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BACKGROUND: Currently, there is no antiviral licensed to treat chikungunya fever, a disease caused by the infection with Alphavirus chikungunya (CHIKV). Treatment is based on analgesic and anti-inflammatory drugs to relieve symptoms. Our study aimed to evaluate the antiviral activity of sulfadoxine (SFX), an FDA-approved drug, and its derivatives complexed with silver(I) (AgSFX), salicylaldehyde Schiff base (SFX-SL), and with both Ag and SL (AgSFX-SL) against CHIKV. METHODS: The anti-CHIKV activity of SFX and its derivatives was investigated using BHK-21 cells infected with CHIKV-nanoluc, a marker virus-carrying nanoluciferase reporter. Dose-response and time of drug-addition assays were performed in order to assess the antiviral effects of the compounds, as well as in silico data and ATR-FTIR analysis for insights on their mechanisms of action. RESULTS: The SFX inhibited 34% of CHIKV replication, while AgSFX, SFX-SL, and AgSFX-SL enhanced anti-CHIKV activity to 84%, 89%, and 95%, respectively. AgSFX, SFX-SL, and AgSFX-SL significantly decreased viral entry and post-entry to host cells, and the latter also protected cells against infection. Additionally, molecular docking calculations and ATR-FTIR analysis demonstrated interactions of SFX-SL, AgSFX, and AgSFX-SL with CHIKV. CONCLUSIONS: Collectively, our findings suggest that the addition of metal ions and/or Schiff base to SFX improved its antiviral activity against CHIKV.
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Antivirais , Febre de Chikungunya , Vírus Chikungunya , Sulfadoxina , Vírus Chikungunya/efeitos dos fármacos , Antivirais/farmacologia , Antivirais/química , Animais , Linhagem Celular , Sulfadoxina/farmacologia , Febre de Chikungunya/tratamento farmacológico , Febre de Chikungunya/virologia , Cricetinae , Bases de Schiff/farmacologia , Prata/farmacologia , Prata/química , Replicação Viral/efeitos dos fármacos , Simulação de Acoplamento Molecular , Relação Dose-Resposta a Droga , Humanos , AldeídosRESUMO
Dengue (DENV) and Chikungunya (CHIKV) viruses can be transmitted simultaneously by Aedes mosquitoes, and there may be co-infections in humans. However, how the adaptive immune response is modified in the host has yet to be known entirely. In this study, we analyzed the cross-reactivity and neutralizing activity of IgG antibodies against DENV and CHIKV in sera of patients from the Mexican Institute of Social Security in Veracruz, Mexico, collected in 2013 and 2015 and using IgG antibodies of BALB/c mice inoculated with DENV and/or CHIKV. Mice first inoculated with DENV and then with CHIKV produced IgG antibodies that neutralized both viruses. Mice were inoculated with CHIKV, and then with DENV; they had IgG antibodies with more significant anti-CHIKV IgG antibody neutralizing activity. However, the inoculation only with CHIKV resulted in better neutralization of DENV2. In sera obtained from patients in 2013, significant cross-reactivity and low anti-CHIKV IgG antibody neutralizing activity were observed. In CHIKV-positive 2015 sera, the anti-DENV IgG antibody neutralizing activity was high. These results suggest that CHIKV stimulates DENV2-induced memory responses and vice versa. Furthermore, cross-reactivity between the two viruses generated neutralizing antibodies, but exchanging CHIKV for DENV2 generated a better anti-CHIKV neutralizing response.
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Anticorpos Neutralizantes , Anticorpos Antivirais , Febre de Chikungunya , Vírus Chikungunya , Reações Cruzadas , Vírus da Dengue , Dengue , Imunoglobulina G , Camundongos Endogâmicos BALB C , Animais , Vírus Chikungunya/imunologia , Anticorpos Neutralizantes/imunologia , Anticorpos Neutralizantes/sangue , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Anticorpos Antivirais/imunologia , Anticorpos Antivirais/sangue , Dengue/imunologia , Dengue/virologia , Vírus da Dengue/imunologia , Humanos , Febre de Chikungunya/imunologia , Febre de Chikungunya/virologia , Reações Cruzadas/imunologia , Camundongos , México , Feminino , Testes de Neutralização , Masculino , Coinfecção/imunologia , Coinfecção/virologia , AdultoRESUMO
Although the disease caused by chikungunya virus (CHIKV) is of great interest to public health organizations around the world, there are still no authorized antivirals for its treatment. Previously, dihalogenated anti-CHIKV compounds derived from L-tyrosine (dH-Y) were identified as being effective against in vitro infection by this virus, so the objective of this study was to determine the mechanisms of its antiviral action. Six dH-Y compounds (C1 to C6) dihalogenated with bromine or chlorine and modified in their amino groups were evaluated by different in vitro antiviral strategies and in silico tools. When the cells were exposed before infection, all compounds decreased the expression of viral proteins; only C4, C5 and C6 inhibited the genome; and C1, C2 and C3 inhibited infectious viral particles (IVPs). Furthermore, C1 and C3 reduce adhesion, while C2 and C3 reduce internalization, which could be related to the in silico interaction with the fusion peptide of the E1 viral protein. Only C3, C4, C5 and C6 inhibited IVPs when the cells were exposed after infection, and their effect occurred in late stages after viral translation and replication, such as assembly, and not during budding. In summary, the structural changes of these compounds determine their mechanism of action. Additionally, C3 was the only compound that inhibited CHIKV infection at different stages of the replicative cycle, making it a compound of interest for conversion as a potential drug.
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Antivirais , Febre de Chikungunya , Vírus Chikungunya , Tirosina , Replicação Viral , Vírus Chikungunya/efeitos dos fármacos , Vírus Chikungunya/fisiologia , Tirosina/farmacologia , Tirosina/análogos & derivados , Tirosina/metabolismo , Tirosina/química , Antivirais/farmacologia , Antivirais/química , Febre de Chikungunya/tratamento farmacológico , Febre de Chikungunya/virologia , Animais , Replicação Viral/efeitos dos fármacos , Chlorocebus aethiops , Células Vero , Humanos , Internalização do Vírus/efeitos dos fármacos , Proteínas Virais/metabolismoRESUMO
Chikungunya, arbovirose que provoca febre e artralgia debilitante, demonstra potencial crônico e incapacitante por longos períodos, não havendo vacinas ou terapias específicas. Recentemente, a doença evoluiu da condição negligenciada para uma ameaça à saúde pública, impactando milhões de pessoas em regiões tropicais e subtropicais. Este estudo analisa a produção do conhecimento sobre a Chikungunya, na perspectiva da Vigilância em Saúde. Trata-se de metodologia exploratória-descritiva, com análise bibliométrica. Realizou-se a coleta nas bases Scopus e Web of Science para artigos de 2008 a 2022. A análise revelou uma série temporal de produção destacando a contribuição de Estados Unidos, Brasil e França. Identificaram-se como áreas mais produtivas: doenças transmissíveis, medicina tropical e parasitologia, fundamentais à Vigilância em Saúde e ao planejamento de políticas públicas. Quanto aos pesquisadores, Weaver, Scott C., Failloux, Anna-Bella e De Lamballerie, Xavier foram relevantes no cenário global, indicando a importância da colaboração e da abordagem interdisciplinar.
Chikungunya, an arbovirus that causes fever and debilitating arthralgia, has potential to be chronic and incapacitating for long periods, and there are no vaccines or therapies available for it. Recently, the disease has evolved from a neglected condition to public health threat, impacting millions in tropical and subtropical regions. This study analyzed the knowledge production about chikungunya, from the perspective of Health Surveillance, using an exploratory-descriptive methodology and bibliometric analysis. Articles from 2008 to 2022 were collected from Scopus and Web of Science databases. The analysis showed a production time series, highlighting the contribution of United States, Brazil, and France. The most productive areas were identified as: communicable diseases, tropical medicine and parasitology, which are fundamental to Health Surveillance and public policy planning. Regarding researchers, Weaver, Scott C., Failloux, Anna-Bella, and De Lamballerie, Xavier were relevant in the global scenario, indicating the importance of collaboration and of the interdisciplinary approach.
El chikungunya, arbovirus que causa fiebre y artralgia debilitante, tiene potencial de ser crónico e incapacitante por largos periodos, todavía no hay vacunas ni terapias. Recientemente, la enfermedad ha pasado de afección desatendida a amenaza para la salud pública, afectando a millones en regiones tropicales y subtropicales. Este estudio analiza la producción de conocimientos sobre chikungunya, desde la perspectiva de la Vigilancia Sanitaria. Se utilizó una metodología exploratoria-descriptiva con análisis bibliométrico. Se recompilaron artículos de Scopus y Web of Science, 2008-2022. El análisis reveló una serie temporal de producción, destacando la contribución de EEUU, Brasil y Francia. Se identificaron como áreas más productivas: enfermedades transmisibles, medicina tropical y parasitología, fundamentales para la Vigilancia Sanitaria y la planificación de políticas públicas. En cuanto a los investigadores, Weaver, Scott C., Failloux, Anna-Bella y De Lamballeire, Xavier fueron relevantes en el escenario global, indicando la importancia de la colaboración y del enfoque interdisciplinario.
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Epidemiologia , Bibliometria , Vírus Chikungunya , Atividades Científicas e Tecnológicas , Comunicação em Saúde , Política de Saúde , Infecções por Arbovirus , Vigilância Sanitária , Saúde Pública , Doenças Transmissíveis , Vigilância em Saúde PúblicaRESUMO
Chikungunya virus (CHIKV) is transmitted by mosquito bites and causes chikungunya fever (CHIKF). CHIKV has a single-stranded RNA genome and belongs to a single serotype with three genotypes. The Asian lineage has recently emerged in the Western Hemisphere, likely due to travel-associated introduction. Genetic variation accumulates in the CHIKV genome as the virus replicates, creating new lineages. Whole genome sequencing is ideal for studying virus evolution and spread but is expensive and complex. This study investigated whether specific, highly variable regions of the CHIKV genome could recapitulate the phylogeny obtained with a complete coding sequence (CDS). Our results revealed that concatenated highly variable regions accurately reconstructed CHIKV phylogeny, exhibiting statistically indistinguishable branch lengths and tree confidence compared to CDS. In addition, these regions adequately inferred the evolutionary relationships among CHIKV isolates from the American outbreak with similar results to the CDS. This finding suggests that highly variable regions can effectively capture the evolutionary relationships among CHIKV isolates, offering a simpler approach for future studies. This approach could be particularly valuable for large-scale surveillance efforts.
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Febre de Chikungunya , Vírus Chikungunya , Variação Genética , Genoma Viral , Filogenia , Vírus Chikungunya/genética , Vírus Chikungunya/classificação , Vírus Chikungunya/isolamento & purificação , Febre de Chikungunya/virologia , Humanos , Genótipo , Sequenciamento Completo do Genoma/métodos , Evolução Molecular , Genômica/métodos , Fases de Leitura Aberta , Animais , RNA Viral/genéticaRESUMO
Chikungunya virus (Togaviridae, Alphavirus; CHIKV) is a mosquito-borne global health threat. The main urban vector of CHIKV is the Aedes aegypti mosquito, which is found throughout Brazil. Therefore, it is important to carry out laboratory tests to assist in the virus's diagnosis and surveillance. Most molecular biology methodologies use nucleic acid extraction as the first step and require quality RNA for their execution. In this context, four RNA extraction protocols were evaluated in Ae. aegypti experimentally infected with CHIKV. Six pools were tested in triplicates (n = 18), each containing 1, 5, 10, 20, 30, or 40 mosquitoes per pool (72 tests). Four commercial kits were compared: QIAamp®, Maxwell®, PureLink®, and PureLink® with TRIzol®. The QIAamp® and PureLink® with TRIzol® kits had greater sensitivity. Two negative correlations were observed: as the number of mosquitoes per pool increases, the Ct value decreases, with a higher viral load. Significant differences were found when comparing the purity and concentration of RNA. The QIAamp® protocol performed better when it came to lower Ct values and higher RNA purity and concentration. These results may provide help in CHIKV entomovirological surveillance planning.
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Aedes , Febre de Chikungunya , Vírus Chikungunya , Mosquitos Vetores , RNA Viral , Vírus Chikungunya/isolamento & purificação , Vírus Chikungunya/genética , Aedes/virologia , Animais , RNA Viral/isolamento & purificação , RNA Viral/genética , Mosquitos Vetores/virologia , Febre de Chikungunya/virologia , Febre de Chikungunya/diagnóstico , Carga Viral/métodosRESUMO
Chikungunya disease typically presents with the fever-arthralgia-rash symptom triad. However, an increase in the number of atypical clinical manifestations, particularly neurological disorders, has occurred. The current evidence regarding the pooled prevalence of Chikungunya virus (CHIKV)-associated neurological cases (CANCs) suspected of having an arboviral aetiology is not well-understood. Therefore, this meta-analysis included 19 studies (n = 7319 patients) and aimed to determine the pooled rate of exposure to CANC. The pooled positivity rate of CANC was 12 % (95 % CI: 6-19), and Brazil was overrepresented (11/19). These estimations varied between 3 and 14 % based on the diagnostic method (real-time PCR vs. ELISA-IgM) and biological samples (cerebrospinal fluid or blood specimens) used for detection of CHIKV. Regarding the frequency of CHIKV in neurological clinical subgroups, the rates were higher among patients with myelitis (27 %), acute disseminated encephalomyelitis (27 %), Guillain-Barré syndrome (15 %), encephalitis (12 %), and meningoencephalitis (7 %). Our analysis highlights the significant burden of CANC. However, the data must be interpreted with caution due to the heterogeneity of the results, which may be related to the location of the studies covering endemic periods and/or outbreaks of CHIKV. Current surveillance resources should also focus on better characterizing the epidemiology of CHIKV infection in neurological disorders. Additionally, future studies should investigate the interactions between CHIKV and neurological diseases with the aim of gaining deeper insight into the mechanisms underlying the cause-and-effect relationship between these two phenomena.
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Febre de Chikungunya , Vírus Chikungunya , Síndrome de Guillain-Barré , Doenças do Sistema Nervoso , Humanos , Brasil/epidemiologia , Febre de Chikungunya/epidemiologia , Febre de Chikungunya/diagnóstico , Vírus Chikungunya/isolamento & purificação , Encefalomielite Aguda Disseminada/epidemiologia , Encefalomielite Aguda Disseminada/virologia , Síndrome de Guillain-Barré/epidemiologia , Síndrome de Guillain-Barré/virologia , Meningoencefalite/epidemiologia , Meningoencefalite/virologia , Mielite/epidemiologia , Mielite/virologia , Doenças do Sistema Nervoso/epidemiologia , Doenças do Sistema Nervoso/virologia , PrevalênciaRESUMO
INTRODUCTION: Chikungunya fever is a disease caused by infection with the Chikungunya virus, transmitted by Aedes aegypti and Aedes albopictus mosquitoes. Despite its self-limited character, more than 60% of patients have chronic recurrent arthralgia with debilitating pain that lasts for years. AIM: The objective of this review was to gather and analyze evidence from the literature on potential therapeutic strategies with molecules from natural products for the treatment of Chikungunya fever. METHODS: A search was performed for clinical trials, observational studies, in vitro or in vivo, without restriction of the year of publication or language in electronic databases (Medline/PubMed, EMBASE, Google Scholar, The Cochrane Library, LILACS (BVS), clinical trial registries (Clinical Trials.gov), digital libraries from CAPES theses and dissertations (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Brazil) and conference abstracts. A quality assessment of the selected studies was performed using the SYRCLE, RoB2 and SciRAP tools. RESULTS: 42 studies were included, which showed molecules with potential antiviral pharmacological activity or with activity in reducing the joint complications caused by CHIKV infection. CONCLUSIONS: Among the molecules found in the survey of references, regarding the class of secondary metabolites, flavonoids stood out and for this reason, the molecules may be promising candidates for future clinical trials. Overall, evidence from in vitro studies was of acceptable quality; in vivo and intervention studies showed a high risk of bias, which is a limitation of these studies.
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Antivirais , Produtos Biológicos , Febre de Chikungunya , Vírus Chikungunya , Febre de Chikungunya/tratamento farmacológico , Humanos , Produtos Biológicos/uso terapêutico , Produtos Biológicos/farmacologia , Antivirais/farmacologia , Antivirais/uso terapêutico , Animais , Vírus Chikungunya/efeitos dos fármacos , Ensaios Clínicos como AssuntoRESUMO
We aimed to describe the landscape, including molecular, epidemiological, and clinical aspects of CHIKV infections in the Ribeirao Preto region, an area endemic to dengue. We randomly screened 3744 plasma samples that had undergone DENV diagnosis to evaluate CHIKV-RNA using an in-house RT-PCR assay. Positive samples were followed clinically, and RNA samples were submitted to whole genome sequencing. Seventeen cases (0.5 %) were positive for CHIKV-RNA despite being negative for DENV-RNA. Notably, half of the patients experienced prolonged arthralgia lasting more than 90 days. Compared with the healthy control group, leukopenia and thrombocytopenia were observed in all CHIKV-positive individuals with statistically significant P values (P < 0.0001 and P = 0.0003, respectively). The genomic analysis revealed that the CHIKV strains being studied are classified within the East-Central-South-African (ECSA) genotype. This analysis identified new mutations, E1: K211E and E2: V264A, while the previously known mutation E1: A226V was not detected among these strains. This study highlights the need for epidemiological surveillance and preparedness for potential CHIKV epidemics in Brazil, particularly where other arboviruses co-circulate.
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Febre de Chikungunya , Vírus Chikungunya , Dengue , Genótipo , RNA Viral , Humanos , Brasil/epidemiologia , Febre de Chikungunya/epidemiologia , Febre de Chikungunya/sangue , Febre de Chikungunya/virologia , Vírus Chikungunya/genética , Vírus Chikungunya/isolamento & purificação , Dengue/epidemiologia , Dengue/virologia , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , RNA Viral/genética , Adulto Jovem , Doenças Endêmicas , Adolescente , Sequenciamento Completo do Genoma , Idoso , Criança , Filogenia , Mutação , Pré-Escolar , Vírus da Dengue/genética , Vírus da Dengue/isolamento & purificação , Vírus da Dengue/classificação , Trombocitopenia/epidemiologia , Trombocitopenia/virologiaRESUMO
Objective: Arboviruses pose a challenge in ensuring the supply of pathogen-free blood components because they are not routinely screened in blood banks, and blood components from infected asymptomatic donors could be transfused. This study aimed to detect and characterize arboviral infections in Colombian blood donors. Methods: In a cross-sectional study, the prevalence of dengue (DENV), Zika (ZIKV), and chikungunya (CHIKV) viruses and co-infections of blood donors were compared between an epidemic period (November 2019-February 2020, n = 462) and an endemic period (November 2021-August 2022, n = 1,119). Viral RNA from each donor serum was purified, and the viruses were detected using a previously standardized multiplex hemi-nested RT-PCR protocol. Subsequently, donors who tested positive were surveyed 15 days after the detection of the virus to identify clinical characteristics related to the arboviral infection. The prevalences of each virus were presented as percentages and compared between epidemic and endemic periods. Results: Significantly higher prevalences were found in the epidemic period compared with the endemic period for DENV (14.5 vs. 1.9%), ZIKV (7.8 vs. 0.3%), CHIKV (8 vs. 3.3%), and co-infections (4.3 vs. 0.2%). The survey response rate of positive donors in the two periods was 83/175 (47%). In total, 57% of the donors surveyed were asymptomatic. Symptomatic donors most frequently reported headache (31%), malaise (13%), arthralgia (10%), and fever/chills (8%). Conclusion: The prevalence observed in epidemic and endemic periods was higher than that reported in other studies in the Americas. The high proportion of asymptomatic cases found, in addition to the mild and nonspecific manifestations among the symptomatic, may limit the effectiveness of the donor selection criteria used to mitigate the risk of transfusion-transmitted arboviruses.
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Background: Dengue virus (DENV) and Chikungunya virus (CHIKV) pose significant public health threats in Brazil, where favorable conditions facilitated the proliferation of Aedes mosquitoes. Since the mid-1980s, Brazil has experienced annual outbreaks of DENV, with recent increases in confirmed cases. In addition, CHIKV, which was first reported in 2014, has spread across the country. The concurrent presence of these viruses has triggered public health alerts in endemic regions, underscoring the complexity of managing vector-borne diseases. Case Presentation: This report details a case of simultaneous DENV and CHIKV infections. A 77-year-old female patient who has diabetes and arrhythmia exhibited symptoms including fever, myalgia, and severe arthralgia. Laboratory tests confirmed the coinfection through RNA detection. The patient received supportive care, showed gradual improvement, and was eventually discharged. Conclusions: Coinfection with DENV and CHIKV cases reported here developed with mild outcomes. However, one of the patients did not recover from the arthralgia after presenting diagnostic challenges, which underscores the need for accurate differentiation to manage symptoms effectively. The reported cases, amidst increasing DENV outbreaks, highlight the urgency for preparedness in the healthcare system. The Ribeirão Preto region's endemicity for DENV, coupled with the rising incidence of CHIKV, emphasizes the evolving landscape of arbovirus transmission. Studies on Aedes mosquitoes suggest potential implications for human infection dynamics, warranting further investigation into arbovirus transmission efficacy and coinfection dynamics.
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Introducción: El virus chikungunya (CHIKV) causa una enfermedad con manifestaciones agudas bien documentadas, pero existen pocos datos sobre la persistencia de síntomas y secuelas a largo plazo. Objetivos: Evaluar la persistencia de signos, síntomas y factores asociados en pacientes con infección por CHIKV en un seguimiento de 6 meses posinfección. Materiales y métodos: Estudio de cohorte ambispectivo que incluyó casos confirmados de CHIKV notificados en abril de 2023 en Coronel Oviedo, Paraguay. Se realizaron entrevistas al mes, a los tres meses y a los 6 meses posinfección. Se analizaron características demográficas, comorbilidades, manifestaciones reumáticas y sintomáticas. Resultados: Ingresaron 333 participantes, completando seguimiento a 6 meses 170 pacientes. A los 6 meses persistieron: dolor de espalda (61.2%), artritis (57.1%), cefalea (54.1%), fatiga (51.2%), mialgia (49.4%), debilidad (47.6%), depresión (45.9%) y artralgia (45.9%). La persistencia de artritis (OR 7.54; p=0.008) y mialgia (OR 3.24; p=0.031) a 6 meses fue mayor en el grupo de 36-45 años. Conclusiones: Alta persistencia de síntomas musculoesqueléticos y fatiga hasta 6 meses posinfección, con tendencia decreciente, pero exacerbación de depresión. Edad entre 36-45 años asociada a mayor persistencia. Se requieren protocolos de seguimiento integral, investigar mecanismos fisiopatológicos y fortalecer prevención, dado el impacto individual y socioeconómico de la enfermedad.
Introduction: Chikungunya virus (CHIKV) causes a disease with well-documented acute manifestations, but there is limited data on the persistence of symptoms and long-term sequelae. Objectives: To evaluate the persistence of signs, symptoms, and associated factors in patients with CHIKV infection during a 6-month post-infection follow-up. Material and Methods: An ambispective cohort study that included confirmed cases of CHIKV reported in April 2023 in Coronel Oviedo, Paraguay. Interviews were conducted at 1, 3 and 6 months post-infection. Demographic characteristics, comorbidities, rheumatic, and symptomatic manifestations were analyzed. Results: 333 participants were enrolled, with 170 patients completing the 6-month follow-up. At 6 months, the following symptoms persisted: back pain (61.2%), arthritis (57.1%), headache (54.1%), fatigue (51.2%), myalgia (49.4%), weakness (47.6%), depression (45.9%), and arthralgia (45.9%). The persistence of arthritis (OR 7.54, p=0.008) and myalgia (OR 3.24, p=0.031) at 6 months was higher in the 36-45 age group. Conclusions: High persistence of musculoskeletal symptoms and fatigue up to 6 months post-infection, with a decreasing trend but exacerbation of depression. Age between 36-45 years was associated with greater persistence. Comprehensive follow-up protocols, investigation of pathophysiological mechanisms, and strengthening prevention are required, given the individual and socioeconomic impact of the disease.
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The incidence of chikungunya has dramatically surged worldwide in recent decades, imposing an expanding burden on public health. In recent years, South America, particularly Brazil, has experienced outbreaks that have ravaged populations following the rapid dissemination of the chikungunya virus (CHIKV), which was first detected in 2014. The primary vector for CHIKV transmission is the urban mosquito species Aedes aegypti, which is highly prevalent throughout Brazil. However, the impact of the locally circulating CHIKV genotypes and specific combinations of local mosquito populations on vector competence remains unexplored. Here, we experimentally analyzed and compared the infectivity and transmissibility of the CHIKV-ECSA lineage recently isolated in Brazil among four Ae. aegypti populations collected from different regions of the country. When exposed to CHIKV-infected AG129 mice for blood feeding, all the mosquito populations displayed high infection rates and dissemination efficiency. Furthermore, we observed that all the populations were highly efficient in transmitting CHIKV to a vertebrate host (naïve AG129 mice) as early as eight days post-infection. These results demonstrate the high capacity of Brazilian Ae. aegypti populations to transmit the locally circulating CHIKV-ECSA lineage. This observation could help to explain the high prevalence of the CHIKV-ECSA lineage over the Asian lineage, which was also detected in Brazil in 2014. However, further studies comparing both lineages are necessary to gain a better understanding of the vector's importance in the epidemiology of CHIKV in the Americas.
Assuntos
Aedes , Febre de Chikungunya , Vírus Chikungunya , Mosquitos Vetores , Animais , Aedes/virologia , Vírus Chikungunya/genética , Vírus Chikungunya/classificação , Vírus Chikungunya/fisiologia , Vírus Chikungunya/isolamento & purificação , Brasil/epidemiologia , Febre de Chikungunya/transmissão , Febre de Chikungunya/virologia , Febre de Chikungunya/epidemiologia , Camundongos , Mosquitos Vetores/virologia , Genótipo , Feminino , FilogeniaRESUMO
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.
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Vírus Chikungunya , Vírus Chikungunya/genética , Uruguai/epidemiologia , América/epidemiologia , Surtos de Doenças , GenômicaRESUMO
Arthritis and periodontitis are inflammatory diseases that share several immunopathogenic features. The expansion in the study of virus-induced arthritis has shed light on how this condition could impact other parts of the human body, including the mouth. Viral arthritis is an inflammatory joint disease caused by several viruses, most notably the alphaviruses Chikungunya virus (CHIKV), Sindbis virus (SINV), Ross River virus (RRV), Mayaro virus (MAYV), and O'nyong'nyong virus (ONNV). These viruses can induce an upsurge of matrix metalloproteinases and immune-inflammatory mediators such as Interleukin-6 (IL6), IL-1ß, tumor necrosis factor, chemokine ligand 2, and receptor activator of nuclear factor kappa-B ligand in the joint and serum of infected individuals. This can lead to the influx of inflammatory cells to the joints and associated muscles as well as osteoclast activation and differentiation, culminating in clinical signs of swelling, pain, and bone resorption. Moreover, several data indicate that these viral infections can affect other sites of the body, including the mouth. The human oral cavity is a rich and diverse microbial ecosystem, and viral infection can disrupt the balance of microbial species, causing local dysbiosis. Such events can result in oral mucosal damage and gingival bleeding, which are indicative of periodontitis. Additionally, infection by RRV, CHIKV, SINV, MAYV, or ONNV can trigger the formation of osteoclasts and upregulate pro-osteoclastogenic inflammatory mediators, interfering with osteoclast activation. As a result, these viruses may be linked to systemic conditions, including oral manifestations. Therefore, this review focuses on the involvement of alphavirus infections in joint and oral health, acting as potential agents associated with oral mucosal inflammation and alveolar bone loss. The findings of this review demonstrate how alphavirus infections could be linked to the comorbidity between arthritis and periodontitis and may provide a better understanding of potential therapeutic management for both conditions.
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Infecções por Alphavirus , Artrite , Vírus Chikungunya , Periodontite , Humanos , Infecções por Alphavirus/tratamento farmacológico , Infecções por Alphavirus/patologia , Vírus Chikungunya/fisiologia , Mediadores da Inflamação/uso terapêutico , Ligantes , Ross River virus/fisiologiaRESUMO
Arboviruses cause public health problems in several countries, and records show that they can generate central and peripheral neurological complications with permanent sequelae. However, it is not certain which arbovirus is responsible for outbreaks of the Guillain-Barré Syndrome (GBS), especially in Brazil. Thus, the objective of this study is to verify if there is a coincidence between the GBS outbreak and the most common arboviruses in Northeastern Brazil, as well as their relationship. An ecological time series study was designed with the federative units of Northeastern Brazil, using hospitalizations for Guillain-Barré syndrome and notifications of arbovirus infections between 2014 and 2019 as a data source. Distribution incidence curves were constructed for the conditions studied, and generalized estimating equations (GEE) models were applied to estimate the relationship between arboviruses and Guillain-Barré. The results showed a similar distribution for the incidences of Chikungunya virus (z=7.82; p=0.001), Zika virus (z=3.69; p=0.03), and Guillain-Barré syndrome (z=2.98; p=0.05) from 2014 to 2019. The GEE model revealed that the distribution of Chikungunya incidence is associated with the distribution of GBS incidence in each year (x2Wald=3,969; p=0.046). This pattern was repeated in seven of the nine states, while the Zika virus had a significant relationship with GBS in only two states. The outbreak of GBS in Northeastern Brazil appears to be probabilistically related to outbreaks of the Chikungunya virus.
As arboviroses são problemas de saúde pública em vários países e há registros de que podem produzir complicações neurológicas centrais e periféricas com sequelas permanentes. Entretanto, não se sabe ao certo qual delas é realmente responsável pelos surtos da Síndrome de Guillain-Barré (SGB), principalmente no Brasil. Assim, o objetivo é verificar se há coincidência entre o surto de SGB e as arboviroses mais comuns no Nordeste do Brasil e suas relações. Foi desenhado um estudo ecológico de série temporal com as unidades federativas do Nordeste do Brasil, adotando como fonte de dados as internações Guillain-Barré e as notificações de infecções por arbovírus entre 2014 e 2019. Curvas de distribuição de incidência foram construídas para as condições estudadas, e foram aplicados modelos de equações generalizadas estimadas (GEE) para estimar a relação entre arbovírus e Guillain-Barré. Evidencia-se que há distribuição semelhante para as incidências do vírus Chikungunya (z=7,82; p=0,001), vírus Zika (z=3,69; p=0,03) e síndrome de Guillain-Barré (z=2,98; p=0,05) entre 2014 e 2019. O modelo GEE revelou que a distribuição da incidência de Chikungunya está associada à distribuição da incidência de SGB em cada ano (x2Wald=3,969; p=0,046). Esse padrão se repetiu em sete dos nove estados, enquanto o zika vírus teve uma relação significativa com o GBS em apenas dois estados. Conclui-se, então, que o surto de SGB no Nordeste do Brasil parece estar probabilisticamente relacionado aos surtos do vírus Chikungunya.
Los arbovirus causan problemas de salud pública en varios países y, según indican los reportes, pueden producir complicaciones neurológicas centrales y periféricas con secuelas permanentes. Sin embargo, no se sabe cuál de ellos es realmente el responsable de los brotes del síndrome de Guillain-Barré (SGB), especialmente en Brasil. Así, el objetivo de este estudio es verificar si existen coincidencias entre el brote del SGB y los arbovirus más comunes en el Noreste de Brasil y sus asociaciones. Se diseñó un estudio de series temporales ecológico en las unidades federativas del Noreste de Brasil, adoptando como fuente de datos las hospitalizaciones y las notificaciones de arbovirosis de Guillain-Barré entre 2014 y 2019. Se construyeron curvas de distribución de incidencia para las condiciones científicas, y se aplicó una ecuación estimada generalizada (GEE) para estimar la relación entre arbovirus y Guillain-Barré. Se encontró que existe una distribución similar en las incidencias de virus del chikunguña (z=7,82; p=0,001), virus del Zika (z=3,69; p=0,03) y síndrome de Guillain-Barré (z =2,98; p=0,05) entre 2014 y 2019. El modelo GEE reveló que la distribución de la incidencia de chikunguña está asociada con la distribución de la incidencia de SGB en cada año (x2Wald=3,969; p=0,046). Este patrón se repitió en siete de los nueve estados, mientras que el virus del Zika presentó una relación significativa con el SGB en solo dos estados. El brote del SGB en el Noreste de Brasil parece estar relacionado probabilísticamente con los brotes del virus del chikunguña.
RESUMO
OBJECTIVES: To identify and understand the evidence regarding hearing changes related to acquired Dengue, Chikungunya, and Zika virus infection in adult individuals. METHODS: A scoping review was performed according to the recommendations of The Joanna Briggs Institute and guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews in the Embase, PubMed/Medline, ScienceDirect, Scopus, and Web of Science databases without restriction on language and year of publication. Case studies, observational studies, and clinical trials reporting hearing loss in adult subjects (>18-60 years of age) of both sexes with DENV, CHIKV, or ZIKV diagnosed by positive molecular/serological examination by RT-PCR or IgM/IgG by ELISA method were included. RESULTS: Thirteen studies met the inclusion criteria and were selected for review. The occurrence of auditory symptoms caused by arboviroses and the presence of permanent or transient sensorineural hearing loss was variable in adults. CONCLUSIONS: Dengue, Chikungunya, and Zika infections in adults are associated with a variety of auditory symptoms. The frequency of permanent or transient sensorineural hearing loss is low but not negligible.
Assuntos
Febre de Chikungunya , Vírus Chikungunya , Coinfecção , Vírus da Dengue , Dengue , Perda Auditiva Neurossensorial , Perda Auditiva , Infecção por Zika virus , Zika virus , Adulto , Masculino , Feminino , Humanos , Infecção por Zika virus/complicações , Infecção por Zika virus/diagnóstico , Febre de Chikungunya/complicações , Febre de Chikungunya/diagnóstico , Febre de Chikungunya/epidemiologia , Dengue/complicações , Dengue/diagnóstico , Dengue/epidemiologia , Coinfecção/epidemiologia , Perda Auditiva/etiologia , Perda Auditiva Neurossensorial/etiologia , AudiçãoRESUMO
ABSTRACT Background: Chikungunya fever is an emerging global infection transmitted by Aedes mosquitoes that manifests as an acute febrile illness with joint pain and can lead to chronic arthritis. The mechanism underlying chronic joint damage remains unclear; however, chronic chikungunya arthritis shares similarities with rheumatoid arthritis. Disease-modifying antirheumatic drugs have revolutionized rheumatoid arthritis treatment by preventing joint damage. However, the role of these therapies in chronic chikungunya arthritis has not been determined. We conducted a systematic review to evaluate the burden of joint structural damage in chronic chikungunya arthritis to help to define the role of disease-modifying therapy in this disease. Methods: This systematic review included retrospective and prospective studies, trials, and case reports evaluating joint damage caused by chikungunya virus. Various databases were searched without any date or language restrictions. Study selection was conducted independently by two researchers, and data were extracted from the articles selected. Results: A total of 108 studies were initially evaluated, with 8 meeting the inclusion criteria. Longitudinal studies have reported persistent joint pain from chikungunya infection and the progression of radiographic joint damage up to 13 years post-infection. Joint imaging revealed synovial inflammation, bone erosion, and cartilage destruction in patients with chronic chikungunya arthritis. Conclusions: Few studies have addressed chikungunya-induced joint damage, limiting our understanding of chronic chikungunya arthritis. Nevertheless, chronic chikungunya arthritis has similarities to rheumatoid arthritis. The success of early disease-modifying antirheumatic drug therapy in rheumatoid arthritis underscores the need for comprehensive research on its role in chikungunya arthritis.
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ABSTRACT Objective: To estimate the cost of illness of Chikungunya in the municipality of Rio de Janeiro, Brazil, in 2019. Methods: The study is a partial economic evaluation carried out with secondary data with free and unrestricted access. Direct outpatient and indirect costs of the acute, post-acute, and chronic phases of Chikungunya fever were estimated, in addition to hospital costs. The estimate of direct costs was performed using the notified cases and the standard treatment flowchart in the state of Rio de Janeiro. The indirect ones consist of loss of productivity and disability, using the burden of disease indicator (Disability-adjusted life year - DALY). Results: The total number of reported cases was 38,830. Total costs were calculated at BRL 279,807,318, with 97% related to indirect costs. Conclusion: The chronic phase and indirect costs were the most expensive. The inability and permanence of Chikungunya differentiate the disease and increase the costs of its treatment.
RESUMO Objetivo: Estimar o custo-doença da chikungunya no município do Rio de Janeiro no ano de 2019. Métodos: O estudo é uma avaliação econômica parcial realizada com dados secundários de acesso livre e irrestrito. Foram estimados os custos diretos ambulatoriais e indiretos das fases aguda, pós-aguda e crônica da febre chikungunya, além dos custos hospitalares. A estimativa dos custos diretos foi realizada através dos casos notificados e do fluxograma padrão de tratamento do estado do Rio de Janeiro. Os indiretos consistem na perda de produtividade e da incapacidade, utilizando o indicador de carga de doença (DALY). Resultados: O número total de casos notificados foi de 38.830. Os custos totais foram calculados em R$ 279.807.318, sendo 97% relacionados aos custos indiretos. Conclusão: A fase crônica e os custos indiretos foram os mais onerosos. A incapacidade e a permanência da chikungunya diferenciam a doença e aumentam os custos de seu tratamento.
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Abstract Background Chikungunya is a mosquito-borne disease caused by the chikungunya virus (CHIKV) and can lead to neurological complications in severe cases. Objective This study examined neuroimaging patterns in chikungunya cases during two outbreaks in Brazil to identify specific patterns for diagnosis and treatment of neuro-chikungunya. Methods Eight patients with confirmed chikungunya and neurological involvement were included. Clinical examinations and MRI scans were performed, and findings were analyzed by neuroradiologists. Data on age, sex, neurological symptoms, diagnostic tests, MRI findings, and clinical outcomes were recorded. Results Patients showed different neuroimaging patterns. Six patients exhibited a "clock dial pattern" with hyperintense dotted lesions in the spinal cord periphery. One patient had thickening and enhancement of anterior nerve roots. Brain MRI revealed multiple hyperintense lesions in the white matter, particularly in the medulla oblongata, in six patients. One patient had a normal brain MRI. Conclusion The "clock dial pattern" observed in spinal cord MRI may be indicative of chikungunya-related nervous system lesions. Isolated involvement of spinal cord white matter in chikungunya can help differentiate it from other viral infections. Additionally, distinct brainstem involvement in chikungunya-associated encephalitis, particularly in the rostral region, sets it apart from other arboviral infections. Recognizing these neuroimaging patterns can contribute to early diagnosis and appropriate management of neuro-chikungunya.
Resumo Antecedentes A chikungunya é uma doença transmitida por mosquitos causada pelo vírus chikungunya (CHIKV) e pode levar a complicações neurológicas em casos graves. Objetivo Este estudo examinou padrões de neuroimagem em casos de chikungunya durante dois surtos no Brasil para identificar padrões específicos para o diagnóstico e tratamento de neurochikungunya. Métodos Oito pacientes com chikungunya confirmada e envolvimento neurológico foram incluídos. Exames clínicos e ressonâncias magnéticas (RM) foram realizados, e os achados foram analisados por neurorradiologistas. Dados sobre idade, sexo, sintomas neurológicos, testes diagnósticos, achados de RM e desfechos clínicos foram registrados. Resultados Os pacientes apresentaram diferentes padrões de neuroimagem. Seis pacientes apresentaram um "padrão de mostrador de relógio" com lesões pontilhadas hiperintensas na periferia da medula espinhal. Um paciente apresentou espessamento e realce das raízes nervosas anteriores. A RM do cérebro revelou múltiplas lesões hiperintensas na substância branca, especialmente no bulbo em seis pacientes. Um paciente apresentou uma RM cerebral normal. Conclusão O "padrão de mostrador de relógio" observado na RM da medula espinhal pode ser indicativo de lesões do sistema nervoso relacionadas à chikungunya. O envolvimento isolado da substância branca da medula espinhal na chikungunya pode ajudar a diferenciá-la de outras infecções virais. Além disso, o envolvimento distinto do tronco cerebral na encefalite associada à chikungunya, especialmente na região rostral, a distingue de outras infecções por arbovírus. O reconhecimento desses padrões de neuroimagem pode contribuir para o diagnóstico precoce e manejo adequado da neurochikungunya.