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1.
Recurso na Internet em Português | LIS - Localizador de Informação em Saúde | ID: lis-48419

RESUMO

Um microorganismo implantado em mosquitos reduziu em 70% a ocorrência de casos de dengue, 66% de incidência de casos de chinkungunya e 40% de Zika em Niterói, no Rio de Janeiro.


Assuntos
Dengue/prevenção & controle , Zika virus , Planos e Programas de Pesquisa em Saúde , Aedes , Wolbachia
3.
J Med Case Rep ; 15(1): 450, 2021 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-34507614

RESUMO

INTRODUCTION: Coinfection with dengue and hepatitis A is rare and challenging for physicians since their clinical features can be overlapping. These infections are self-limiting but can become complicated by subsequent infective endocarditis. We report a case of infective endocarditis following a coinfection with dengue and hepatitis A. CASE PRESENTATION: A 17-year-old Yemeni male patient was admitted to the hospital complaining of yellowish discoloration of the skin and sclera associated with dark urine and a diffuse skin rash on the trunk and upper limbs followed by intermittent high-grade fever. Coinfection was confirmed by hepatitis A immunoglobulin M and dengue immunoglobulin M. At the time of diagnosis, white blood cells were normal, with mild neutrophilia and thrombocytopenia along with elevated C-reactive protein. Five days later, the patient was readmitted to the emergency department, complaining of high-grade fever, fatigue, myalgia, nausea, and vomiting. A systolic heart murmur was heard, and infective endocarditis was confirmed by the visualization of two vegetations on the mitral valve and coagulase-negative staphylococci after blood culture. Supportive therapies were initiated for hepatitis A and dengue fever, whereas infective endocarditis was treated with antibiotics for 4 weeks. The patient recovered completely from dengue, hepatitis A, and infective endocarditis. CONCLUSION: In endemic areas, it is reasonable to screen for coinfection with dengue and hepatitis A since they are superimposed on each other. Subacute infective endocarditis may occur following initial dengue and hepatitis A coinfection, especially among patients with rheumatic heart disease. An echocardiogram is a pivotal workup for evaluating a patient with persistent fever of unknown origin.


Assuntos
Coinfecção , Dengue , Endocardite Bacteriana , Endocardite , Hepatite A , Adolescente , Dengue/complicações , Dengue/diagnóstico , Endocardite Bacteriana/complicações , Endocardite Bacteriana/diagnóstico , Endocardite Bacteriana/tratamento farmacológico , Hepatite A/complicações , Hepatite A/diagnóstico , Humanos , Masculino
4.
PLoS One ; 16(9): e0257460, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34520486

RESUMO

Dengue is hyperendemic in most Southeast Asian countries including Thailand, where all four dengue virus serotypes (DENV-1 to -4) have circulated over different periods and regions. Despite dengue cases being annually reported in all regions of Thailand, there is limited data on the relationship of epidemic DENV infection between humans and mosquitoes, and about the dynamics of DENV during outbreaks in the northeastern region. The present study was conducted in this region to investigate the molecular epidemiology of DENV and explore the relationships of DENV infection in humans and in mosquitoes during 2016-2018. A total of 292 dengue suspected patients from 11 hospitals and 902 individual mosquitoes (at patient's houses and neighboring houses) were recruited and investigated for DENV serotypes infection using PCR. A total of 103 patients and 149 individual mosquitoes were DENV -positive. Among patients, the predominant DENV serotypes in 2016 and 2018 were DENV-4 (74%) and DENV-3 (53%) respectively, whereas in 2017, DENV-1, -3 and -4 had similar prevalence (38%). Additionally, only 19% of DENV infections in humans and mosquitoes at surrounding houses were serotypically matched, while 81% of infections were serotypically mismatched, suggesting that mosquitoes outside the residence may be an important factor of endemic dengue transmission. Phylogenetic analyses based on envelope gene sequences showed the genotype I of both DENV-1 and DENV-4, and co-circulation of the Cosmopolitan and Asian I genotypes of DENV-2. These strains were closely related to concurrent strains in other parts of Thailand and also similar to strains in previous epidemiological profiles in Thailand and elsewhere in Southeast Asia. These findings highlight genomic data of DENV in this region and suggest that people's movement in urban environments may result in mosquitoes far away from the residential area being key determinants of DENV epidemic dynamics.

5.
J R Soc Interface ; 18(182): 20210565, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34520691

RESUMO

Over 105 million dengue infections are estimated to occur annually. Understanding the disease dynamics of dengue is often difficult due to multiple strains circulating within a population. Interactions between dengue serotype dynamics may result in complex cross-immunity dynamics at the population level and create difficulties in terms of formulating intervention strategies for the disease. In this study, a nationally representative 16-year time series with over 43 000 serotyped dengue infections was used to infer the long-run effects of between and within strain interactions and their impacts on past outbreaks. We used a novel identification strategy incorporating sign-identified Bayesian vector autoregressions, using structural impulse responses, historical decompositions and counterfactual analysis to conduct inference on dengue dynamics post-estimation. We found that on the population level: (i) across-serotype interactions on the population level were highly persistent, with a one time increase in any other serotype associated with long run decreases in the serotype of interest (range: 0.5-2.5 years) and (ii) over 38.7% of dengue cases of any serotype were associated with across-serotype interactions. The findings in this paper will substantially impact public health policy interventions with respect to dengue.

6.
Artigo em Inglês | MEDLINE | ID: mdl-34523165

RESUMO

Dengue fever (DF) is a significant public health problem in the African continent. The primary prevention strategy against the disease is vaccination and entomological control of vectors; however, implementing such a strategy in several countries in the continent is far below what is necessary to control the disease. The Coronavirus disease (COVID-19) pandemic further aggravated this situation and negatively impacted these measures, mainly the coverage of vaccination campaigns, due to restrictive measures to control the disease. Therefore, the most significant risk is that the incidence of DF in the continent will increase even more in the coming years, as a reflection of the negative impact of the pandemic on the control of the disease. To prevent another public health crisis, immediate and multidisciplinary approaches are required to address the epidemiological control of DF in African countries.

7.
J Virol ; : JVI0061021, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34523972

RESUMO

Plasmablasts represent a specialized class of antibody secreting effector B cell population that transiently appear in blood circulation following infection or vaccination. The expansion of these cells generally tends to be massive in patients with systemic infections leading to viral hemorrhagic fevers such as dengue or ebola. To gain a detailed understanding of the human plasmablast responses beyond antibody expression, here we performed immunophenotyping and RNA seq analysis of the plasmablasts from dengue febrile children in India. We found that the plasmablasts expressed several adhesion molecules and chemokines or chemokine receptors that are involved in endothelial interactions or homing to inflamed tissues including skin, mucosa, and intestine; and upregulated expression of several cytokine genes that are involved in leukocyte extravasation and angiogenesis. These plasmablasts also upregulated expression of receptors for several B cell pro-survival cytokines that are known to be induced robustly in systemic viral infections such as dengue, some of which generally tend to be relatively higher in patients manifesting hemorrhage and/or shock compared to patients with mild febrile infection. These findings improve our understanding of human plasmablast responses during the acute febrile phase of systemic dengue infection. Importance Dengue is globally spreading, with over 100 million clinical cases annually, with symptoms ranging from mild self-limiting febrile illness to more severe and sometimes life-threatening dengue hemorrhagic fever or shock, especially among children. The pathophysiology of dengue is complex and remains poorly understood despite many advances indicating a key role for antibody dependent enhancement of infection. While serum antibodies have been extensively studied, the characteristics of the early cellular factories responsible for antibody production, i.e., plasmablasts, are only beginning to emerge. This study provides a comprehensive understanding of the transcriptional profiles of human plasmablasts from dengue patients.

8.
Sci Rep ; 11(1): 18000, 2021 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-34504185

RESUMO

Serologic tests to detect specific IgGs to antigens related to viral infections are urgently needed for diagnostics and therapeutics. We present a diagnostic method for serotype-specific IgG identification of dengue infection by a competitive enzyme-linked immunosorbent assay (ELISA), using high-affinity unnatural-base-containing DNA (UB-DNA) aptamers that recognize the four categorized serotypes. Using UB-DNA aptamers specific to each serotype of dengue NS1 proteins (DEN-NS1), we developed our aptamer-antibody sandwich ELISA for dengue diagnostics. Furthermore, IgGs highly specific to DEN-NS1 inhibited the serotype-specific NS1 detection, inspiring us to develop the competitive ELISA format for dengue serotype-specific IgG detection. Blood samples from Singaporean patients with primary or secondary dengue infections confirmed the highly specific IgG detection of this format, and the IgG production initially reflected the serotype of the past infection, rather than the recent infection. Using this dengue competitive ELISA format, cross-reactivity tests of 21 plasma samples from Singaporean Zika virus-infected patients revealed two distinct patterns: 8 lacked cross-reactivity, and 13 were positive with unique dengue serotype specificities, indicating previous dengue infection. This antigen-detection ELISA and antibody-detection competitive ELISA combination using the UB-DNA aptamers identifies both past and current viral infections and will facilitate specific medical care and vaccine development for infectious diseases.

9.
PLoS One ; 16(9): e0257206, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34506566

RESUMO

Dengue virus (DENV) encodes a unique protease (NS3/NS2B) essential for its maturation and infectivity and, it has become a key target for anti-viral drug design to treat dengue and other flavivirus related infections. Present investigation established that some of the drug molecules currently used mainly in cancer treatment are susceptible to bind non-active site (allosteric site/ cavity) of the NS3 protease enzyme of dengue virus. Computational screening and molecular docking analysis found that dabrafenib, idelalisib and nintedanib can bind at the allosteric site of the enzyme. The binding of the molecules to the allosteric site found to be stabilized via pi-cation and hydrophobic interactions, hydrogen-bond formation and π-stacking interaction with the molecules. Several interacting residues of the enzyme were common in all the five serotypes. However, the interaction/stabilizing forces were not uniformly distributed; the π-stacking was dominated with DENV3 proteases, whereas, a charged/ionic interaction was the major force behind interaction with DENV2 type proteases. In the allosteric cavity of protease from DENV1, the residues Lys73, Lys74, Thr118, Glu120, Val123, Asn152 and Ala164 were involved in active interaction with the three molecules (dabrafenib, idelalisib and nintedanib). Molecular dynamics (MD) analysis further revealed that the molecules on binding to NS3 protease caused significant changes in structural fluctuation and gained enhanced stability. Most importantly, the binding of the molecules effectively perturbed the protein conformation. These changes in the protein conformation and dynamics could generate allosteric modulation and thus may attenuate/alter the NS3 protease functionality and mobility at the active site. Experimental studies may strengthen the notion whether the binding reduce/enhance the catalytic activity of the enzyme, however, it is beyond the scope of this study.

10.
BMC Infect Dis ; 21(1): 940, 2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34507547

RESUMO

BACKGROUND: Dengue virus infection (DVI) is a major health problem in many parts of the world. Its manifestations range from asymptomatic infections to severe disease. Although cardiac involvement has been reported in DVI, its incidence has not yet been well established. METHODS: From July 2016 to January 2018, patients hospitalized at the Hospital for Tropical Diseases, Faculty of Tropical Medicine, Mahidol University, Thailand, with dengue virus infection confirmed by positive NS1 or positive dengue immunoglobulin M findings, participated in the study. We characterized the incidence and change in cardiac function by serial echocardiography and levels of troponin-T and creatine kinase-myocardial band (CK-MB) on the day of admission, the day of defervescence, the first day of hypotension (if any), and at 2 week follow-up. RESULTS: Of the 81 patients evaluated, 6 (7.41%) exhibited elevated biomarker levels. There was no difference in clinical presentation amongst dengue fever, dengue haemorrhagic fever (DHF) and dengue shock syndrome (DSS), except for the amount of bleeding. Cardiac involvement was found in 22.2% of patients: 3 (3.70%) had left ventricular systolic dysfunction, 3 (3.70%) had transient diastolic dysfunction, 6 (7.41%) had increased levels of at least one cardiac biomarker (troponin-T or CK-MB), and 6 (7.41%) had small pericardial effusion. Myocarditis was suspected in only two patients (with DHF); thus, myocarditis was uncommon in patients with dengue virus infection. Three patients developed DSS during admission and were transferred to the intensive care unit. CONCLUSION: Cardiac involvement in adults with dengue infection was common, ranging from elevated cardiac biomarker to myocarditis. Abnormalities in cardiac function had resolved spontaneously by the day of follow-up, without specific treatment. We found that DHF was a significant risk factor for cardiac involvement. Echocardiography is the investigation of choice for evaluating the haemodynamic status of patients with DVI, especially in severe dengue.

11.
IDCases ; : e01284, 2021 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-34513593

RESUMO

We report a 23-year-old pregnant woman who presented with acute high-grade fever, vomiting, and diarrhea for 5 days. She was first hospitalized in RSUD Tangerang-a secondary hospital based in Tangerang and were referred to Cipto Mangunkusumo General Hospital as a tertiary hospital. Initial laboratory results from previous hospital revealed leukopenia, low platelet, elevated aspartate transaminase, and alanine transaminase. Chest radiograph showed no pulmonary infiltration. Reverse transcriptase-PCR (RT-PCR) of the nasopharyngeal swab detected SARS-CoV-2, and NS1 antigen or IgM dengue-specific antibodies were positive. COVID-19 with dengue fever co-infection was diagnosed. Haemorrhagic manifestations were seen in both the mother (gum and gastrointestinal bleeding) and pregnancy (placental abruption). Patient was put on ventilator and was unfortunately lead to her death that were caused by multiorgan dysfunction failure due to co-infection of dengue and COVID-19. Both dengue and COVID-19 had similar manifestation, as it is a warning sign in pregnant patient experienced both that can lead to fatal result in mother and baby. Early diagnosis and management of co-infection is high clinical importance, especially in endemic area of dengue like Indonesia.

12.
Front Cell Infect Microbiol ; 11: 715208, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34513730

RESUMO

Dengue virus (DENV) infection can cause either self-limited dengue fever or hemorrhagic complications. Low platelet count is one of the manifestations of dengue fever. Megakaryocytes are the sole producers of platelets. However, the role of both host and viral factors in megakaryocyte development, maturation, and platelet production is largely unknown in DENV infection. PI3K/AKT/mTOR pathway plays a significant role in cell survival, maturation, and megakaryocyte development. We were interested to check whether pathogenic insult can impact this pathway. We observed decreased expression of most of the major key molecules associated with the PI3K/AKT/mTOR pathway in DENV infected MEG-01 cells. In this study, the involvement of PI3K/AKT/mTOR pathway in megakaryocyte development and maturation was confirmed with the use of specific inhibitors in infected MEG-01 cells. Our results showed that direct pharmacologic inhibition of this pathway greatly impacted megakaryopoiesis associated molecule CD61 and some essential transcription factors (GATA-1, GATA-2, and NF-E2). Additionally, we observed apoptosis in megakaryocytes due to DENV infection. Our results may suggest that DENV impairs PI3K/AKT/mTOR axis and molecules involved in the development and maturation of megakaryocytes. It is imperative to investigate the role of these molecules in the context of megakaryopoiesis during DENV infection to better understand the pathways and mechanisms, which in turn might provide insights into the development of antiviral strategies.

13.
Artigo em Inglês | MEDLINE | ID: mdl-34502007

RESUMO

Dengue is a continuous health burden in Laos and Thailand. We assessed and mapped dengue vulnerability in selected provinces of Laos and Thailand using multi-criteria decision approaches. An ecohealth framework was used to develop dengue vulnerability indices (DVIs) that explain links between population, social and physical environments, and health to identify exposure, susceptibility, and adaptive capacity indicators. Three DVIs were constructed using two objective approaches, Shannon's Entropy (SE) and the Water-Associated Disease Index (WADI), and one subjective approach, the Best-Worst Method (BWM). Each DVI was validated by correlating the index score with dengue incidence for each spatial unit (district and subdistrict) over time. A Pearson's correlation coefficient (r) larger than 0.5 and a p-value less than 0.05 implied a good spatial and temporal performance. Spatially, DVIWADI was significantly correlated on average in 19% (4-40%) of districts in Laos (mean r = 0.5) and 27% (15-53%) of subdistricts in Thailand (mean r = 0.85). The DVISE was validated in 22% (12-40%) of districts in Laos and in 13% (3-38%) of subdistricts in Thailand. The DVIBWM was only developed for Laos because of lack of data in Thailand and was significantly associated with dengue incidence on average in 14% (0-28%) of Lao districts. The DVIWADI indicated high vulnerability in urban centers and in areas with plantations and forests. In 2019, high DVIWADI values were observed in sparsely populated areas due to elevated exposure, possibly from changes in climate and land cover, including urbanization, plantations, and dam construction. Of the three indices, DVIWADI was the most suitable vulnerability index for the study area. The DVIWADI can also be applied to other water-associated diseases, such as Zika and chikungunya, to highlight priority areas for further investigation and as a tool for prevention and interventions.

14.
PLoS One ; 16(9): e0257182, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34507347

RESUMO

BACKGROUND: The dengue vaccine (Dengvaxia) is only recommended for individuals with prior dengue infection (PDI). This study aimed to perform a serosurvey to inform decision-making for vaccine introduction and identify appropriate target populations. We also evaluated the performance of the serological tests using plaque reduction neutralization test (PRNT) as a reference test in identifying PDI to determine suitability for pre-vaccination screening. METHODS: We enrolled 115 healthy individuals between 10 and 22 years of age living in the Ratchaburi province of Thailand. The serum samples were tested by PRNT to measure the prevalence and concentration of serotype-specific neutralizing antibodies. The performance of the IgG rapid diagnostic test (RDT, SD Bioline, Korea) and IgG enzyme-linked immunosorbent assay (ELISA, EUROIMMUN, Germany) in identifying PDI were evaluated by using PRNT as a reference method. RESULTS: Ninety-four (81.7%) individuals neutralized one or more dengue serotypes at a titer threshold greater than or equal to 10. Multitypic profiles were observed in 70.4% of the samples which increased to 91.9% in subjects aged 19-22. Among monotypic samples, the highest proportion was reactive against DENV-1 followed by DENV-2, DENV-3, and DENV-4. The highest anti-dengue antibody titers were recorded against DENV-1 and increased with age to a geometric mean NT50 titer (GMT) of 188.6 in the 19-22 age group. While both RDT and ELISA exhibited 100% specificity, RDT demonstrated low sensitivity (35%) with ELISA displaying much greater sensitivity (87%). CONCLUSIONS: Almost 80% of adolescents and youth in Ratchaburi province had already been exposed to one or more of the dengue virus serotypes. The dengue IgG RDT displayed low sensitivity and is likely not be suitable for dengue pre-vaccination screening. These results support the use of IgG ELISA test for dengue vaccination in endemic areas.

15.
Med J Malaysia ; 76(5): 750-752, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34508389

RESUMO

Dengue fever (DF) is an important public health problem, and it is now endemic in more than 100 countries worldwide. Dengue associated neurological complication is estimated to be affecting 0.5 to 6.2% of patients. Even though this is rare, neurological manifestation of DF is an increasingly recognized entity in recent years due to significant mortality and morbidity reported/seen. Reported central nervous system manifestations due to dengue include encephalitis, encephalopathy, myelitis, myositis, acute disseminated encephalomyelitis, Guillain-Barré syndrome, stroke and etc. We report here a case of acute necrotizing encephalopathy secondary to DF in a previously healthy 12-year-old girl.

16.
J Ethnopharmacol ; : 114627, 2021 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-34509603

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Dengue virus (DENV) is a re-emerging mosquito-borne Flavivirus that has recently engendered large epidemics around the world. Consequently antivirals with effective anti-DENV therapeutic activity are urgently required. In the 18th century, Europeans, as well as native inhabitants of North America, were known to adapt the medicinal property of the common perennial plant Eupatorium perfoliatum L. to treat fever and infections. Previous studies have shown that Eupatorium perfoliatum L. possesses anti-inflammatory, anti-oxidative, anti-plasmodial, anti-bacterial and antiviral activities. However, to the best of our knowledge, no anti-DENV activity of E. perfoliatum L. had been investigated at the molecular level so far. AIM OF STUDY: Here, first time we have attempted to study the action of E. perfoliatum extract and its few bioactive components i.e., quercetin, caffeic acid and eupafolin against wild primary clinical isolate of DENV-2 infection in an in vitro model. MATERIALS AND METHODS: The presence of the bioactive components in the E. perfoliatum extract, were analyzed by HPLC- DAD. Then, CC50 as well as IC50 values of the extract and its bioactive components were measured against DENV in HepG2 cell line. After that, the antiviral activity was studied by Time of addition assay using qRT-PCR. Further, the downstream signalling action of E. perfoliatum extract, was studied by Human phosphorylation MAPK antibody array, followed by immunofluorescence microscopy. Moreover, a molecular docking analysis was done to study the binding affinity of bioactive components of E. perfoliatum extract with TIM-1 transmembrane receptor protein, which is known for viral internalization. RESULT: We found that E. perfoliatum extract has marked antiviral activity during pre-treatment against DENV infection in HepG2 cell line. The extract also significantly reduced the DENV induced autophagy in HepG2 cell line as detected by LC3 II localization. The presence of different bioactive compounds in E. perfoliatum extract were confirmed by HPLC-DAD. In the bioactive components, in parallel to earlier studies, quercetin showed the most significant preventive action against DENV infection. Further, in molecular docking analysis also, quercetin showed the strongest binding affinity towards DENV membrane receptor TIM-1 protein. CONCLUSION: Our findings suggests that E. perfoliatum extract has significant potential to be an anti-DENV therapeutic agent. Moreover, among the bioactive components, quercetin may have a prophylaxis role in executing the antiviral activity of E. perfoliatum extract against DENV infection.

17.
J Travel Med ; 2021 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-34510205

RESUMO

BACKGROUND: Dengue is the most prevalent and rapidly spreading mosquito-borne viral disease. We present the global, regional, and national burden of dengue from 1990 to 2019 based on the findings from the Global Burden of Diseases, Injures, and Risk Factors Study 2019 (GBD 2019). METHODS: Based upon GBD 2019 dengue data on age-standardized incidence rate (ASIR), age-standardized death rate (ASDR) and age-standardized disability-adjusted life years (DALYs) rate, this study estimates and presents annual percentage change (EAPC) to quantify trends over time to assess potential correlates of increased dengue activity such as global travel, and warming. RESULTS: Globally from 1990 to 2019, dengue incident cases, deaths and DALYs gradually increased. Those under 5, once accounting for the largest portion of deaths and DALYs in 1990, were eclipsed by those 15-49 years old in 2019. Age standardized incidence (ASIR: EAPC 3.16, 95%CI: 2.90-3.43), death (ASDR: EAPC 5.42, 95%CI: 2.64-8.28), and DALY rates (EAPC 2.31, 95%CI: 2.00-2.62) accelerated most among high-middle and high socio-demographic index (SDI) regions. Southeast Asia and South Asia had most of the dengue incident cases, deaths and DALYs, but East Asia had the fastest rise in ASIR (EAPC 4.57, 95%CI: 4.31, 4.82), while Tropical Latin America led in ASDR (EAPC 11.32, 95%CI: 9.11, 13.58) and age-standardized DALYs rate (EAPC 4.13, 95%CI: 2.98, 5.29). SDI showed consistent bell shape relationship with ASIR, ASDR and age-standardized DALYs rate. Global Land-Ocean Temperature Index and air passenger travel metrics were found to be remarkably positively correlated with dengue burden. CONCLUSIONS: The burden of dengue has become heavier from 1990 to 2019, amidst the three decades of urbanization, warming climates and increased human mobility in much of the world. Southeast Asia and South Asia remain regions of concern, especially in conjunction with the Americas swift rise in dengue burden.

18.
Sci Rep ; 11(1): 17542, 2021 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-34475493

RESUMO

The global incidence of dengue, which is caused by dengue virus (DENV) infection, has grown dramatically in recent decades and secondary infection with heterologous serotype of the virus may cause severe symptoms. Efficacious dengue vaccines should be able to provide long-lasting immunity against all four DENV serotypes simultaneously. In this study, we constructed a novel vaccine platform based on tetravalent dengue virus-like particles (DENV-LPs) in which envelope (E) protein carried a FLAG tag sequence at the position located not only in the exterior loop on the protruding domain but outside of dimerization interface of the protein. We demonstrated an effective strategy to produce the DENV-LPs by transient transfection with expression plasmids for pre-membrane and E proteins of DENV-1 to DENV-4 in mammalian cells and to concentrate and purify them with one-step affinity chromatography. Characteristic features of VLPs such as particle size, shape and density were comparable to flavivirus-like particles reported. The neutralizing activity against all four DENV serotypes was successfully induced by immunization with the purified tetravalent VLPs in mice. Simple, one-step purification systems for VLP vaccine platforms using epitope-tagging strategy should be advantageous for vaccine development not only for dengue but for emerging pandemics in the future.

19.
BMC Infect Dis ; 21(1): 893, 2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34465288

RESUMO

BACKGROUND: Several studies have reported a significant association of knowledge, attitude and preventive practice (KAP) regarding dengue infection among community's resident in endemic areas. In this study we aimed to assess and develop a reliable and valid KAP survey on the subject of dengue that is suitable for the resident population of Sabah, Malaysia. METHODS: A community-based cross-sectional study was conducted from October 2019 to February 2020 involving 468 respondents. Information on the socio-demographic characteristics of the participants (six items), their KAP (44, 15 and 18 items on knowledge, attitude and practice, respectively) and treatment-seeking behaviour (five items) towards dengue was collected using a structured questionnaire. Data analysis was performed using SPSS and R software in the R Studio environment. The knowledge section was analysed by two-parameter logistic item response theory (2-PL IRT) using ltm package. The construct validity and reliability of items for sections on attitude, practice and treatment-seeking behaviour were analysed using psy package. RESULTS: For the knowledge section, only 70.5% (31/44) of items were within or close to the parameter acceptable range of -3 to + 3 of difficulty. In terms of discrimination, 65.9% (29/44) of items were within or close to the acceptable range of 0.35 to 2.5, and 24 items (54.5%) failed to fit the 2-PL IRT model (P < 0.05) after assessing by goodness-of-fit analysis. Only eight items were reliable and retained in the attitude section with a Kaiser-Meyer-Olkin (KMO) test value of > 0.7, while based on the communalities, 11 items in the attitude section were excluded due to very low h2, factor loading values and low correlation with the total (< 0.5). The practice section was found suitable for factor analysis because the KMO value was > 0.7. The communalities of the practice section showed that seven items had low h2 values (< 0.3), which were therefore excluded from further analysis, and only 11 items were retained. CONCLUSIONS: The KAP items retained in the final version of the survey were reliable and valid to be use as a questionnaire reference when conducting future similar studies among the population of Sabah.

20.
J Assoc Physicians India ; 69(4): 11-12, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34470195

RESUMO

We report a case with serologically (MAC ELISA) proven acute dengue virus infection and variable atrio-ventricular (AV) conduction block (2:1 with Mobitz type I second degree). A 23 years old boy was referred to the hospital on the 7th day of the illness for thrombocytopenia (19000/cmm) with fever and body aches. On day 11th of the illness, during recovery phase he developed variable AV conduction block. There was no other abnormality in the 12-lead electrocardiogram (ECG) except occasional VPCs and echocardiogram showed normal ventricular systolic function. CPK-MB, serum electrolytes were normal. Trop-T was negative. The pulse and rhythm resolved to normal on day 13th. AV block during recovery from dengue fever may be a transient functional phenomenon, in which altered autonomic tone may play a role and conservative but vigilant management may be justified.


Assuntos
Bloqueio Atrioventricular , Dengue , Adulto , Bloqueio Atrioventricular/diagnóstico , Dengue/complicações , Dengue/diagnóstico , Ecocardiografia , Eletrocardiografia , Frequência Cardíaca , Humanos , Masculino , Adulto Jovem
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