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1.
Microb Pathog ; 173(Pt B): 105870, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36356794

RESUMEN

OBJECTIVES: Dengue viral (DENV) infection is most prevalent arboviral infection in India resulting in wide-range of symptomatic manifestation from simple (DF) to severe dengue (SD). DENV is internalized by dendritic cell receptor, DC-SIGN, which in turn activates inflammatory cytokines: NFκß, IL-10 as adaptive immune response. Present study focused on role of DC-SIGN polymorphisms and these cytokines in SD development among eastern Indian patients. METHOD: DC-SIGN polymorphisms (rs735239, rs4804803, rs2287886) and NFκß, IL-10 concentrations were analysed among 179 dengue patients and 123 healthy individuals by PCR-RFLP and sandwich ELISA, respectively. DENV copies/ml and serotype in patient-sera were measured by quantitative and qualitative real time PCR, respectively. Statistical and haplotype analysis were performed by GraphPad-Prism and SNPStat, respectively. RESULT: Prevalence of DENV serotypes among infected patients: DENV2>DENV4>DENV3>DENV1; those with DENV3 infection reported significantly increased IL-10 level. NFκß and IL-10 concentrations were significantly elevated among SD patients. ROC curve analysis predicted cut-off values of NFκß>13.46 ng/ml and IL-10 > 490.5 pg/ml to detect SD among infected patients with a good sensitivity and specificity. Patients with rs735239-GG, rs2287886-GG genotypes and GGG, GAG haplotypes were significantly associated with SD development, whereas, those with rs4804803-AG exhibited high DENVcopies/ml. Patients with these haplotypes also demonstrated increased NFκß and IL-10. CONCLUSION: This study emphasised importance of DC-SIGN GGG and GAG haplotypes, NFκß and IL-10 concentrations in WHO-defined severe dengue development among infected patients.


Asunto(s)
Virus del Dengue , Dengue , Dengue Grave , Humanos , Anticuerpos Antivirales , Dengue/genética , Virus del Dengue/genética , Haplotipos , Interleucina-10/genética , Índice de Severidad de la Enfermedad , FN-kappa B
2.
Eur J Clin Microbiol Infect Dis ; 39(10): 1925-1932, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32504313

RESUMEN

Chikungunya (CHIKV) reemerged in India after a gap of 32 years, in 2005-2006 and has established endemicity in Pune. To assess the degree of CHIKV exposure, we estimated age-stratified prevalence of IgG antibodies to CHIKV in Pune population. This retrospective study utilized age-stratified serum samples collected from 15 wards of Pune in 2017 for dengue (DENV) virus study. Indirect anti-CHIKV-IgG ELISA was developed and used to test 1904 samples. Exposure to CHIKV and DENV was compared in the same population. CHIKV-specific plaque reduction neutralization test (PRNT) was employed to evaluate ELISA positivity and neutralizing potential of anti-CHIKV-IgG antibodies. Indirect ELISA showed 98.5% concordance with commercial ELISA. Seropositivity to CHIKV was 46.4%, one-third children < 15 years being antibody positive. A significant increase (45%, p = 0.026-0.038) was noted at 16-25 years and varied between 48 and 56% until the age 65. In elderly (65 + years), antibody positivity was reduced (41%, p = 0.01). In children, CHIKV-PRNT50 titers increased with age and remained comparable from the age group 11-15 until > 65. Exposure to DENV was higher than CHIKV. Lower exposure of children and elderly could be due to lesser exposure to the vectors. High prevalence of IgG antibodies needs to be addressed while planning vaccine studies for CHIKV.


Asunto(s)
Fiebre Chikungunya/epidemiología , Virus Chikungunya/inmunología , Adolescente , Adulto , Factores de Edad , Anciano , Fiebre Chikungunya/sangre , Fiebre Chikungunya/virología , Niño , Preescolar , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Inmunoglobulina G/sangre , India/epidemiología , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Prevalencia , Curva ROC , Estudios Retrospectivos , Sensibilidad y Especificidad , Adulto Joven
3.
Front Cell Infect Microbiol ; 14: 1264525, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38585651

RESUMEN

Introduction: Dengue is an arboviral disease causing severe illness in over 500,000 people each year. Currently, there is no way to constrain dengue in the clinic. Host kinase regulators of dengue virus (DENV) infection have the potential to be disrupted by existing therapeutics to prevent infection and/or disease progression. Methods: To evaluate kinase regulation of DENV infection, we performed kinase regression (KiR), a machine learning approach that predicts kinase regulators of infection using existing drug-target information and a small drug screen. We infected hepatocytes with DENV in vitro in the presence of a panel of 38 kinase inhibitors then quantified the effect of each inhibitor on infection rate. We employed elastic net regularization on these data to obtain predictions of which of 291 kinases are regulating DENV infection. Results: Thirty-six kinases were predicted to have a functional role. Intriguingly, seven of the predicted kinases - EPH receptor A4 (EPHA4), EPH receptor B3 (EPHB3), EPH receptor B4 (EPHB4), erb-b2 receptor tyrosine kinase 2 (ERBB2), fibroblast growth factor receptor 2 (FGFR2), Insulin like growth factor 1 receptor (IGF1R), and ret proto-oncogene (RET) - belong to the receptor tyrosine kinase (RTK) family, which are already therapeutic targets in the clinic. We demonstrate that predicted RTKs are expressed at higher levels in DENV infected cells. Knockdown of EPHB4, ERBB2, FGFR2, or IGF1R reduces DENV infection in hepatocytes. Finally, we observe differential temporal induction of ERBB2 and IGF1R following DENV infection, highlighting their unique roles in regulating DENV. Discussion: Collectively, our findings underscore the significance of multiple RTKs in DENV infection and advocate further exploration of RTK-oriented interventions against dengue.


Asunto(s)
Virus del Dengue , Dengue , Humanos , Virus del Dengue/fisiología , Receptor EphA1 , Hepatocitos/metabolismo , Tirosina , Replicación Viral
4.
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.

5.
Front Public Health ; 10: 1074028, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36600940

RESUMEN

Introduction: The Aedes mosquito species, which are the vectors for the transmission of the dengue virus (DENV) to humans, are becoming increasingly susceptible to the formidable effects of influential factors, especially temperature. However, there are still very few studies that have systematically reviewed the existing literature. Hence, in the present study, a systematic literature review and meta-analysis was conducted into the effects of temperature on dengue vectors. Method: Several research methodologies were incorporated into the current study, and a review was carried out using PRISMA as a guide. The publications for this study were chosen from two prominent databases, Scopus and Web of Science. All of the studies were assessed, reviewed, and evaluated independently by two reviewers. The meta-analysis tool, Review Manager (RevMan Copenhagen Version 5.4.1), was used to record the extracted data for the meta-analysis. Moran's I 2 and a funnel plot were utilized to measure heterogeneity, and publication bias was investigated. A 95% confidence interval (CI) and overall risk difference (RD) were estimated using a random-effects model. Result and discussion: As a consequence of the search efforts, a total of 46 articles were selected for inclusion in the systematic review and meta-analysis. This review was divided into five major themes, based on a thematic analysis: (i) hatching rate, (ii) development time, (iii) longevity, (iv) survival rate, and (v) wing morphology. In addition, the development time, survival rate, and wing morphology revealed significantly higher risk differences between the maximum and minimum temperatures (RD: 0.26, 95% CI: 0.16, 0.36; p = < 0.00001; RD: 0.10, 95% CI: 0.05, 0.14; p < 0.0001; and RD: 0.07, 95% CI: 0.02, 0.12; p = 0.006, respectively). This study makes several substantial contributions to the body of knowledge and to practical applications. Finally, a number of recommendations are made at the conclusion of this research for the future reference of researchers.


Asunto(s)
Aedes , Humanos , Animales , Temperatura , Mosquitos Vectores , Fiebre , Longevidad
6.
Front Cell Infect Microbiol ; 12: 821061, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35573775

RESUMEN

The Dengue virus (DENV) and Chikungunya virus (CHIKV) are the arboviruses that pose a threat to global public health. Coinfection and antibody-dependent enhancement are major areas of concern during DENV and CHIKV infections, which can alter the clinical severity. Acute hepatic illness is a common manifestation and major sign of disease severity upon infection with either dengue or chikungunya. Hence, in this study, we characterized the coexistence and interaction between both the viruses in human hepatic (Huh7) cells during the coinfection/superinfection scenario. We observed that prior presence of or subsequent superinfection with DENV enhanced CHIKV replication. However, prior CHIKV infection negatively affected DENV. In comparison to monoinfection, coinfection with both DENV and CHIKV resulted in lower infectivity as compared to monoinfections with modest suppression of CHIKV but dramatic suppression of DENV replication. Subsequent investigations revealed that subneutralizing levels of DENV or CHIKV anti-sera can respectively promote the ADE of CHIKV or DENV infection in FcγRII bearing human myelogenous leukemia cell line K562. Our observations suggest that CHIKV has a fitness advantage over DENV in hepatic cells and prior DENV infection may enhance CHIKV disease severity if the patient subsequently contracts CHIKV. This study highlights the natural possibility of dengue-chikungunya coinfection and their subsequent modulation in human hepatic cells. These observations have important implications in regions where both viruses are prevalent and calls for proper management of DENV-CHIKV coinfected patients.


Asunto(s)
Fiebre Chikungunya , Virus Chikungunya , Coinfección , Virus del Dengue , Dengue , Sobreinfección , Línea Celular , Fiebre Chikungunya/complicaciones , Dengue/complicaciones , Humanos
7.
Front Public Health ; 10: 942381, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36051997

RESUMEN

Introduction: Co-infection of coronavirus disease 2019 (COVID-19) and dengue may coexist, as both viruses share similar laboratory and clinical features, making diagnosis and treatment challenging for health care professionals to prescribe, negatively impacting patient prognosis, and outcomes. Results and discussions: Both cases were positive for PCR and X-ray laboratory investigation at clinical examination, confirming COVID-19 and dengue co-infection, admission, and better management in referral hospitals are presented and discussed. The timeline provides detailed cases of situational analysis and the medical actions taken, as well as the outcomes. Conclusion: Both co-infection cases' (patients) health conditions had a poor prognosis and diagnosis and ended with undesired outcomes. Scaling up dual mosquito-vector linked viral diseases surveillance in understanding the transmission dynamics, early diagnosis, and the timely and safe monitoring of case management in clinical and hospital settings nationwide is paramount in curbing preventable co-infections and mortality.


Asunto(s)
COVID-19 , Coinfección , Dengue , Animales , Coinfección/epidemiología , Dengue/diagnóstico , Dengue/epidemiología , Humanos , Arabia Saudita/epidemiología
8.
Front Immunol ; 13: 889196, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35874775

RESUMEN

The dynamics of host-virus interactions, and impairment of the host's immune surveillance by dengue virus (DENV) serotypes largely remain ambiguous. Several experimental and preclinical studies have demonstrated how the virus brings about severe disease by activating immune cells and other key elements of the inflammatory cascade. Plasmablasts are activated during primary and secondary infections, and play a determinative role in severe dengue. The cross-reactivity of DENV immune responses with other flaviviruses can have implications both for cross-protection and severity of disease. The consequences of a cross-reactivity between DENV and anti-SARS-CoV-2 responses are highly relevant in endemic areas. Here, we review the latest progress in the understanding of dengue immunopathogenesis and provide suggestions to the development of target strategies against dengue.


Asunto(s)
COVID-19 , Virus del Dengue , Dengue , Anticuerpos Antivirales , Acrecentamiento Dependiente de Anticuerpo , Humanos
9.
Front Immunol ; 13: 1021016, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36311743

RESUMEN

Dengue virus (DENV) transmitted by the Aedes mosquitoes is the etiological agent of dengue fever, one of the fastest-growing reemerging mosquito-borne diseases on the planet with a 30-fold surge in the last five decades. Interestingly, many arthropod-borne pathogens, including DENV type 2, have been reported to contain an immunogenic glycan galactose-alpha1,3-galactose (alpha-Gal or aGal). The aGal molecule is a common oligosaccharide found in many microorganisms and in most mammals, except for humans and the Old-World primates. The loss of aGal in humans is considered to be an evolutionary innovation for enabling the production of specific antibodies against aGal that could be presented on the glycan of pathogens. The objective of this study was to evaluate different anti-aGal antibodies (IgM, IgG, IgG1, and IgG2) in people exposed to DENV. We observed a significant difference in anti-aGal IgG and IgG1 levels among dengue severity classifications. Furthermore, a significant positive correlation was observed between the anti-aGal IgG and the number of days with dengue symptoms in patients. Additionally, both anti-aGal IgM and IgG levels differ between the two geographical locations of patients. While the anti-aGal IgM and IgG2 levels were not significantly different according to the dengue severity levels, age was negatively correlated with anti-aGal IgM and positively correlated with anti-aGal IgG2. Significant involvement of aGal antibodies in Dengue infection processes is suggested based on the results. Our results open the need for further studies on the exact roles and the mechanisms of the aGal antibodies in Dengue infection.


Asunto(s)
Virus del Dengue , Dengue , Animales , Humanos , Inmunoglobulina G , Inmunoglobulina M , Anticuerpos Antivirales , Galactosa , Primates , Mamíferos
10.
Front Immunol ; 13: 865180, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35799781

RESUMEN

Dengue virus (DENV) is an arboviral disease affecting more than 400 million people annually. Only a single vaccine formulation is available commercially and many others are still under clinical trials. Despite all the efforts in vaccine designing, the improvement in vaccine formulation against DENV is very much needed. In this study, we used a roboust immunoinformatics approach, targeting all the four serotypes of DENV to design a multi-epitope vaccine. A total of 13501 MHC II binding CD4+ epitope peptides were predicted from polyprotein sequences of four dengue virus serotypes. Among them, ten conserved epitope peptides that were interferon-inducing were selected and found to be conserved among all the four dengue serotypes. The vaccine was formulated using antigenic, non-toxic and conserved multi epitopes discovered in the in-silico study. Further, the molecular docking and molecular dynamics predicted stable interactions between predicted vaccine and immune receptor, TLR-5. Finally, one of the mapped epitope peptides was synthesized for the validation of antigenicity and antibody production ability where the in-vivo tests on rabbit model was conducted. Our in-vivo analysis clearly indicate that the imunogen designed in this study could stimulate the production of antibodies which further suggest that the vaccine designed possesses good immunogenicity.


Asunto(s)
Virus del Dengue , Vacunas , Animales , Epítopos , Humanos , Simulación del Acoplamiento Molecular , Péptidos , Conejos , Serogrupo
11.
Front Immunol ; 12: 582935, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33776990

RESUMEN

Severe neurological complications following arbovirus infections have been a major concern in seasonal outbreaks, as reported in the Northeast region of Brazil, where the same mosquito transmitted Zika (ZIKV), Dengue (DENV), and Chikungunya (CHIKV) viruses. In this study, we evaluated the levels of 36 soluble markers, including cytokines, chemokines, growth factors, and soluble HLA-G (Luminex and ELISA) in: i) serum and cerebrospinal fluid (CSF), during the acute phase and two years after the infection (recovery phase, only serum), ii) the relationship among all soluble molecules in serum and CSF, and iii) serum of infected patients without neurological complications, during the acute infection. Ten markers (sHLA-G, IL-10, IL-22, IL-8, MIP-1α, MIP-1ß, MCP-1, HGF, VEGF, and IL-1RA) exhibited differential levels between the acute and recovery phases, with pronounced increases in MIP-1α (P<0.0001), MCP-1 (P<0.0001), HGF (P= 0.0001), and VEGF (P<0.0001) in the acute phase. Fourteen molecules (IL-1ß, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-9, IL-13, IL-15, IL-17A, IFN-α, TNF, and G-CSF) exhibited distinct levels between arbovirus patients presenting or not neurological complications. IL-8, EGF, IL-6, and MCP-1 levels were increased in CSF, while RANTES and Eotaxin levels were higher in serum. Soluble serum (IL-22, RANTES, Eotaxin) and CSF (IL-8, EGF, IL-3) mediators may discriminate putative risks for neurological complications following arbovirus infections. Neurological complications were associated with the presence of a predominant inflammatory profile, whereas in non-complicated patients an anti-inflammatory profile may predominate. Mediators associated with neuroregeneration (EGF and IL-3) may be induced in response to neurological damage. Broad spectrum immune checkpoint molecules (sHLA-G) interact with cytokines, chemokines, and growth factors. The identification of soluble markers may be useful to monitor neurological complications and may aid in the development of novel therapies against neuroinflammation.


Asunto(s)
Biomarcadores/análisis , Citocinas/análisis , Antígenos HLA-G/análisis , Enfermedades del Sistema Nervioso/diagnóstico , Infección por el Virus Zika/diagnóstico , Proteínas de Fase Aguda/análisis , Biomarcadores/sangre , Biomarcadores/líquido cefalorraquídeo , Brasil , Citocinas/sangre , Citocinas/líquido cefalorraquídeo , Femenino , Antígenos HLA-G/sangre , Antígenos HLA-G/líquido cefalorraquídeo , Interacciones Huésped-Patógeno , Humanos , Masculino , Persona de Mediana Edad , Enfermedades del Sistema Nervioso/complicaciones , Recuperación de la Función , Solubilidad , Virus Zika/fisiología , Infección por el Virus Zika/complicaciones , Infección por el Virus Zika/virología
12.
Front Cell Infect Microbiol ; 11: 678945, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34113579

RESUMEN

Dengue virus (DENV) infection has garnered a global interest in the past few decades. Nevertheless, its epidemiology in certain developing and low-income regions remains poorly understood, due to the absence of comprehensive surveillance and reporting systems. This systematic review and meta-analysis aimed to determine the prevalence of DENV infection in the population of Sub-Saharan Africa using DENV infection markers, and to track any changes in its prevalence during the past ten years. It was conducted in accordance with the PRISMA guidelines, targeting the literature available at MEDLINE/PubMed, ScienceDirect, Cochrane library and Google Scholar. All articles published in English language between January 2010 and June 2020 were screened for eligibility. Random effects model was used to calculate the pooled prevalence of all infection markers. The Inconsistency Index (I2) was used to assess the level of heterogeneity between studies. Subgroup analysis according to country and time-frame of studies was conducted to provide possible explanations to substantial heterogeneity. The critical appraisal tool for prevalence studies designed by the Joanna Briggs Institute (JBI) was used to assess the risk of bias in all included studies. A total of 84 articles, covering 21 countries, were included in this review. Quantitative meta-analysis estimated a pooled IgG prevalence of 25% (95% CI: 21-29%, I2 = 99%), a pooled IgM prevalence of 10% (95% CI: 9-11%, I2 = 98%) and a pooled DENV RNA prevalence of 14% (95% CI: 12-16%, I2 = 99%). Evidence for possible publication bias was also found in all three meta-analyses. Subgroup analysis according to the time of sample collection was performed to closely track the changing prevalence of DENV infection markers between 2010 and 2019. This meta-analysis estimates a high prevalence of DENV infection in Sub-Saharan Africa. More cost-efficient vector control strategies should be designed and implemented in order to adapt to the low-resource nature of this region.


Asunto(s)
Dengue , Virosis , África del Sur del Sahara/epidemiología , Estudios Transversales , Dengue/epidemiología , Humanos , Prevalencia
13.
Front Immunol ; 12: 710300, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34394112

RESUMEN

Memory T cells resulting from primary dengue virus (DENV) infection are hypothesized to influence the clinical outcome of subsequent DENV infection. However, the few studies involving prospectively collected blood samples have found weak and inconsistent associations with outcome and variable temporal trends in DENV-specific memory T cell responses between subjects. This study used both ex-vivo and cultured ELISPOT assays to further evaluate the associations between DENV serotype-cross-reactive memory T cells and severity of secondary infection. Using ex-vivo ELISPOT assays, frequencies of memory T cells secreting IFN-γ in response to DENV structural and non-structural peptide pools were low in PBMC from multiple time points prior to symptomatic secondary DENV infection and showed a variable response to infection. There were no differences in responses between subjects who were not hospitalized (NH, n=6) and those who were hospitalized with dengue hemorrhagic fever (hDHF, n=4). In contrast, responses in cultured ELISPOT assays were more reliably detectable prior to secondary infection and showed more consistent increases after infection. Responses in cultured ELISPOT assays were higher in individuals with hDHF (n=8) compared to NH (n=9) individuals before the secondary infection, with no difference between these groups after infection. These data demonstrate an association of pre-existing DENV-specific memory responses with the severity of illness in subsequent DENV infection, and suggest that frequencies of DENV-reactive T cells measured after short-term culture may be of particular importance for assessing the risk for more severe dengue disease.


Asunto(s)
Virus del Dengue/inmunología , Dengue/inmunología , Células T de Memoria/inmunología , Adolescente , Niño , Citocinas/biosíntesis , Dengue/etiología , Femenino , Humanos , Estudios Longitudinales , Masculino , Índice de Severidad de la Enfermedad
14.
Front Immunol ; 11: 1055, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32655548

RESUMEN

Dengue is one of the most frequently transmitted mosquito-borne diseases in the world, which creates a significant public health concern globally, especially in tropical and subtropical countries. It is estimated that more than 390 million people are infected with dengue virus each year and around 96 million develop clinical pathologies. Dengue infections are not only a health problem but also a substantial economic burden. To date, there are no effective antiviral therapies and there is only one licensed dengue vaccine that only demonstrated protection in the seropositive (Immune), naturally infected with dengue, but not dengue seronegative (Naïve) vaccines. In this review, we address several immune components and their interplay with the dengue virus. Additionally, we summarize the literature pertaining to current dengue vaccine development and advances. Moreover, we review some of the factors affecting vaccine responses, such as the pre-vaccination environment, and provide an overview of the significant challenges that face the development of an efficient/protective dengue vaccine including the presence of multiple serotypes, antibody-dependent enhancement (ADE), as well as cross-reactivity with other flaviviruses. Finally, we discuss targeting T follicular helper cells (Tfh), a significant cell population that is essential for the production of high-affinity antibodies, which might be one of the elements needed to be specifically targeted to enhance vaccine precision to dengue regardless of dengue serostatus.


Asunto(s)
Vacunas contra el Dengue/inmunología , Dengue/inmunología , Dengue/prevención & control , Inmunidad Adaptativa , Acrecentamiento Dependiente de Anticuerpo , Reacciones Cruzadas , Dengue/epidemiología , Vacunas contra el Dengue/efectos adversos , Virus del Dengue/inmunología , Desarrollo de Medicamentos/métodos , Desarrollo de Medicamentos/tendencias , Flavivirus/inmunología , Interacciones Microbiota-Huesped/inmunología , Humanos , Inmunidad Innata , Modelos Inmunológicos , Linfocitos T/inmunología
15.
Artículo en Inglés | MEDLINE | ID: mdl-33014899

RESUMEN

Dengue is an acute febrile disease triggered by dengue virus. Dengue is the widespread and rapidly transmitted mosquito-borne viral disease of humans. Diverse symptoms and diseases due to Dengue virus (DENV) infection ranges from dengue fever, dengue hemorrhagic fever (life-threatening) and dengue shock syndrome characterized by shock, endothelial dysfunction and vascular leakage. Several studies have linked the severity of dengue with the induction of inflammasome. DENV activates the NLRP3-specific inflammasome in DENV infected human patients, mice; specifically, mouse bone marrow derived macrophages (BMDMs), dendritic cells, endothelial cells, human peripheral blood mononuclear cells (PBMCs), keratinocytes, monocyte-differentiated macrophages (THP-1), and platelets. Dengue virus mediated inflammasome initiates the maturation of IL-1ß and IL-18, which are critical for dengue pathology and inflammatory response. Several studies have reported the molecular mechanism through which (host and viral factors) dengue induces inflammasome, unravels the possible mechanisms of DENV pathogenesis and sets up the stage for the advancement of DENV therapeutics. In this perspective article, we discuss the potential implications and our understanding of inflammasome mechanisms of dengue virus and highlight research areas that have potential to inhibit the pathogenesis of viral diseases, specifically for dengue.


Asunto(s)
Virus del Dengue , Dengue , Inflamasomas , Animales , Virus del Dengue/patogenicidad , Células Endoteliales , Humanos , Leucocitos Mononucleares , Ratones , Índice de Severidad de la Enfermedad
17.
Rev. salud pública ; Rev. salud pública;14(6): 81-90, nov.-dic. 2012. ilus
Artículo en Español | LILACS | ID: lil-703435

RESUMEN

Objetivo Determinar la frecuencia y severidad del compromiso hepático en niños con Dengue. Métodos Estudio descriptivo que incluyó a 108 niños menores de 13 años con diagnóstico de infección por virus de Dengue, confirmada por detección plasmática de NS1 e IgM dengue-específica, que consultaron al Hospital Universitario de Neiva, en el período de junio de 2009 a mayo de 2010.El grado de daño hepático fue evaluado por criterios clínicos y bioquímicos que incluyeron transaminasas y albúmina. El diagnóstico de infección con Leptospira o Hepatitis A fue realizado por detección de IgM plasmática específica medida en fase aguda y convaleciente. Resultados De los casos incluidos, 98 y 10 casos fueron clasificados como dengue con signos de alarma y Dengue grave, respectivamente. Dos de cada tres pacientes con Dengue presentaron signos de alarma y todos los pacientes con Dengue grave presentaron algún grado de compromiso hapático evidenciado clínica y bioquímicamente. Independientemente de la clasificación clínica, la hepatomegalia fue el signo clínico cardinal del compromiso hepático y se presentó en el 85 % del total de niños incluidos. De resaltar, 5 de los pacientes presentaron probable coinfección de dengue y leptospira, siendo la primera descripción en Colombia. En ninguno de los casos analizados se presentó enfermedad aguda por Hepatitis A. Conclusión El compromiso hepático es muy frecuente en la infección por virus Dengue. Enfermedades como la leptospirosis deben ser tenidas en cuenta no sólo en el diagnóstico diferencial del paciente pediátrico febril con compromiso hepático, sino como causa de coinfección en el niño con Dengue en el sur de Colombia.


Objective Dengue is the most important arthropod-borne viral disease in the world; it can be life-threatening because of liver involvement. Aim Determining liver involvement frequency and severity in dengue-infected children. Methods This was a descriptive case series study which involved studying 108 dengue-infected children aged less than 13 years old whose infection had been confirmed by the detection of dengue-specific IgM and NS1 in plasma. Clinical and biochemical parameters were used for evaluating liver involvement, including transaminases and albumin. Hepatitis A and leptospira infection were also evaluated by using ELISA to detect pathogen-specific IgM in plasma during acute and convalescence phases. The study was carried out at a teaching hospital in Neiva from June 2009 to May 2010. Results Ninety-eight of the aforementioned cases were clinically classified as dengue with warning signs (DWS) and 10 as severe dengue (SD). Two out of three DWS patients and all SD patients had some degree of liver involvement, shown clinically and biochemically. Regardless of the clinical classification, hepatomegaly was the main clinical sign of liver involvement and was present in 85% of all the children in the study. It is worth noting that 5 patients had probable dengue and leptospirosis co-infection, this being the first instance of this in Colombia. None of the cases analyzed here had acute hepatitis A. Conclusions Liver compromise should be considered in confirmed cases of dengue as shown in this series of children. Leptospirosis must be considered as differential diagnosis and also as causing co-infection in a febrile child.


Asunto(s)
Preescolar , Femenino , Humanos , Masculino , Dengue/complicaciones , Hepatopatías/epidemiología , Hepatopatías/etiología , Colombia/epidemiología , Índice de Severidad de la Enfermedad
18.
Recife; s.n; 2014. 65 p. ilus, mapas, tab, graf.
Tesis en Portugués | LILACS | ID: lil-720614

RESUMEN

A dengue é uma arbovirose causada pelo vírus Dengue (DENV), cujos principais vetores são os mosquitos Aedes aegypti e Aedes albopictus. A. aegypti é o único vetor de DENV em Cabo Verde, país que teve a sua primeira epidemia da dengue registrada em 2009. Contudo, pouco se sabe acerca da variação no nível de competência vetorial das populações do vetor aos diferentes sorotipos de DENV. O estudo teve como objetivo avaliar a competência vetorial de A. aegypti da ilha de Santiago, Cabo Verde, a quatro sorotipos de DENV. Para isso, os mosquitos foram alimentados artificialmente com sangue contendo diferentes sorotipos de DENV, e em seguida dissecados ao 7º, 14º e 21º dia após infecção (dpi) para verificar a presença do vírus no intestino, cabeça e glândulas salivares usando a técnica de RT-PCR. Adicionalmente, o número de cópias de RNA viral presente nas glândulas salivares foi determinado por qRT-PCR. Foram observadas altas taxas de infecção das glândulas salivares para DENV-2 e DENV-3 (65 e 75 por cento respectivamente), enquanto que para DENV-1, o RNA viral só foi detectado no intestino e cabeça, não chegando a infectar as glândulas salivares. DENV-4 não disseminou para cabeça e glândulas salivares, mantendo a infecção apenas no intestino (9 por cento). O número de cópias de RNA viral nas glândulas salivares não variou significativamente entre DENV-2 e DENV-3 e nem entre os diferentes períodos de incubação do vírus e títulos de DENV testados. Conclui-se, que a população de Aedes aegypti da ilha de Santiago, Cabo Verde, possui alta competência vetorial para as cepas de DENV-2 e DENV-3 e são pouco susceptíveis para as de DENV-1 e DENV-4. As cópias de RNA viral nas glândulas salivares mantêm-se relativamente constante por 21 dias após a infecção, o que pode potencializar a capacidade vetorial de mosquito A. aegypti e sugere alguma forma de modulação da replicação do vírus nesse órgão


Dengue is an arboviral diseasecaused by dengue virus (DENV), for which the main vectors are the mosquitoes Aedes aegypti andAedes albopictus. A. aegypti is the only DENV vector in Cape Verde, a country which suffered its first dengue outbreak in 2009. However, little is known about the variation in the level of vector competence of this mosquito population to the different DENV serotypes...


Asunto(s)
Aedes , Virus del Dengue , Insectos Vectores/virología , Reacción en Cadena de la Polimerasa , África Occidental
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