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1.
Eur J Med Chem ; 278: 116808, 2024 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-39236495

RESUMEN

Chikungunya virus (CHIKV) is responsible for the most endemic alphavirus infections called Chikungunya. The endemicity of Chikungunya has increased over the past two decades, and it is a pathogen with pandemic potential. There is currently no approved direct-acting antiviral to treat the disease. As part of our antiviral drug discovery program focused on alphaviruses and the non-structural protein 2 protease, we discovered that J12 and J13 can inhibit CHIKV nsP2 protease and block the replication of CHIKV in cell cultures. Both compounds are metabolically stable to human liver microsomal and S9 enzymes. J13 has excellent oral bioavailability in pharmacokinetics studies in mice and ameliorated Chikungunya symptoms in preliminary efficacy studies in mice. J13 exhibited an excellent safety profile in in vitro safety pharmacology and off-target screening assays, making J13 and its analogs good candidates for drug development against Chikungunya.


Asunto(s)
Antivirales , Fiebre Chikungunya , Virus Chikungunya , Modelos Animales de Enfermedad , Animales , Virus Chikungunya/efectos de los fármacos , Ratones , Fiebre Chikungunya/tratamiento farmacológico , Antivirales/farmacología , Antivirales/química , Antivirales/síntesis química , Humanos , Inhibidores de Proteasas/farmacología , Inhibidores de Proteasas/química , Inhibidores de Proteasas/síntesis química , Relación Estructura-Actividad , Relación Dosis-Respuesta a Droga , Estructura Molecular , Cisteína Endopeptidasas/metabolismo , Microsomas Hepáticos/metabolismo , Replicación Viral/efectos de los fármacos
2.
Curr Pharm Des ; 2024 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-39225215

RESUMEN

The 21st century has shown us how rapidly the pandemic can evolve and devastate the life of human beings without differentiating between the continents. Even after the global investment of billions of dollars into the healthcare sector, we are still lacking multiple therapeutics against emerging viruses. World Health Organization (WHO) has listed a number of viruses that could take the form of pandemics at anytime, depending upon their mutations. Among those listed, the SARS-CoV, Ebola, Zika, Nipah, and Chikungunya (CHIKV) are the most known viruses in terms of their number of outbreaks. The common feature among these viruses is their RNA-based genome. Developing a new therapeutic candidate for these RNA viruses in a short period of time is challenging. In-silico drug designing techniques offer a simple solution to these problems by implementing supercomputers and complicated algorithms that can evaluate the inhibition activity of proposed synthetic compounds without actually doing the bioassays. A vast collection of protein crystal structures and the data on binding affinity are useful tools in this process. Taking this into account, we have summarized the in-silico based therapeutic advances against SARS-CoV, Ebola, Zika, Nipah, and CHIKV viruses by encapsulating state-of-art research articles into different sections. Specifically, we have shown that computer- aided drug design (CADD) derived synthetic molecules are the pillars of upcoming therapeutic strategies against emerging and neglected viruses.

3.
Microbiome ; 12(1): 161, 2024 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-39223641

RESUMEN

BACKGROUND: Many studies have demonstrated the association between intestinal microbiota and joint diseases. The "gut-joint axis" also has potential roles in chikungunya virus (CHIKV) infection. Pro-inflammatory arthritis after CHIKV infection might disrupt host homeostasis and lead to dysbacteriosis. This study investigated the characteristics of fecal and gut microbiota, intestinal metabolites, and the changes in gene regulation of intestinal tissues after CHIKV infection using multi-omics analysis to explore the involvement of gut microbiota in the pathogenesis of CHIKV infection. RESULTS: CHIKV infection increases the systemic burden of inflammation in the GI system of infected animals. Moreover, infection-induced alterations in GI microbiota and metabolites may be indirectly involved in the modulation of GI and bone inflammation after CHIKV infection, including the modulation of inflammasomes and interleukin-17 inflammatory cytokine levels. CONCLUSION: Our results suggest that the GI tract and its microbes are involved in the modulation of CHIKV infection, which could serve as an indicator for the adjuvant treatment of CHIKV infection. Video Abstract.


Asunto(s)
Fiebre Chikungunya , Virus Chikungunya , Heces , Microbioma Gastrointestinal , Macaca mulatta , Animales , Heces/microbiología , Fiebre Chikungunya/virología , Bacterias/clasificación , Bacterias/metabolismo , Bacterias/aislamiento & purificación , Bacterias/genética , Disbiosis/microbiología , Inflamación , Inflamasomas/metabolismo , Modelos Animales de Enfermedad , Interleucina-17/metabolismo , Tracto Gastrointestinal/microbiología , Citocinas/metabolismo
4.
Chem Biodivers ; : e202401241, 2024 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-39137144

RESUMEN

The non-structural protein (nsP2 & nsP3) of the CHIKV is responsible for the transmission of viral infection. The main role of nsp is involved in the transcription process at an early stage of the infection. In this work, authors have studied the impact of nsP2 and nsP3 of CHIKV on hormones present in the human body using a computational approach. The ten hormones of chemical properties such as 4-Androsterone-2,17-dione, aldosterone, androsterone, corticosterone, cortisol, cortisone, estradiol, estrone, progesterone and testosterone were taken as a potency. From the molecular docking, the binding energy of the complexes is estimated, and cortisone was found to be the highest negative binding energy (-6.57 kcal/mol) with the nsP2 protease and corticosterone with the nsP3 protease (-6.47 kcal/mol). This is based on the interactions between hormones and NsP2/NsP3, which are types of noncovalent intermolecular interactions categorized into three types: electrostatic interactions, van der Waals interactions, and hydrogen-bonding. To validate the docking results, molecular dynamics simulations and MM-GBSA methods were performed. The change in enthalpy, entropy, and free energy were calculated using MM-GBSA methods. The nsP2 and nsP3 protease of CHIKV interact strongly with the cortisone and corticosterone with free energy changes of -20.55 & -36.08 kcal/mol, respectively.

5.
Sci Rep ; 14(1): 18614, 2024 08 10.
Artículo en Inglés | MEDLINE | ID: mdl-39127786

RESUMEN

Chikungunya virus (CHIKV) is a single-stranded RNA virus belonging to the genus Alphavirus and is responsible for causing Chikungunya fever, a type of arboviral fever. Despite extensive research, the pathogenic mechanism of CHIKV within host cells remains unclear. In this study, an in-silico approach was used to predict that CHIKV produces micro-RNAs that target host-specific genes associated with host cellular regulatory pathways. Putative micro-RNAs of CHIKV were predicted using the miRNAFold and Vmir RNA structure web servers, and secondary structure prediction was performed using RNAfold. Host-specific target genes were then predicted, and hub genes were identified using CytoHubba and module selection through MCODE. Functional annotations of hub genes revealed their association with various pathways, including osteoclast differentiation, neuroactive ligand-receptor interaction, and mRNA surveillance. We used the freely available dataset GSE49985 to determine the level of expression of host-specific target genes and found that two genes, F-box and leucine-rich repeat protein 16 (FBXL16) and retinoic acid receptor alpha (RARA), were down-regulated, while four genes, RNA binding protein with serine-rich domain 1 (RNPS1), RNA helicase and ATPase (UPF1), neuropeptide S receptor 1 (NPSR1), and vasoactive intestinal peptide receptor 1 (VIPR1), were up-regulated. These findings provide insight into novel miRNAs and hub genes associated with CHIKV infection and suggest potential targets for therapeutic intervention. Further experimental validation of these targets could lead to the development of effective treatments for CHIKV-mediated diseases.


Asunto(s)
Virus Chikungunya , Biología Computacional , MicroARNs , Virus Chikungunya/genética , Virus Chikungunya/inmunología , MicroARNs/genética , Biología Computacional/métodos , Humanos , Interacciones Huésped-Patógeno/genética , Interacciones Huésped-Patógeno/inmunología , Fiebre Chikungunya/virología , Fiebre Chikungunya/inmunología , Fiebre Chikungunya/genética , ARN Viral/genética , Redes Reguladoras de Genes
6.
Pharmaceutics ; 16(8)2024 Jul 26.
Artículo en Inglés | MEDLINE | ID: mdl-39204339

RESUMEN

Given the increasing aging population and the rising prevalence of musculoskeletal diseases due to obesity and injury, urgent research is needed to formulate new treatment alternatives, as current options remain inadequate. Viruses can exacerbate arthritis and worsen symptoms in patients with pre-existing osteoarthritis. Over the past decade, the chikungunya virus (CHIKV) has emerged as a significant public health concern, especially in Asia and South America. Exploring natural products, such as berberine, has shown promise due to its anticatabolic, antioxidative, and anti-inflammatory effects. However, berberine's low stability and bioavailability limit its efficacy. We hypothesized that encapsulating berberine into a proniosome gel, known for its ease of preparation and stability, could enhance its bioavailability and efficacy when applied topically, potentially treating CHIKV infection. Our investigation focused on how varying berberine loads and selected excipients in the proniosome gel influenced its physical properties, stability, and skin permeability. We also examined the biological half-life of berberine in plasma upon topical administration in mice to assess the potential for controlled and sustained drug release. Additionally, we analyzed the antioxidant stress activity and cell viability of HaCaT keratinocytes and developed a lipopolysaccharide-stimulated cell culture model to evaluate anti-inflammatory effects using pro-inflammatory cytokines. Overall, the research aims to transform the treatment landscape for arthritis by leveraging berberine's therapeutic potential.

7.
Vaccines (Basel) ; 12(8)2024 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-39204019

RESUMEN

The first vaccine against chikungunya virus (CHIKV) was recently licensed in the U.S., Europe, and Canada (brand IXCHIQ®, referred to as VLA1553). Other pathogenic alphaviruses co-circulate with CHIKV and major questions remain regarding the potential of IXCHIQ to confer cross-protection for populations that are exposed to them. Here, we characterized the cross-neutralizing antibody (nAb) responses against heterotypic CHIKV and additional arthritogenic alphaviruses in individuals at one month, six months, and one year post-IXCHIQ vaccination. We characterized nAbs against CHIKV strains LR2006, 181/25, and a 2021 isolate from Tocantins, Brazil, as well as O'nyong-nyong virus (ONNV), Mayaro virus (MAYV), and Ross River virus (RRV). IXCHIQ elicited 100% seroconversion to each virus, with the exception of RRV at 83.3% seroconversion of vaccinees, and cross-neutralizing antibody potency decreased with increasing genetic distance from CHIKV. We compared vaccinee responses to cross-nAbs elicited by natural CHIKV infection in individuals living in the endemic setting of Puerto Rico at 8-9 years post-infection. These data suggest that IXCHIQ efficiently and potently elicits cross-nAb breadth that extends to related alphaviruses in a manner similar to natural CHIKV infection, which may have important implications for individuals that are susceptible to alphavirus co-circulation in regions of potential vaccine rollout.

8.
J Travel Med ; 2024 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-38959854

RESUMEN

BACKGROUND: Chikungunya is a serious and debilitating viral infection with a significant disease burden. VLA1553 (IXCHIQ®) is a live-attenuated vaccine licensed for active immunization for prevention of disease caused by chikungunya virus (CHIKV). METHODS: Immunogenicity following a single dose of VLA1553 was evaluated in healthy adults aged ≥18 years in two Phase 3 trials (N = 656 participants [per protocol analysis set]). Immunogenicity data to 180 days post-vaccination (geometric mean titers [GMTs], seroresponse rate, seroconversion rate) were pooled for the two trials. A comparison of subgroups based on age, sex, body mass index (BMI), race, and baseline seropositivity was included. All analyses were descriptive. RESULTS: Most participants were aged 18-64 years (N = 569/656 [86.7%]), there were slightly more females (N = 372/656 [56.7%]), most were not Hispanic/Latino (N = 579/656 [88.3%]), and most were White (N = 517/656 [78.8%]). In baseline seronegative participants, GMT peaked at Day 29 post-vaccination, and subsequently declined slightly but remained elevated until Day 180. At Days 29, 85, and 180, seroresponse rate was 98.3%, 97.7%, and 96.4% and seroconversion rate was 98.5%, 98.4%, and 98.2%. There were no differences in seroresponse rate in participants aged 18-64 years or ≥ 65 years at Day 29 (98.1% versus 100%), Day 85 (97.4% versus 100%), and Day 180 (96.3% versus 96.5%) nor based on sex, BMI, ethnicity, or race. An immune response was shown in a small heterogenous population of baseline seropositive participants, with GMTs showing the same trend as baseline seronegative participants. CONCLUSIONS: A single dose of VLA1553 elicited a very strong immune response by Day 29 that remained elevated at Day 180 in both baseline seronegative and seropositive participants in a combined evaluation of two Phase 3 trials. The vaccine was similarly immunogenic in participants aged ≥65 years and 18-64 years, and there were no differences based on subgroup analyses for sex, BMI, ethnicity, or race.

9.
Microbiol Resour Announc ; 13(9): e0032624, 2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-39083697

RESUMEN

Here, we report the complete genome sequence of an Indian strain of chikungunya virus isolated from an infected patient from Hyderabad, Andhra Pradesh, India, during a massive outbreak in 2005-2006. The genome length spans 11,811 nucleotides and has a poly(A) tail of 29 residues at the 3' end.

10.
Travel Med Infect Dis ; 60: 102737, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38996856

RESUMEN

BACKGROUND: The spread of vector-borne infectious diseases is determined, among other things, by temperature. Thus, climate change will have an influence on their global distribution. In the future, Europe will approach the temperature optimum for the transmission of ZIKV and CHIKV. Climate scenarios and climate models can be used to depict future climatic changes and to draw conclusions about future risk areas for vector-borne infectious diseases. METHODS: Based on the RCP 4.5 and RCP 8.5 climate scenarios, a geospatial analysis was carried out for the future temperature suitability of ZIKV and CHIKV in Europe. The results were presented in maps and the percentage of the affected areas calculated. RESULTS: Due to rising temperatures, the risk areas for transmission of ZIKV and CHIKV spread in both RCP scenarios. For CHIKV transmission, Spain, Portugal, the Mediterranean coast and areas near the Black Sea are mainly affected. Due to high temperatures, large areas throughout Europe are at risk for ZIKV and CHIKV transmission. CONCLUSION: Temperature is only one of many factors influencing the spread of vector-borne infectious diseases. Nevertheless, the representation of risk areas on the basis of climate scenarios allows an assessment of future risk development. Monitoring and adaptation strategies are indispensable for coping with and containing possible future autochthonous transmissions and epidemics in Europe.


Asunto(s)
Fiebre Chikungunya , Cambio Climático , Sistemas de Información Geográfica , Infección por el Virus Zika , Infección por el Virus Zika/epidemiología , Infección por el Virus Zika/transmisión , Humanos , Fiebre Chikungunya/epidemiología , Fiebre Chikungunya/transmisión , Europa (Continente)/epidemiología , Virus Zika , Animales , Medición de Riesgo , Virus Chikungunya , Temperatura
11.
Viruses ; 16(6)2024 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-38932154

RESUMEN

We previously reported that deletion of a 44-nucleotide element in the 3' untranslated region (UTR) of the Chikungunya virus (CHIKV) genome enhances the virulence of CHIKV infection in mice. Here, we find that while this 44-nucleotide deletion enhances CHIKV fitness in murine embryonic fibroblasts in a manner independent of the type I interferon response, the same mutation decreases viral fitness in C6/36 mosquito cells. Further, the fitness advantage conferred by the UTR deletion in mammalian cells is maintained in vivo in a mouse model of CHIKV dissemination. Finally, SHAPE-MaP analysis of the CHIKV 3' UTR revealed this 44-nucleotide element forms a distinctive two-stem-loop structure that is ablated in the mutant 3' UTR without altering additional 3' UTR RNA secondary structures.


Asunto(s)
Regiones no Traducidas 3' , Fiebre Chikungunya , Virus Chikungunya , Replicación Viral , Virus Chikungunya/genética , Virus Chikungunya/fisiología , Animales , Ratones , Fiebre Chikungunya/virología , ARN Viral/genética , Virulencia , Línea Celular , Fibroblastos/virología , Aptitud Genética , Humanos , Eliminación de Secuencia , Conformación de Ácido Nucleico , Modelos Animales de Enfermedad
12.
Cureus ; 16(4): e58188, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38741833

RESUMEN

Background Chikungunya is a mosquito-borne re-emerging disease that has caused a significant number of outbreaks recently in diverse geographic settings across the globe. It leads to severe debilitating illness in a significant proportion of persons who are infected. Measures to limit the impact produced by recurrent outbreaks of the disease are limited and there is an urgent clinical need for early identification of those predisposed to develop severe disease. A comprehensive understanding regarding the proportion of individuals predisposed to developing severe disease is lacking as its correlation with detectable viremia is hinted at by some studies. In this context, we hypothesized that detectable viremia reflected in the diagnostic RT-PCR assay could be significantly associated with the development of severe disease in Chikungunya among those diagnosed on the basis of seroconversion. Our study aims to confirm the same in relation to disease severity among the suspected patients of Chikungunya in the setting of a tertiary care center. Methods In a prospective observational study at a tertiary care center, a total number of 1021 Chikungunya suspects presenting within seven days of illness were screened with Chikungunya Virus IgM ELISA from 2021 to 2023. Those having positive IgM results were further tested with RT-PCR in a blinded manner. According to the information entered into the predesigned form and the hospital follow-up/discharge data, the cases where symptoms like fever and joint pain persisted beyond two weeks were classified as severe versus those resolving within two weeks as mild. The patients in each group were compared for their clinical symptoms and association with the disease severity with detectable viremia (RT-PCR positivity). Results We identified a total of 178 (17.4%) lab-confirmed Chikungunya IgM-positive cases amongst the recruited patients. Here a total of 31 (18.9%) cases could be classified as severe and 133 (74.7%) as mild illness, the remaining 14 patients were excluded from analysis due to insufficient clinical data. Severe illness was significantly higher in elderly individuals belonging to more than 60 years (p = 0.01). Viremia was detected in 16 (9%), those with detectable viremia had higher odds (OR = 4.1) of manifesting as severe disease. Among the severe cases, the proportion of cases with RT-PCR positivity (8, 25.8%) at presentation was significantly higher (P = 0.01) versus those who presented with mild disease (7, 5.5%). Conclusion Our study reveals a correlation between detectable viremia in Chikungunya virus (CHIKV) patients and an increased risk of manifesting into a severe disease, where severe cases exhibited a significantly higher proportion of viremia, indicated by RT-PCR positivity. This study hints at the presence of viremia, joint symptoms, and elderly age as potentially useful clinical predictors of disease outcomes, these may serve as indicators for closer monitoring among individuals seeking medical attention due to Chikungunya infection. However, we need to validate these findings in future longitudinal studies incorporating multiple, time-bound follow-up data on clinical outcomes, viral titers, and its long-term complications.

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

RESUMEN

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.


Asunto(s)
Fiebre Chikungunya , Virus Chikungunya , Evolución Molecular , Genotipo , Filogenia , Argentina/epidemiología , Virus Chikungunya/genética , Virus Chikungunya/clasificación , Virus Chikungunya/aislamiento & purificación , Fiebre Chikungunya/epidemiología , Fiebre Chikungunya/virología , Fiebre Chikungunya/transmisión , Humanos , Genoma Viral , América Latina/epidemiología , Secuenciación Completa del Genoma , Análisis Espacio-Temporal , Variación Genética
14.
J Immunoassay Immunochem ; 45(4): 307-324, 2024 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-38776466

RESUMEN

Single Chain Variable Fragment (scFv), a small fragment of antibody can be used to substitute the monoclonal antibody for diagnostic purposes. Production of scFv in Escherichia coli host has been a challenge due to the potential miss-folding and formation of inclusion bodies. This study aimed to express anti-CHIKV E2 scFv which previously designed specifically for Asian strains by co-expression of three chaperones that play a role in increasing protein solubility; GroEL, GroES, and Trigger Factor. The scFv and chaperones were expressed in Origami B E. coli host under the control of the T7 promoter, and purified using a Ni-NTA column. Functional assay of anti-CHIKV-E2 scFv was examined by electrochemical immunosensor using gold modified Screen Printed Carbon Electrode (SPCE), and characterized by differential pulses voltammetry (DPV) using K3[Fe(CN)6] redox system and scanning microscope electron (SEM). The experimental condition was optimized using the Box-Behnken design. The results showed that co-expression of chaperone increased the soluble scFv yield from 54.405 µg/mL to 220.097 µg/mL (~5×). Furthermore, scFv can be used to detect CHIKV-E2 in immunosensor electrochemistry with a detection limit of 0.74048 ng/mL and a quantification limit of 2,24388 ng/mL. Thus, the scFv-anti-CHIKV-E2 can be applied as a bioreceptor in another immunoassay method.


Asunto(s)
Técnicas Biosensibles , Técnicas Electroquímicas , Escherichia coli , Chaperonas Moleculares , Anticuerpos de Cadena Única , Anticuerpos de Cadena Única/inmunología , Anticuerpos de Cadena Única/química , Anticuerpos de Cadena Única/genética , Escherichia coli/metabolismo , Escherichia coli/genética , Chaperonas Moleculares/inmunología , Inmunoensayo/métodos
15.
Genome Biol Evol ; 16(5)2024 05 02.
Artículo en Inglés | MEDLINE | ID: mdl-38695057

RESUMEN

Transposable elements are mobile repeated sequences found in all genomes. Transposable elements are controlled by RNA interference pathways in most organisms, and this control involves the PIWI-interacting RNA pathway and the small interfering RNA pathway, which is also known to be the first line of antiviral defense in invertebrates. Using Drosophila, we recently showed that viral infections result in the modulation of transposable element transcript levels through modulation of the small RNA repertoire. The Aedes aegypti mosquito is of particular interest because almost half of its genome is made of transposable elements, and it is described as a major vector of viruses (such as the dengue [DENV], Zika [ZIKV], and chikungunya [CHIKV] arboviruses). Moreover, Aedes mosquitoes are unique among insects in that the PIWI-interacting RNA pathway is also involved in the somatic antiviral response, in addition to the transposable element control and PIWI-interacting RNA pathway genes expanded in the mosquito genome. For these reasons, we studied the impacts of viral infections on transposable element transcript levels in A. aegypti samples. We retrieved public datasets corresponding to RNA-seq data obtained from viral infections by DENV, ZIKV, and CHIKV in various tissues. We found that transposable element transcripts are moderately modulated following viral infection and that the direction of the modulation varies greatly across tissues and viruses. These results highlight the need for an in-depth investigation of the tightly intertwined interactions between transposable elements and viruses.


Asunto(s)
Aedes , Elementos Transponibles de ADN , Animales , Aedes/genética , Aedes/virología , Infecciones por Arbovirus , Mosquitos Vectores/genética , Mosquitos Vectores/virología , ARN Interferente Pequeño/genética
16.
Cureus ; 16(4): e57603, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38707036

RESUMEN

Background Chikungunya virus (CHIKV) infection poses a significant global health threat, necessitating a deeper understanding of its molecular mechanisms for effective management and treatment. This study aimed to understand the molecular and genetic mechanisms of CHIKV infection by analyzing microarray expression data. Methodology National Center for Biotechnology Information (NCBI) GEO2R with an adjusted p-value cut-off of <0.05 and |log2FC ≥ 1.5| was used to identify the differentially expressed genes involved in CHIKV infection using microarray data from the Gene Expression Omnibus (GEO) database, followed by enrichment analysis, protein-protein interaction (PPI) network construction, and, finally, hub gene identification. Results Analysis of the microarray dataset revealed 25 highly significant differentially expressed genes (DEGs), including 21 upregulated and four downregulated genes. PPI network analysis elucidated interactions among these DEGs, with hub genes such as ACTB and CTNNB1 exhibiting central roles. Enrichment analysis identified crucial pathways, including leukocyte transendothelial migration, regulation of actin cytoskeleton, and thyroid hormone signaling, implicating their involvement in CHIKV infection. Furthermore, the study highlights potential therapeutic targets such as ACTB and CTNNB1, which showed significant upregulation in infected cells. Conclusions These findings underscore the complex interplay between viral infection and host cellular processes, shedding light on novel avenues for diagnostic marker discovery and advancing antiviral strategies. In this study, we shed light on the molecular and genetic mechanisms of CHIKV infection and the potential role of ACTB and CTNNB1 genes.

17.
Rev. salud pública Parag ; 14(1)abr. 2024.
Artículo en Inglés | LILACS-Express | LILACS | ID: biblio-1560415

RESUMEN

Introduction: The rapid transmission and severe symptoms associated with acute chikungunya virus (CHIKV) infection in children make it a highly concerning health issue. Objective: This study aimed to describe the characteristics of acute chikungunya virus infection in children from the Department of Caaguazú, Paraguay. Material and Methods: A retrospective observational study was conducted in the Department of Caaguazú, Paraguay, in 2023, with all patients who came to the Regional Hospital within 5 days of developing characteristic symptoms of acute CHIKV infection and tested positive for the virus by RT-PCR. Patients with Dengue or Zika infections were excluded. We collected data on clinical characteristics using a standardized case record form and created an electronic dataset for analysis. Results: A total of 461 children were included in the study. 51.6% were women. Cases were divided into groups based on pediatric age: infants (0-23 months, n=88, 19.1%), preschoolers (2-5 years, n=115, 24.9%), schoolchildren (6-11 years, n=163, 35.4%), and adolescents (12-17 years and 11 months, n=95, 20.6%). Schoolchildren and adolescents experienced a higher prevalence of myalgia (64.6%) and arthralgia (63.7%). Vomiting (89%), headache (89.4%), and retro-orbital pain (95%) were more common in preschoolers, schoolchildren, and adolescents, while rash (39.5%) and petechiae (18.5%) were more prevalent in infants. Four children died during the study period. Conclusion: The 2023 CHIKV virus epidemic in Paraguay had different clinical presentations depending on the age of the affected children, with fatal outcomes occurring in a small percentage of cases.


Introducción: La rápida transmisión y los síntomas graves asociados con la infección aguda por el virus de la chikungunya (CHIKV) en niños lo convierten en un problema de salud altamente preocupante. Objetivo: Este estudio tuvo como objetivo describir las características de la infección aguda por el virus de la chikungunya en niños del Departamento de Caaguazú, Paraguay. Materiales y métodos: Un estudio retrospectivo fue realizado en el Departamento de Caaguazú, Paraguay, en 2023, con todos los pacientes que acudieron al Hospital Regional dentro de los 5 días posteriores al desarrollo de síntomas característicos de la infección aguda por CHIKV y que dieron positivo para el virus mediante RT-PCR. Pacientes con infecciones por Dengue o Zika fueron excluidos. Se recogieron datos sobre las características clínicas mediante un formulario normalizado de registro de casos y se creó un conjunto de datos electrónicos para su análisis. Resultados: Se incluyeron en el estudio un total de 461 niños. 51,6% eran mujeres. Los casos se dividieron en grupos según la edad pediátrica: lactantes (0-23 meses, n=88, 19,1 %), preescolares (2-5 años, n=115, 24,9%), escolares (6-11 años, n=163, 35.4%), and adolescentes (12-17 años and 11 meses, n=95, 20.6 %). La mialgia (64,6%) y la artralgia (63.7%) fueron más prevalentes en escolares y adolescentes. El vómito (89%), la cefalea (89,4%) y el dolor retroorbitario (95%) fueron más comunes en preescolares, escolares y adolescentes, mientras que la erupción cutánea (39,5%) y las petequias (18,5%) fueron más prevalentes en lactantes. Cuatro niños fallecieron durante el período de estudio. Conclusión: La epidemia de virus de la CHIKV de 2023 en Paraguay tuvo diferentes presentaciones clínicas dependiendo de la edad de los niños afectados, con resultados fatales ocurriendo en un pequeño porcentaje de casos.

18.
Asia Pac J Public Health ; 36(5): 504-510, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38641958

RESUMEN

As Chikungunya virus (CHIKV) infection continues to rise globally, including in Malaysia, it is essential for healthcare workers (HCWs) to have adequate knowledge about the disease for diagnostic accuracy and to improve public health surveillance systems. This study aimed to assess awareness and measure the level of knowledge of CHIKV infection among HCWs in the Hulu Langat district and explore associated sociodemographic and skill-related factors. This was a cross-sectional study in which the questionnaire was physically distributed to participants using the universal sampling method. All participants (100%) were aware of CHIKV infection, and most (80.1%) had knowledge of the disease. Furthermore, networks such as professional members, family, and friends (27.8%), followed by professional development programs (23.1%), were identified as the common platforms utilized by HCWs to access information regarding CHIKV infection. Ordinal logistic regression analysis further demonstrated that the level of education (odds ratio [OR] = 2.23,) and HCWs who attended Continuing Medical Education (CME)/courses on CHIKV infection (OR = 1.73,) and had experience in handling the case (OR = 3.23,) were significantly associated with awareness and knowledge of the disease. Implementing continuous education and training can enhance HCWs' understanding of CHIKV infection.


Asunto(s)
Fiebre Chikungunya , Conocimientos, Actitudes y Práctica en Salud , Personal de Salud , Humanos , Malasia/epidemiología , Estudios Transversales , Fiebre Chikungunya/epidemiología , Masculino , Femenino , Adulto , Personal de Salud/psicología , Personal de Salud/estadística & datos numéricos , Persona de Mediana Edad , Adulto Joven , Encuestas y Cuestionarios
19.
Braz J Infect Dis ; 28(2): 103741, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38670165

RESUMEN

Sickle Cell Disease (SCD) is a hereditary disease characterized by extravascular and intravascular hemolysis and clinical variability, from mild pain to potentially life-threatening. Arboviruses include mainly Zika (ZIKV), Chikungunya (CHKV), and Dengue (DENV) virus, and are considered a public and social health problem. The present cross-sectional observational study aimed to investigate the prevalence of arbovirus infection in SCD patients from two Brazilian cities, Salvador and Manaus located in Bahia and Amazonas states respectively. A total of 409 individuals with SCD were included in the study, and 307 (75.06 %) patients tested positive for DENV-IgG, 161 (39.36 %) for ZIKV-IgG, and 60 (14.67 %) for CHIKV-IgG. Only one individual was positive for DENV-NS1 and another for DENV-IgM, both from Salvador. No individuals had positive serology for ZIKV-IgM or CHIKV-IgM. Arbovirus positivity by IgG testing revealed that the SCD group presented high frequencies in both cities. Interestingly, these differences were only statistically significant for ZIKV-IgG (p = 0.023) and CHIKV-IgG (p = 0.005) among SCD patients from Manaus. The reshaping of arbovirus from its natural habitat by humans due to disorderly urban expansion and the ease of international Mobility has been responsible for facilitating the spread of vector-borne infectious diseases in humans. We found the need for further studies on arboviruses in this population to elucidate the real association and impact, especially in acute infection. We hope that this study will contribute to improvements in the personalized clinical follow-up of SCD patients, identifying the influence of arbovirus infection in severe disease manifestations.


Asunto(s)
Anemia de Células Falciformes , Infecciones por Arbovirus , Arbovirus , Humanos , Brasil/epidemiología , Anemia de Células Falciformes/epidemiología , Anemia de Células Falciformes/complicaciones , Estudios Transversales , Masculino , Femenino , Adulto , Prevalencia , Infecciones por Arbovirus/epidemiología , Infecciones por Arbovirus/virología , Adulto Joven , Adolescente , Arbovirus/aislamiento & purificación , Inmunoglobulina G/sangre , Niño , Infección por el Virus Zika/epidemiología , Infección por el Virus Zika/complicaciones , Anticuerpos Antivirales/sangre , Persona de Mediana Edad , Dengue/epidemiología , Inmunoglobulina M/sangre , Virus del Dengue/inmunología , Virus Zika/inmunología , Virus Zika/aislamiento & purificación , Preescolar , Fiebre Chikungunya/epidemiología , Fiebre Chikungunya/complicaciones
20.
Front Epidemiol ; 4: 1342723, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38456075

RESUMEN

Arthropod-borne viral diseases are likely to be affected by the consequences of climate change with an increase in their distribution and intensity. Among these infectious diseases, chikungunya and dengue viruses are two (re)emergent arboviruses transmitted by Aedes species mosquitoes and which have recently demonstrated their capacity for rapid expansion. They most often cause mild diseases, but they can both be associated with complications and severe forms. In Europe, following the establishment of invasive Aedes spp, the first outbreaks of autochtonous dengue and chikungunya have already occurred. Northern Europe is currently relatively spared, but climatic projections show that the conditions are permissive for the establishment of Aedes albopictus (also known as the tiger mosquito) in the coming decades. It is therefore essential to question and improve the means of surveillance in northern Europe, at the dawn of inevitable future epidemics.

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