RESUMO
Background and objectives: Dengue is one of the most common epidemic infections around the world. Dengue infections in older adults are related to an atypical presentation and a high mortality. Frailty is associated with poor recovery from hospitalization due to infection. However, few studies describe frailty and functional decline after dengue infection. The current case series study aims to investigate the baseline frailty status, functional decline, and time to recovery in older adults after dengue infection. Method: We studied seven patients with post-dengue frailty who had been admitted to the geriatric ward in one tertiary medical center in Taiwan during the 2023 dengue fever outbreak. Result: The mean age was 82 years old. The clinical frailty scale worsened from a mean of 4.7 at baseline to 6.3 at dengue diagnosis. The mean Katz Index of independence in activities of daily living decreased from 10.6 at baseline to 4.7 with dengue, and it recovered to 6.7 one month after discharge. Conclusions: Our preliminary data suggest that there is indeed an increase in frailty in older adults due to dengue. Post-dengue frailty and functional decline might be profound and persistent. Acute geriatric care intervention rehabilitation for frailty after dengue may benefit this population.
Assuntos
Dengue , Fragilidade , Humanos , Dengue/complicações , Dengue/fisiopatologia , Dengue/epidemiologia , Masculino , Feminino , Idoso de 80 Anos ou mais , Taiwan/epidemiologia , Idoso , Fragilidade/epidemiologia , Fragilidade/complicações , Idoso Fragilizado/estatística & dados numéricos , Avaliação Geriátrica/métodos , Atividades CotidianasRESUMO
O Tocantins é um Estado endêmico para dengue devido aos elevados índices pluviométricos e do saneamento básico escasso. Esta pesquisa objetivou investigar o número de internações por dengue no Estado do Tocantins entre 2017 e 2022. O estudo consiste em um delineamento transversal retrospectivo quantitativo, realizado a partir de dados coletados no Tabnet/DataSUS. Os resultados encontrados foram compilados no programa Microsoft Excel®, e por meio de gráficos e tabelas, foram evidenciados 28.355 casos de dengue confirmados, dos quais apenas 1.798 (6%) necessitaram de hospitalizações, com maior incidência em 2019, tendo Palmas como município mais acometido. Conclui-se, portanto, que a dengue segue sendo uma doença prevalente no Estado, de modo a demandar atenção de gestores de saúde com vistas a reduzir os números altos de casos por meio de vigilância epidemiológica ativa como, também, fornecer o melhor cuidado para os pacientes diagnosticados com dengue, quer seja no âmbito ambulatorial quer no hospitalar.
Tocantins is an endemic state for dengue due to high rainfall rates and poor sanitation. This research aimed to investigate the number of dengue hospitalizations in the State of Tocantins between 2017 and 2022. The study consists of a retrospective quantitative cross-sectional design, performed from data collected in Tabnet/DataSUS. The results found were compiled in Microsoft Excel® program, and by means of graphs and tables, 28,355 confirmed dengue cases were evidenced, of which only 1,798 (6%) required hospitalizations, with a higher incidence in 2019, with Palmas as the most affected municipality. It is concluded, therefore, that dengue remains a prevalent disease in the state, so as to demand attention from health managers with a view to reducing the high numbers of cases through active epidemiological surveillance as well as providing the best care for patients diagnosed with dengue, whether in the outpatient or hospital setting.
Tocantins es un estado endémico para el dengue debido a las altas tasas de precipitación y al saneamiento deficiente. Esta investigación tuvo como objetivo investigar el número de hospitalizaciones por dengue en el Estado de Tocantins entre 2017 y 2022. El estudio consiste en un diseño cuantitativo transversal retrospectivo, realizado a partir de datos recogidos en Tabnet/DataSUS. Los resultados encontrados fueron compilados en el programa Microsoft Excel®, y por medio de gráficos y tablas, se evidenciaron 28.355 casos confirmados de dengue, de los cuales sólo 1.798 (6%) requirieron hospitalizaciones, con mayor incidencia en 2019, siendo Palmas el municipio más afectado. Se concluye, por lo tanto, que el dengue continúa siendo una enfermedad prevalente en el estado, por lo que demanda la atención de los gestores de salud con miras a reducir las altas cifras de casos a través de la vigilancia epidemiológica activa, así como brindar la mejor atención a los pacientes diagnosticados con dengue, ya sea en el ámbito ambulatorio u hospitalario.
Assuntos
Pré-Escolar , Criança , Adolescente , Adulto , Pessoa de Meia-Idade , Idoso , Prevalência , Dengue/fisiopatologia , Dengue/prevenção & controleRESUMO
Dengue virus (DENV) is a mosquito-borne flavivirus responsible for dengue disease, a major human health concern for which no effective treatment is available. DENV relies heavily on the host cellular machinery for productive infection. Here, we show that the scaffold protein RACK1, which is part of the DENV replication complex, mediates infection by binding to the 40S ribosomal subunit. Mass spectrometry analysis of RACK1 partners coupled to an RNA interference screen-identified Vigilin and SERBP1 as DENV host-dependency factors. Both are RNA-binding proteins that interact with the DENV genome. Genetic ablation of Vigilin or SERBP1 rendered cells poorly susceptible to DENV, as well as related flaviviruses, by hampering the translation and replication steps. Finally, we established that a Vigilin or SERBP1 mutant lacking RACK1 binding but still interacting with the viral RNA is unable to mediate DENV infection. We propose that RACK1 recruits Vigilin and SERBP1, linking the DENV genome to the translation machinery for efficient infection. IMPORTANCE We recently identified the scaffolding RACK1 protein as an important host-dependency factor for dengue virus (DENV), a positive-stranded RNA virus responsible for the most prevalent mosquito-borne viral disease worldwide. Here, we have performed the first RACK1 interactome in human cells and identified Vigilin and SERBP1 as DENV host-dependency factors. Both are RNA-binding proteins that interact with the DENV RNA to regulate viral replication. Importantly, Vigilin and SERBP1 interact with RACK1 and the DENV viral RNA (vRNA) to mediate viral replication. Overall, our results suggest that RACK1 acts as a binding platform at the surface of the 40S ribosomal subunit to recruit Vigilin and SERBP1, which may therefore function as linkers between the viral RNA and the translation machinery to facilitate infection.
Assuntos
Vírus da Dengue , Dengue , Proteínas de Ligação a RNA , Animais , Dengue/fisiopatologia , Vírus da Dengue/fisiologia , Interações entre Hospedeiro e Microrganismos/fisiologia , Humanos , Proteínas de Neoplasias/metabolismo , RNA Viral/genética , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Receptores de Quinase C Ativada/metabolismo , Replicação ViralRESUMO
Las infecciones por arbovirus constituyen un reto significativo para los sistemas de salud. Cada vez se incrementa el reconocimiento de complicaciones del sistema nervioso central secundarias a ellas, lo que puede ser un dilema para su diagnóstico y tratamiento. Los arbovirus pueden alterar los mecanismos de inmunidad innatos del ojo al dañar las barreras óculo-hemáticas. En esta revisión nos propusimos caracterizar los principales hallazgos oftalmológicos de las enfermedades transmitidas por mosquito, como el dengue, el zika y el chikungunya, y su posible fisiopatología. Se realizó una búsqueda de la literatura sobre el tema en la base de datos de PubMED. En los pacientes con zika y chikungunya se reconocieron frecuentemente la conjuntivitis no purulenta y la queratitis. En los casos de dengue el edema macular y las hemorragias retinianas maculares fueron frecuentes; causaron disminución de la visión y defectos campimétricos; la vasculitis y coriorretinitis periférica podía ser asintomática si la mácula no estaba comprometida. Estuvieron implicados la trombocitopenia y otros procesos fisiopatológicos. En las enfermedades estudiadas se reportaron casos raros con parálisis de nervios oculomotores o neuritis óptica como respuesta autoinmune tardía. Recientemente se reportó el síndrome de zika congénito que incluyó múltiples anomalías del desarrollo. En los neonatos afectados se describió la atrofia macular, así como la pigmentación macular bilateral, la hipoplasia del nervio óptico, la catarata, entre otros. Existen diversas lesiones oculares secundarias a infecciones por dengue, zika y chikungunya que merecen reconocimiento, pues deterioran la función visual temporal o permanentemente(AU)
Arbovirus infections pose a significant challenge to health systems. Awareness of the secondary central nervous system complications caused by these infections is on the increase, which may be a dilemma for their diagnosis and treatment. Arboviruses may alter the innate immunity mechanisms of the eye by damaging blood-retinal barriers. The objective of this review was to characterize the main ophthalmological findings of mosquito-borne diseases, such as dengue, zika and chikungunya, and their possible physiopathology. A bibliographic search about the topic was conducted in the database PubMed. Non-purulent conjunctivitis and keratitis were frequently found in zika and chikungunya patients. Dengue cases often presented macular edema and macular retinal hemorrhage, which caused vision reduction, as well as campimetric defects. Vasculitis and peripheral chorioretinitis could be asymptomatic if the macula was not involved. Thrombocytopenia and other physiopathological processes were also present. Oculomotor nerve palsy and optic neuritis as a late autoimmune response were rarely reported in the diseases studied. Recent reports refer to congenital zika syndrome, which causes multiple developmental abnormalities. Macular atrophy, bilateral macular pigmentation, optic nerve hypoplasia and cataract, among other disorders, were described in affected neonates. A variety of ocular lesions secondary to dengue, zika and chikungunya infection deserve recognition, for they damage visual function either temporarily or permanently(AU)
Assuntos
Humanos , Infecções por Arbovirus/etiologia , Doenças do Nervo Oculomotor , Dengue/fisiopatologia , Febre de Chikungunya/fisiopatologia , Infecção por Zika virus/fisiopatologia , Trombocitopenia , Literatura de Revisão como Assunto , Sistema Nervoso Central , Traumatismos OcularesRESUMO
A dysregulated or exacerbated inflammatory response is thought to be the key driver of the pathogenesis of severe disease caused by the mosquito-borne dengue virus (DENV). Compounds that restrict virus replication and modulate the inflammatory response could thus serve as promising therapeutics mitigating the disease pathogenesis. We and others have previously shown that macrophages, which are important cellular targets for DENV replication, differentiated in the presence of bioactive vitamin D (VitD3) are less permissive to viral replication, and produce lower levels of pro-inflammatory cytokines. Therefore, we here evaluated the extent and kinetics of innate immune responses of DENV-2 infected monocytes differentiated into macrophages in the presence (D3-MDMs) or absence of VitD3 (MDMs). We found that D3-MDMs expressed lower levels of RIG I, Toll-like receptor (TLR)3, and TLR7, as well as higher levels of SOCS-1 in response to DENV-2 infection. D3-MDMs produced lower levels of reactive oxygen species, related to a lower expression of TLR9. Moreover, although VitD3 treatment did not modulate either the expression of IFN-α or IFN-ß, higher expression of protein kinase R (PKR) and 2'-5'-oligoadenylate synthetase 1 (OAS1) mRNA were found in D3-MDMs. Importantly, the observed effects were independent of reduced infection, highlighting the intrinsic differences between D3-MDMs and MDMs. Taken together, our results suggest that differentiation of MDMs in the presence of VitD3 modulates innate immunity in responses to DENV-2 infection.
Assuntos
Diferenciação Celular , Vírus da Dengue/fisiologia , Dengue/imunologia , Macrófagos/citologia , Vitamina D/imunologia , 2',5'-Oligoadenilato Sintetase/genética , 2',5'-Oligoadenilato Sintetase/imunologia , Adulto , Animais , Dengue/genética , Dengue/fisiopatologia , Dengue/virologia , Vírus da Dengue/classificação , Vírus da Dengue/genética , Feminino , Humanos , Imunidade Inata , Interferon beta/genética , Interferon beta/imunologia , Macrófagos/imunologia , Masculino , Monócitos/citologia , Monócitos/imunologia , Replicação Viral , Adulto JovemAssuntos
Valvuloplastia com Balão/métodos , Dengue , Ecocardiografia/métodos , Estenose da Valva Mitral , Derrame Pleural , Radiografia Torácica/métodos , Insuficiência Respiratória , Ultrassonografia/métodos , Adulto , Cuidados Críticos/métodos , Dengue/sangue , Dengue/complicações , Dengue/diagnóstico , Dengue/fisiopatologia , Humanos , Masculino , Estenose da Valva Mitral/complicações , Estenose da Valva Mitral/diagnóstico por imagem , Estenose da Valva Mitral/fisiopatologia , Estenose da Valva Mitral/cirurgia , Derrame Pleural/diagnóstico por imagem , Derrame Pleural/etiologia , Edema Pulmonar/etiologia , Edema Pulmonar/fisiopatologia , Respiração Artificial/métodos , Insuficiência Respiratória/diagnóstico , Insuficiência Respiratória/etiologia , Insuficiência Respiratória/fisiopatologia , Insuficiência Respiratória/terapia , Resultado do TratamentoRESUMO
Although antiviral antibodies generally confer protective functions, antibodies against dengue virus (DENV) are associated with enhanced disease susceptibility. Antibodies can mediate DENV infection of leukocytes via Fcγ receptors, likely contributing to dengue disease pathogenesis. To determine if this mechanism accounts for variable disease severity, we examined Fab and Fc structures of anti-DENV antibodies from patients before and after infection and with variable disease outcomes. Neither antibody titers nor neutralizing activity correlated with disease severity in DENV-infected populations. Rather, DENV infection induced a specific increase in immunoglobulin G1 (IgG1) afucosylation, and the levels of afucosylated IgG1 were predictive of dengue disease severity. Thus, the IgG1 fucosylation status represents a robust prognostic tool for dengue disease, highlighting the key role of the Fc glycan structure in dengue pathogenesis.
Assuntos
Anticorpos Antivirais/sangue , Anticorpos Antivirais/química , Vírus da Dengue/imunologia , Dengue/imunologia , Fucose/análise , Dengue Grave/imunologia , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/química , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Anticorpos Facilitadores , Criança , Coinfecção/imunologia , Dengue/fisiopatologia , Feminino , Humanos , Fragmentos Fc das Imunoglobulinas/química , Fragmentos Fc das Imunoglobulinas/imunologia , Imunoglobulina G/sangue , Imunoglobulina G/química , Imunoglobulina G/imunologia , Masculino , Receptores de IgG/química , Receptores de IgG/imunologia , Dengue Grave/fisiopatologia , Índice de Gravidade de Doença , Infecção por Zika virus/imunologiaRESUMO
Dengue viral infections present with a wide clinical spectrum ranging from asymptomatic to severe manifestations with organ involvement. The term "expanded dengue syndrome" has been commonly used to illustrate the unusual or atypical manifestations; acute kidney injury (AKI) is one of the atypical manifestations of this syndrome. The use of heterogeneous criteria to determine the presence of AKI in dengue patients due to the vast diversity in populations led to difficulties in assessing the true incidence of dengue-associated AKI. This review presents a variable, but often high, frequency of dengue-associated AKI among vastly diverse populations with various disease severities. Dengue-associated AKI is not an uncommon complication, and its importance has often been neglected during the management of dengue patients. The risk factors and certain clinical and laboratory findings commonly reported among dengue patients with AKI should be considered to support a timely diagnosis and case management. This review highlights the need for clinicians to be aware of dengue-associated AKI to reduce the morbidity and mortality associated with this common and important tropical disease.
Assuntos
Injúria Renal Aguda/etiologia , Injúria Renal Aguda/fisiopatologia , Dengue/complicações , Dengue/fisiopatologia , Monitoramento Epidemiológico , Injúria Renal Aguda/epidemiologia , Dengue/epidemiologia , Previsões , Humanos , Incidência , Fatores de RiscoRESUMO
BACKGROUND: As coronavirus 2019 (COVID-19) is spreading globally, several countries are handling dengue epidemics. As both infections are deemed to share similarities at presentation, it would be useful to distinguish COVID-19 from dengue in the context of co-epidemics. Hence, we performed a retrospective cohort study to identify predictors of both infections. METHODOLOGY/PRINCIPAL FINDINGS: All the subjects suspected of COVID-19 between March 23 and May 10, 2020, were screened for COVID-19 within the testing center of the University hospital of Saint-Pierre, Reunion island. The screening consisted in a questionnaire surveyed in face-to-face, a nasopharyngeal swab specimen for the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) reverse transcription polymerase chain-reaction and a rapid diagnostic orientation test for dengue. Factors independently associated with COVID-19 or with dengue were sought using multinomial logistic regression models, taking other febrile illnesses (OFIs) as controls. Adjusted Odds ratios (OR) and 95% Confidence Intervals (95%CI) were assessed. Over a two-month study period, we diagnosed 80 COVID-19, 61 non-severe dengue and 872 OFIs cases eligible to multivariate analysis. Among these, we identified delayed presentation (>3 days) since symptom onset (Odds ratio 1.91, 95% confidence interval 1.07-3.39), contact with a COVID-19 positive case (OR 3.81, 95%CI 2.21-6.55) and anosmia (OR 7.80, 95%CI 4.20-14.49) as independent predictors of COVID-19, body ache (OR 6.17, 95%CI 2.69-14.14), headache (OR 5.03, 95%CI 1.88-13.44) and retro-orbital pain (OR 5.55, 95%CI 2.51-12.28) as independent predictors of dengue, while smoking was less likely observed with COVID-19 (OR 0.27, 95%CI 0.09-0.79) and upper respiratory tract infection symptoms were associated with OFIs. CONCLUSIONS/SIGNIFICANCE: Although prone to potential biases, these data suggest that non-severe dengue may be more symptomatic than COVID-19 in a co-epidemic setting with higher dengue attack rates. At clinical presentation, nine basic clinical and epidemiological indicators may help to distinguish COVID-19 or dengue from each other and other febrile illnesses.
Assuntos
COVID-19/diagnóstico , Dengue/diagnóstico , SARS-CoV-2/isolamento & purificação , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19/epidemiologia , COVID-19/fisiopatologia , Teste para COVID-19 , Criança , Pré-Escolar , Estudos de Coortes , Dengue/epidemiologia , Dengue/fisiopatologia , Diagnóstico Diferencial , Reações Falso-Negativas , Reações Falso-Positivas , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Reunião/epidemiologia , Adulto JovemRESUMO
Galectin-9 (Gal-9) is a ß-galactoside-binding lectin capable of promoting or suppressing the progression of infectious diseases. This protein is susceptible to cleavage of its linker-peptides by several proteases, and the resulting cleaved forms, N-terminal carbohydrate recognition domain (CRD) and C-terminal CRD, bind to various glycans. It has been suggested that full-length (FL)-Gal-9 and the truncated (Tr)-Gal-9s could exert different functions from one another via their different glycan-binding activities. We propose that FL-Gal-9 regulates the pathogenesis of infectious diseases, including human immunodeficiency virus (HIV) infection, HIV co-infected with opportunistic infection (HIV/OI), dengue, malaria, leptospirosis, and tuberculosis (TB). We also suggest that the blood levels of FL-Gal-9 reflect the severity of dengue, malaria, and HIV/OI, and those of Tr-Gal-9 markedly reflect the severity of HIV/OI. Recently, matrix metallopeptidase-9 (MMP-9) was suggested to be an indicator of respiratory failure from coronavirus disease 2019 (COVID-19) as well as useful for differentiating pulmonary from extrapulmonary TB. The protease cleavage of FL-Gal-9 may lead to uncontrolled hyper-immune activation, including a cytokine storm. In summary, Gal-9 has potential to reflect the disease severity for the acute and chronic infectious diseases.
Assuntos
Doenças Transmissíveis/sangue , Galectinas/sangue , Doença Aguda , Sequência de Aminoácidos , COVID-19/sangue , COVID-19/fisiopatologia , Doença Crônica , Doenças Transmissíveis/imunologia , Doenças Transmissíveis/fisiopatologia , Dengue/sangue , Dengue/fisiopatologia , Galectinas/genética , Galectinas/metabolismo , Infecções por HIV/sangue , Infecções por HIV/fisiopatologia , Humanos , Fatores Imunológicos/metabolismo , Leptospirose/sangue , Leptospirose/fisiopatologia , Malária/sangue , Malária/fisiopatologia , Tuberculose/sangue , Tuberculose/fisiopatologiaRESUMO
BACKGROUND: The pandemic of this century has overwhelmed the healthcare systems of affected countries, and all resources have been diverted to coronavirus disease 2019. At the onset, coronavirus disease 2019 can present as any other acute febrile undifferentiated illness. In tropical regions, clinicians are increasingly challenged to differentiate these febrile illnesses without the use of diagnostics. With this pandemic, many of these tropical diseases are neglected and go underreported. Dengue is holoendemic in the Maldives, and dengue viruses circulate throughout the year. Reports about coinfections with dengue virus and severe acute respiratory syndrome coronavirus 2 are scarce, and the outcome and the dynamics of the disease may be altered in the presence of coinfection. We have described the clinical manifestation and serial laboratory profile, and highlighted the atypical findings uncommon in dengue infection. CASE PRESENTATION: Case 1 was a 39-year old Asian male, presented on day 6 of dengue infection with warning signs. Reverse transcription polymerase chain reaction for severe acute respiratory syndrome coronavirus 2 that was done as per hospital protocol was found to be positive. Case 2 was a 38-year old Asian male, was admitted on day 5 of illness with symptoms of acute respiratory infection with positive reverse transcription polymerase chain reaction for severe acute respiratory syndrome coronavirus 2. Evaluation of progressive leukopenia and thrombocytopenia showed positive dengue serology. CONCLUSION: Clinicians must be conscientious when working on the differential diagnosis of possible tropical diseases in cases of coronavirus disease 2019, specifically, when patients develop hemoconcentration, thrombocytopenia, and transaminitis with elevated expression of aspartate higher than alanine transaminase, which is frequently observed in dengue infection. Caution must be taken during the administration of intravenous fluids when treating patients with coronavirus disease 2019 and dengue coinfection, as coronavirus disease 2019 patients are more prone to develop pulmonary edema. Timely diagnosis and appropriate management are essential to avoid the devastating complications of severe forms of dengue infection. It is important to repeat and reconfirm the dengue serology in coronavirus disease 2019 patients to avoid false positivity. Diligence and care must be taken not to neglect other endemic tropical diseases in the region during the present pandemic.
Assuntos
COVID-19/complicações , Dengue/complicações , Leucopenia/sangue , Trombocitopenia/sangue , Dor Abdominal/fisiopatologia , Adulto , Anosmia/fisiopatologia , COVID-19/sangue , COVID-19/fisiopatologia , Teste de Ácido Nucleico para COVID-19 , Coinfecção , Tosse/fisiopatologia , Dengue/sangue , Dengue/fisiopatologia , Dengue/terapia , Diarreia/fisiopatologia , Disgeusia/fisiopatologia , Febre/fisiopatologia , Hidratação , Cefaleia/fisiopatologia , Humanos , Masculino , Mialgia/fisiopatologia , Faringite/fisiopatologia , SARS-CoV-2 , Vômito/fisiopatologiaRESUMO
Dengue virus (DENV) is a mosquito-borne RNA virus, which infects nearly 3.97 billion people every year in the tropical and subtropical regions of the world. DENV infections can range from unrecognizable illnesses to a spectrum of clinical manifestations such as dengue fever (DF), and more severe and potentially lethal dengue hemorrhagic fever (DHF). The variability of clinical manifestations induced by DENV can be attributed to a variety of extrinsic and intrinsic factors including virulence of the DENV strains and host genetic factors influencing the immune response. Interferon gamma (IFN-Y) is one of the critical immunomodulators implicated in DENV infection, and recent case-control association studies examined the role of +874 T/A polymorphism (rs2430561) of the IFN-Y gene in dengue clinical outcomes. Since the results of the association studies on DENV infection and IFN-Y +874 T/A polymorphism were inconsistent, we performed a meta-analysis to derive a more precise estimate of the association. Searching the databases until 15 March 2020, we identified five studies with a total of 1412 subjects (582 cases and 830 controls), which were included in this meta-analysis. The pooled odds ratio (ORs) with corresponding 95% confidence intervals (CIs) were calculated to evaluate the strength of the association. Pooled data indicated significant association of the TT genotype with DENV infection (DI), DF, and DHF in the recessive model TT vs AT+AA: OR (DI) = 1.47, 95% CI (1.10-1.97), P = 0.01; OR (DF) = 1.40, 95% CI (1.00-1.94), P = 0.04, OR (DHF) = 1.73, 95% CI (1.05-2.86), P = 0.03, and the genotype contrast TT vs AT: OR (DI) = 1.70, 95% CI (1.18-2.47); P = 0.005, OR (DF) = 1.72, 95% CI (1.12-2.66), P = 0.014, OR (DHF) = 1.76, 95% CI (1.01-3.06), P = 0.046. The genotype contrast AA vs AT showed significant association with the milder form of dengue (DF), OR (DF) = 1.60, 95% CI (1.07-2.41), P = 0.023, but not with the severe form (DHF). Taken together, this meta-analysis indicated that both the homozygous genotypes conferred risk to dengue, albeit with varied clinical outcomes, and revealed a protective role of the heterozygous genotype against DENV infection.
Assuntos
Dengue/genética , Interferon gama/genética , Polimorfismo de Nucleotídeo Único , Estudos de Casos e Controles , Dengue/imunologia , Dengue/fisiopatologia , Humanos , Interferon gama/imunologiaRESUMO
In mouse models of dengue virus (DENV) infection, 18F-FDG PET is able to sensitively detect tissue-specific sites of inflammation and disease activity, as well as track therapeutic response to anti- DENV agents. However, the use of 18F-FDG PET to study the pathogenesis of inflammation and disease activity in DENV infection in humans, has not been clinically validated. Here we report the 18F-FDG PET imaging results of two patients during the febrile phase of acute DENV infection, paired with serial serum viral load, NS1 and proinflammatory cytokine measurements. Our findings demonstrate that 18F-FDG PET is able to sensitively detect and quantify organ-specific inflammation in the lymph nodes and spleen, in classic acute dengue fever. This raises the potential for 18F-FDG PET to be used as a research tool that may provide further insights into disease pathogenesis.
Assuntos
Dengue/sangue , Dengue/fisiopatologia , Fluordesoxiglucose F18/metabolismo , Inflamação/fisiopatologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Tomografia por Emissão de Pósitrons/métodos , Doença Aguda , Adulto , Convalescença , Citocinas/análise , Dengue/virologia , Feminino , Humanos , Inflamação/imunologia , Linfonodos/patologia , Masculino , Pessoa de Meia-Idade , Baço/patologia , Carga ViralRESUMO
BACKGROUND: In this mini review, we discuss some of the atypical neurological manifestations of dengue virus and attempt to bring them to attention to highlight the neurotropic property of the dengue virus. METHODS: Cases were chosen from retrospective hospital and outpatient records of all patients seropositive for dengue who attended the neurology referral. Seven patients have been chosen as illustrative examples of dengue-associated neurological involvement. We discuss the various central and peripheral nervous system involvement of patients and discuss the relevant findings in them. CONCLUSION: Through this case series, we wish to highlight that the dengue virus can affect the nervous system at various targets, using multiple mechanisms of pathogenesis to generate a plethora of presentations. Hence, it is vital to be aware of its presentations to be able to diagnose dengue and treat it accordingly.
Assuntos
Vírus da Dengue/patogenicidade , Dengue , Doenças do Sistema Nervoso , Dengue/diagnóstico , Dengue/fisiopatologia , Diagnóstico Diferencial , Humanos , Doenças do Sistema Nervoso/diagnóstico , Doenças do Sistema Nervoso/virologia , Exame Neurológico/métodosRESUMO
BACKGROUND: Dengue virus (DENV) is estimated to infect 390 million people annually. However, few host factors that alter disease severity are known. Malnutrition, defined as both over- and undernutrition, is a growing problem worldwide and has long been linked to dengue disease severity by epidemiological and anecdotal observations. Accordingly, we sought to establish a mouse model to assess the impact of nutritional status on DENV disease severity. RESULTS: Using transiently immunocompromised mice, we established a model of mild dengue disease with measurable viremia. We then applied it to study the effects of healthy weight, obese, and low-protein diets representing normal, over-, and undernutrition, respectively. Upon infection with DENV serotype 2, obese mice experienced more severe morbidity in the form of weight loss and thrombocytopenia compared to healthy weight groups. Additionally, obesity altered cytokine expression following DENV infection. Although low protein-fed mice did not lose significant weight after DENV2 infection, they also experienced a reduction in platelets as well as increased spleen pathology and viral titers. CONCLUSIONS: Our results indicate that obese or undernourished mice incur greater disease severity after DENV infection. These studies establish a role for nutritional status in DENV disease severity.
Assuntos
Peso Corporal/fisiologia , Dengue/virologia , Dieta Hiperlipídica/efeitos adversos , Dieta com Restrição de Proteínas/efeitos adversos , Estado Nutricional , Animais , Dengue/fisiopatologia , Modelos Animais de Doenças , Feminino , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Viremia/fisiopatologiaRESUMO
Dengue virus (DENV) infection is one of the most widespread mosquito-borne viral infections. Liver injury is commonly observed in severe DENV infection, and the present study aimed to examine the efficacy of crocetin treatment in an immunocompetent mouse model of DENV infection exhibiting liver injury. The efficacy of crocetin treatment in DENV-induced liver injury was assessed via both transaminase levels and histopathology analysis. A real-time polymerase chain reaction array was then used to describe the expression of 84 apoptosis-related genes. Using real-time RT-PCR and Western blot analysis, the gene expressions of host factors were investigated. Additionally, the effect of crocetin in NF-kB signaling during DENV infection was studied. We did not observe any significant reduction in virus production when DENV-infected mice were treated with crocetin. However, DENV-infected mice treated with crocetin showed reduced DENV-induced apoptosis. The real-time polymerase chain reaction array revealed pro-inflammatory cytokine expressions to be significantly reduced in the crocetin-treated DENV-infected mice. We also found that crocetin could effectively modulate antioxidant status in DENV-infected mice. Moreover, crocetin demonstrated the ability to reduce the nuclear translocation of NF-kB in DENV-infected mice. Our results suggest that crocetin treatment does not inhibit DENV replication in the liver of DENV-infected mice; however, we did find that crocetin improves host responses that reduce liver injury.
Assuntos
Carotenoides/uso terapêutico , Vírus da Dengue/patogenicidade , Dengue/tratamento farmacológico , Hepatopatias/tratamento farmacológico , Hepatopatias/virologia , Replicação Viral/efeitos dos fármacos , Vitamina A/análogos & derivados , Transporte Ativo do Núcleo Celular , Animais , Apoptose/genética , Dengue/complicações , Dengue/fisiopatologia , Modelos Animais de Doenças , Expressão Gênica , Fígado/efeitos dos fármacos , Fígado/patologia , Fígado/virologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Transaminases/análise , Vitamina A/uso terapêuticoRESUMO
BACKGROUND: Given the lack of specific antiviral drugs and effective vaccine for dengue infection, factors such as host nutritional status that may alter disease progression require investigation. This study examined the relationship between baseline nutritional status and severity of dengue infection in pediatric patients. METHODS: Data from dengue patients 1-14 years of age treated at four hospitals in southern Thailand (2017-2018) were reviewed. Dengue infection was classified as dengue fever, dengue hemorrhagic fever and dengue shock syndrome. Children's nutritional status was assessed based on international and national growth charts. Binary logistic regression was used to identify factors associated with dengue severity and malnutrition. RESULTS: Overall, 248, 281 and 43 patients had dengue fever, dengue hemorrhagic fever and dengue shock syndrome, respectively. Overweight was associated with increased risk of dengue severity [odds ratio (OR) = 1.76, 95% confidence interval (CI): 1.13-2.75, P = 0.012; OR = 1.84, 95% CI: 1.09-3.09, P = 0.022, per international and national growth criteria, respectively). Stunting was associated with decreased risk of dengue severity (OR = 0.54, 95% CI: 0.33-0.88, P = 0.013; OR = 0.61, 95% CI: 0.39-0.95, P = 0.030, per international and national growth criteria, respectively). Being overweight was significantly and positively associated with levels of hemoglobin >14 g/dL, hematocrit >42%, hemoconcentration ≥20% and platelet count ≤50,000/mm, whereas being stunted was significantly and negatively associated with levels of hemoglobin >14 g/dL and hematocrit >42%. CONCLUSIONS: These findings support a hypothesis that malnutrition might influence the severity of dengue infection through host immune response. Overweight children with dengue infections should be closely observed for early signs of severe dengue infection.
Assuntos
Dengue , Estado Nutricional/fisiologia , Adolescente , Criança , Pré-Escolar , Dengue/epidemiologia , Dengue/fisiopatologia , Feminino , Humanos , Lactente , Masculino , Obesidade Infantil , Estudos Retrospectivos , Fatores de Risco , TailândiaRESUMO
CASE REPORT: A 26-year-old woman with sickle cell disease (SCD) on chronic transfusion therapy complained of severe arthralgia, myalgia, abdominal pain, headache, and fever 24 hours after transfusion of a red blood cells (RBCs). Dengue virus (DENV) infection was suspected and the patient was hospitalized for clinical support and RBC transfusion, to lower the hemoglobin S to less than 30%. The patient's clinical condition improved approximately 8 days after the onset of symptoms. RESULTS: DENV type 2 (DENV-2) TaqMan real-time polymerase chain reaction was negative in the patient's pretransfusion sample while the posttransfusion sample was positive (Ct, 27.8), suggesting a high viral load and an acute infection. To investigate DENV transfusion transmission (TT-DENV) the stored donor serum was tested and was also positive (Ct, 25.8). Molecular typing confirmed the presence of DENV-2. The phylogenetic analysis of the DENV-2 strains obtained from both donor and patient samples were classified as the Southeast Asia-American genotype (Genotype III) and demonstrated 100% genomic identity, indicating TT-DENV. CONCLUSION: This is the first description of TT-DENV in a SCD patient. A presumed high viral load in the transfused RBC unit probably determined the early clinical manifestation. In endemic regions dengue fever should be considered as differential diagnosis in SCD patients with fever and acute pain crisis, mainly during DENV outbreaks.
Assuntos
Anemia Falciforme , Vírus da Dengue , Dengue , Transfusão de Eritrócitos/efeitos adversos , Vasoconstrição , Adulto , Anemia Falciforme/sangue , Anemia Falciforme/fisiopatologia , Anemia Falciforme/terapia , Dengue/sangue , Dengue/etiologia , Dengue/fisiopatologia , Feminino , Humanos , Reação Transfusional/sangue , Reação Transfusional/fisiopatologiaRESUMO
BACKGROUND: Monitoring of blood pressure is an important part of management of dengue illness. Large scale studies of temporal trend of blood pressure in adult dengue are lacking. In this study, we examined the differences in time trend of systolic (SBP) and diastolic blood pressure (DBP) in patients with and without severe dengue (SD), dengue hemorrhagic fever (DHF) and pre-existing hypertension, and elderly versus non-elderly patients. METHODS: We studied a retrospective cohort from 2005 to 2008 of 6,070 hospitalized adult dengue patients confirmed by polymerase chain reaction or clinical criteria plus positive dengue serology. Dengue severity was defined according to World Health Organization 1997 and 2009 guidelines. We used Bayesian hierarchical Markov models to compare the daily mean SBP and DBP between different subgroups. Analysis was conducted by day of defervescence (denoted as day 0), and day of illness onset (denoted as day 1) respectively. RESULTS: SBP decreased to a nadir during the critical phase before defervescence and was significantly lower for patients with SD or DHF, compared with patients without SD or DHF. DBP increased marginally more for patients with SD or DHF in the critical phase before defervescence. By day of defervescence, comparison of patients with and without SD showed significant difference in SBP from day -6 to day +6, except days +1, +3 and +5, and similarly in DBP except days 0, and +4 to +6. Comparison of patients with and without DHF showed significant difference in SBP from day -6 to day -1, but for DBP, significant difference was noted from day -6 to day +6, except day -2 to day 0. By day of illness, SBP differed significantly between patients with and without SD from illness days 1 to 10, and DBP from illness days 7 to 12. Between patients with and without DHF, SBP differed significantly on illness days 1, 2, 4 to 7, while DBP from days 7 to 12. On analysis by days of defervescence or by days of illness, elderly patients and those with hypertension showed consistently higher SBP and DBP throughout their hospitalization, as compared with their younger and non-hypertensive counterparts. CONCLUSION: In SD or DHF, SBP decreased to a nadir around the day of defervescence, and recovered to a level exceeding that in febrile phase by days 2 or 3 post-defervescence. Elderly patients and patients with pre-existing hypertension maintained higher SBP and DBP throughout the duration of dengue infection.
Assuntos
Pressão Sanguínea , Dengue/fisiopatologia , Adulto , Dengue/complicações , Vírus da Dengue/isolamento & purificação , Feminino , Hospitalização , Humanos , Hipertensão/complicações , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
RATIONALE: Acute promyelocytic leukemia (APL) is an uncommon subtype of acute myeloid leukemia (AML). M3v phenotype is a less common presentation of APL and these patients usually present with leukocytosis and abnormal promyelocytes that are characterized by sparse granulation and are less likely to have faggot cells with multiple Auer rods. Distinguishing M3v phenotype from acute febrile illness can be challenging as the diagnosis relies on examination of peripheral smear. PATIENT CONCERNS: Fifty-seven-year-old female who presented after recent trip to Dominican Republic for high grade fever and gum bleeding. She was exposed to patients with Dengue fever during her stay. At presentation, patient had leukocytosis, thrombocytopenia, and urinalysis showing bacteria and white cell. She was started on treatment for urinary tract infection. Patient remained febrile and thrombocytopenia worsened. On day 2, flow cytometry of the peripheral smear showed 43% medium sized blasts. Fluorescence in situ hybridization was positive for promyelocytic leukemia/retinoic acid receptor alpha. DIAGNOSES: The patient was diagnosed with APL. INTERVENTIONS: Patient was started on treatment with all-trans retinoic acid and arsenic trioxide along with supportive care OUTCOMES:: Patient had a favorable clinical response and her symptoms subsided. LESSONS: Flow cytometry of the peripheral smear is key to diagnosis of suspected APL. One must maintain high suspicion for this life-threatening condition as early diagnosis saves lives.