengue Virus/genetics , Dengue/epidemiology , Paraguay/epidemiology , Retrospective Studies , Phylogeny , Serogroup , Genotype
12.
medRxiv ; 2023 Apr 17.
Article En | MEDLINE | ID: mdl-37131602

The spread of vector-borne viruses, such as CHIKV, is a significant public health concern in the Americas, with over 120,000 cases and 51 deaths in 2023, of which 46 occurred in Paraguay. Using a suite of genomic, phylodynamic, and epidemiological techniques, we characterized the ongoing large CHIKV epidemic in Paraguay. Article Summary Line: Genomic and epidemiological characterization of the ongoing Chikungunya virus epidemic in Paraguay.

13.
Environ Microbiol Rep ; 15(2): 119-128, 2023 04.
Article En | MEDLINE | ID: mdl-36629129

Salmonella serovars Heidelberg and Minnesota encoding antimicrobial resistance to third-generation cephalosporins and fluoroquinolones are often detected in poultry/poultry meat. We analysed the genomes of 10 Salmonella Heidelberg (SH) and 4 Salmonella Minnesota (SM) from faecal isolates of Brazilian poultry. These featured virulent and multidrug-resistant characteristics, with AmpC beta-lactamase (blaCMY-2 ) predominance (9/14), for all SM (4/4) and some SH (3/10) located on IncC plasmid replicons. IncC carrying blaCTX-M-2 was only detected among SH (3/10). Mutation in the gyrA/parC genes was present in all SH, whereas SM harboured parC mutation plus qnrB19 on ColRNAI plasmids (3/4). In silico resistance overall corroborated with phenotypic results. Core genome phylogenies showed close clustering and high similarities between the Brazilian and poultry meat/food isolates from Europe, and to human isolates from European countries with documented import of Brazilian poultry meat. Conjugation assays with SM successfully transferred blaCMY-2 , and qnrB19 to an Escherichia coli recipient. The findings reinforce the ongoing antimicrobial resistance acquisition of SH and Minnesota and the risks for disseminating resistant strains and/or mobile elements which may increasingly affect importing countries and the need for controlling AMR in major poultry-exporting countries like Brazil.


Anti-Bacterial Agents , Fluoroquinolones , Animals , Humans , Fluoroquinolones/pharmacology , Anti-Bacterial Agents/pharmacology , Chickens/genetics , Brazil , Drug Resistance, Multiple, Bacterial/genetics , beta-Lactamases/genetics , Poultry/genetics , Salmonella/genetics , Escherichia coli/genetics , Plasmids/genetics , Cephalosporins/pharmacology , Genomics
14.
Article En | LILACS, CONASS, ColecionaSUS, SES-SP, SESSP-IALPROD, SES-SP | ID: biblio-1417271

Salmonella serovars Heidelberg and Minnesota encoding antimicrobial resistance to third-generation cephalosporins and fluoroquinolones are often detected in poultry/poultry meat. We analysed the genomes of 10 Salmonella Heidelberg (SH) and 4 Salmonella Minnesota (SM) from faecal isolates of Brazilian poultry. These featured virulent and multidrug-resistant characteristics, with AmpC beta-lactamase (blaCMY-2 ) predominance (9/14), for all SM (4/4) and some SH (3/10) located on IncC plasmid replicons. IncC carrying blaCTX-M-2 was only detected among SH (3/10). Mutation in the gyrA/parC genes was present in all SH, whereas SM harboured parC mutation plus qnrB19 on ColRNAI plasmids (3/4). In silico resistance overall corroborated with phenotypic results. Core genome phylogenies showed close clustering and high similarities between the Brazilian and poultry meat/food isolates from Europe, and to human isolates from European countries with documented import of Brazilian poultry meat. Conjugation assays with SM successfully transferred blaCMY-2 , and qnrB19 to an Escherichia coli recipient. The findings reinforce the ongoing antimicrobial resistance acquisition of SH and Minnesota and the risks for disseminating resistant strains and/or mobile elements which may increasingly affect importing countries and the need for controlling AMR in major poultry-exporting countries like Brazil.


Salmonella , Sprains and Strains , Cephalosporins
15.
Viruses ; 16(1)2023 12 22.
Article En | MEDLINE | ID: mdl-38257724

The emergence and continued geographic expansion of arboviruses and the growing number of infected people have highlighted the need to develop and improve multiplex methods for rapid and specific detection of pathogens. Sequencing technologies are promising tools that can help in the laboratory diagnosis of conditions that share common symptoms, such as pathologies caused by emerging arboviruses. In this study, we integrated nanopore sequencing and the advantages of reverse transcription polymerase chain reaction (RT-PCR) to develop a multiplex RT-PCR protocol for the detection of Chikungunya virus (CHIKV) and several orthoflaviviruses (such as dengue (Orthoflavivirus dengue), Zika (Orthoflavivirus zikaense), yellow fever (Orthoflavivirus flavi), and West Nile (Orthoflavivirus nilense) viruses) in a single reaction, which provides data for sequence-based differentiation of arbovirus lineages.


Arboviruses , Chikungunya virus , Dengue , Nanopore Sequencing , Zika Virus Infection , Zika Virus , Humans , Arboviruses/genetics , Chikungunya virus/genetics , Multiplex Polymerase Chain Reaction , Zika Virus/genetics
16.
Dialogues Health ; 2: 100117, 2023 Dec.
Article En | MEDLINE | ID: mdl-38515494

Background: This work aims to analyze the landscape of scientific publications on subjects related to One Health and infectious diseases in Panama. The research questions are: How does the One Health research landscape look like in Panama? Are historical research efforts aligned with the One Health concept? What infectious diseases have received more attention from the local scientific community since 1990? Methods: Boolean searches on the Web of Science, SCOPUS and PubMed were undertaken to evaluate the main trends of publications related to One Health and infectious disease research in the country of Panama, between 1990 and 2019. Results: 4546 publications were identified since 1990, including 3564 peer-reviewed articles interconnected with One Health related descriptors, and 211 articles focused particularly on infectious diseases. A pattern of exponential growth in the number of publications with various contributions from Panamanian institutions was observed. The rate of multidisciplinary research was moderate, whereas those of interinstitutional and intersectoral research ranged from low to very low. Research efforts have centered largely on protozoan, neglected and arthropod-borne diseases with a strong emphasis on malaria, Chagas and leishmaniasis. Conclusion: Panama has scientific capabilities on One Health to tackle future infectious disease threats, but the official collaboration schemes and strategic investment to develop further competencies need to be conciliated with modern times, aka the pandemics era. The main proposition here, addressed to the government of Panama, is to launch a One Health regional center to promote multidisciplinary, interinstitutional and intersectoral research activities in Panama and beyond.

17.
Prog Orthod ; 23(1): 29, 2022 Aug 08.
Article En | MEDLINE | ID: mdl-35934732

OBJECTIVE: To perform a case series analysis of the changes in the pulmonary artery systolic pressure (PASP), nasal inspiratory flow (NIF), upper airway volume, obstructive apnea/hypopnea index (OAHI), and the maxillomandibular three-dimensional (3D) morphology after adenotonsillectomy (T&A) of obstructive sleep apnea children (OSA). MATERIALS AND METHODS: Retrospective assessment of files from 1002 children screened between 2012 and 2020 in a hospital-based mouth-breather referral center. From this universe, 15 obstructive sleep apnea children (7 females; 8 males), ages 4.1 to 8.9 years old (mean age of 5.4 years ± 1.3), who presented indications of tonsillectomy and/or adenoidectomy were selected. The complete baseline examination (T0) was carried out before T&A and a second complete examination (T1) was made 18.7-month follow-up after T&A (ranging from 12 to 30 months). Eleven patients were submitted to T&A, and four patients had indications but did not receive authorization for surgery from the public health system. According to the protocol of the outpatient clinic for OSA patients, Doppler echocardiography, polysomnography, rhinomanometry, and computed tomography imaging was performed at (T0) and (T1). RESULTS: PASP decreased 16.6% after T&A. NIF increased more in T&A children (40.3%) than in non-T&A children (16.8%). The upper airway volume increased in T&A and non-T&A children, but greater volumetric gain (45.6%) was found in the nasopharynx of T&A patients. OAHI did not change in six T&A children (55%) and three non-T&A children (75%). The maxilla displaced downward and backward relative to the cranial base in six T&A children (55%) and two untreated children (50%). Nine of the T&A children (85%) and three untreated children (75%) presented extensive condylar growth and increased mandibular length. The qualitative 3D assessment showed similar morphological 3D changes in T&A and non-T&A patients. CONCLUSION: Pulmonary artery systolic pressure decreased, nasal inspiratory flow increased, and nasopharynx volume increased following adenotonsillectomy, but obstructive apnea/hypopnea index and maxillomandibular morphology were similar in surgical and non-surgical patients.


Sleep Apnea, Obstructive , Tonsillectomy , Adenoidectomy/methods , Child , Child, Preschool , Female , Humans , Male , Polysomnography , Retrospective Studies , Sleep Apnea, Obstructive/surgery , Tonsillectomy/methods
19.
J Biol Chem ; 298(8): 102214, 2022 08.
Article En | MEDLINE | ID: mdl-35779633

Mitochondrial translation is a highly regulated process, and newly synthesized mitochondrial products must first associate with several nuclear-encoded auxiliary factors to form oxidative phosphorylation complexes. The output of mitochondrial products should therefore be in stoichiometric equilibrium with the nuclear-encoded products to prevent unnecessary energy expense or the accumulation of pro-oxidant assembly modules. In the mitochondrial DNA of Saccharomyces cerevisiae, COX1 encodes subunit 1 of the cytochrome c oxidase and COB the central core of the cytochrome bc1 electron transfer complex; however, factors regulating the expression of these mitochondrial products are not completely described. Here, we identified Mrx9p as a new factor that controls COX1 and COB expression. We isolated MRX9 in a screen for mitochondrial factors that cause poor accumulation of newly synthesized Cox1p and compromised transition to the respiratory metabolism. Northern analyses indicated lower levels of COX1 and COB mature mRNAs accompanied by an accumulation of unprocessed transcripts in the presence of excess Mrx9p. In a strain devoid of mitochondrial introns, MRX9 overexpression did not affect COX1 and COB translation or respiratory adaptation, implying Mrx9p regulates processing of COX1 and COB RNAs. In addition, we found Mrx9p was localized in the mitochondrial inner membrane, facing the matrix, as a portion of it cosedimented with mitoribosome subunits and its removal or overexpression altered Mss51p sedimentation. Finally, we showed accumulation of newly synthesized Cox1p in the absence of Mrx9p was diminished in cox14 null mutants. Taken together, these data indicate a regulatory role of Mrx9p in COX1 RNA processing.


Electron Transport Complex III/genetics , Electron Transport Complex IV/genetics , Saccharomyces cerevisiae Proteins/genetics , Saccharomyces cerevisiae , DNA, Mitochondrial/genetics , DNA, Mitochondrial/metabolism , Electron Transport Complex III/metabolism , Electron Transport Complex IV/metabolism , Mitochondrial Proteins/genetics , Mitochondrial Proteins/metabolism , Oxidative Phosphorylation , RNA/metabolism , Saccharomyces cerevisiae/genetics , Saccharomyces cerevisiae/metabolism , Saccharomyces cerevisiae Proteins/metabolism
20.
PLoS One ; 17(3): e0252526, 2022.
Article En | MEDLINE | ID: mdl-35239677

The timely release of SARS-CoV-2 first genomic sequences allowed the identification of the etiologic agent and development of diagnostic protocols. Genomic sequencing was a crucial step in generating data for driving laboratory response and detections of SARS-CoV-2 since the start of the COVID-19 pandemic. Because of all the progression and achievements that timely release of genetic sequence data represents in the public health response, the Pan American Health Organization (PAHO) in collaboration with countries' public health laboratories, started implementation of a network for strengthening the Latin America and Caribbean (LAC) region on timely generation of SARS-CoV-2 genomic data. Here we describe the implementation of the COVID-19 Genomic Surveillance Regional Network in the Americas region during the beginning of the pandemic. The establishment of this network has strengthened laboratory response capacity at the country level, as well as facilitated timely release of SARS-CoV-2 genomic information to be used to complement the multiple response strategies for COVID-19 pandemic mitigation. As genomic epidemiology is useful for guiding public health decisions on outbreak and response, we also analysed the first SARS-CoV-2 genomic sequence data from countries of the Latin America and Caribbean Region.


Pandemics
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