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Seroprevalence and incidence of primary dengue infections among children in a rural region of Maharashtra, Western India.

BMC Infect Dis; 19(1): 296, 2019 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-30940086


BACKGROUND: Dengue infections have become a huge threat to public health systems in developing countries. Data on seroprevalence and incidence of dengue infections are lacking from rural regions of India. The objective of present study was to investigate the seroprevalence and incidence of dengue infection utilizing repeated serosurveys from a rural region of Maharashtra, Western India. METHODS: In the present study, 819 children between ages 5 to 15 years from 21 villages in Pune District of Maharashtra, India were sampled in 2014 and 2016. The sera were tested for the presence of dengue specific IgG using an indirect IgG ELISA kit. RESULTS: Overall seroprevalence of dengue was 15.3% (95% confidence intervals (CI) 12.9-17.8%) in 2014 and 20.5% (95% CI 17.8-23.4%) in 2016. Among the 694 children who were seronegative at baseline (2014), 78 seroconverted. Overall incidence rate of primary dengue was 54.2 infections/1000 children years (95% CI 43.0-67.3). Incidence of primary dengue infection was higher in children from urbanized villages compared to rural villages (Incidence rate ratio (IRR) 2.6 (95% CI 1.3-5.2)). In rural villages, incidence of primary dengue infection was higher in children aged 10 years or above as compared to those aged below 10 years (IRR 9.75 (95% CI 1.21-77.9). CONCLUSIONS: The study provides the incidence rates of primary dengue infections from a rural region of India. More multi centric studies investigating the incidence of dengue will provide accurate estimate of incidence of dengue and help formulate well directed policies. The results also suggest that urbanization and transitions in demographic settings might favour dengue outbreaks in rural regions and these regions need to be targeted for vector control measures.

Optimal dengue vaccination strategies of seropositive individuals.

Math Biosci Eng; 16(3): 1171-1189, 2019 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-30947414


The dengue vaccine, CYD-TDV (Dengvaxia), has been licensed in 20 countries in Latin America and Southeast Asia beginning in 2015. In April 2018, the World Health Organization (WHO) advised that CYD-TDV should only be administered to individuals with a history of previous dengue virus infection. Using literature-based parameters, a mathematical model of dengue transmission and vaccination was developed to determine the optimal vaccination strategy while considering the effect of antibody-dependent enhancement (ADE). We computed the optimal vaccination rates under various vaccination costs and serological profiles. We observe that the optimal dengue vaccination rates for seropositive individuals are highest at the initial phase of a vaccination program, requiring intense effort at the early phase of an epidemic. The model shows that even in the presence of ADE, vaccination could reduce dengue incidence and provide population benefits. Specifically, optimal vaccination rates increase with a higher proportion of monotypic seropositive individuals, resulting in a higher impact of vaccination. Even in the presence of ADE and with limited vaccine efficacy, our work provides a population-level perspective on the potential merits of dengue vaccination.

Predictive value of persistent NS1 antigen positivity beyond 3rd day for dengue haemorrhagic fever in Sri Lankan children.

BMC Res Notes; 12(1): 214, 2019 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-30961645


OBJECTIVE: Dengue haemorrhagic fever (DHF) is a major public health concern responsible for significant morbidity in both adult and paediatric populations in Sri Lanka. This study examined if persistent non structural protein 1 (NS1) antigen positivity beyond day 3 was predictive of the occurrence of dengue haemorrhagic fever. The patients were followed up during their in-hospital stay and the severity of the illness was classified according to the WHO classification. The NS1 antigen test was repeated after day 3 of the onset of illness, at least 2 days after the initial test. RESULTS: One hundred and fifty-seven patients were enrolled. Persistent NS1 antigen test positivity after day 3 of the illness was not predictive of subsequent development of DHF. Out of multiple other demographic and illness related factors assessed, only having a secondary dengue infection was associated with a high risk of DHF (relative risk = 3.077, 95% CI 1.361, 6.954). Persistent NS1 positivity on day 3 may not be indicative of disease severity. However results need to be confirmed by a larger study with quantitative NS1 testing.

Drug repurposing of N-acetyl cysteine as antiviral against dengue virus infection.

Antiviral Res; 166: 42-55, 2019 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-30928439


Liver injury is one of the hallmark features of severe dengue virus (DENV) infection since DENV can replicate in the liver and induce hepatocytes to undergo apoptosis. N-acetyl cysteine (NAC), which is a clinically-used drug for treating acetaminophen toxicity, was found to benefit patients with DENV-induced liver injury; however, its mechanism of action remains unclear. Accordingly, our aim was to repurpose NAC in the preclinical studies to investigate its mechanism of action. Time of addition experiments in HepG2 cells elucidated effectiveness of NAC to reduce infectious virion at pre-, during- and post infection. In DENV-infected mice, NAC improved DENV-associated clinical manifestations, including leucopenia and thrombocytopenia, and reduced liver injury and hepatocyte apoptosis. Interestingly, we discovered that NAC significantly reduced DENV production in HepG2 cells and in liver of DENV-infected mice by induction of antiviral responses via interferon signaling. NAC treatment in DENV-infected mice helped to maintain antioxidant enzymes and redox balance in the liver. Therefore, NAC reduces DENV production and oxidative damage to ameliorate DENV-induced liver injury. Taken together, these findings suggest the novel therapeutic potential of NAC in DENV-induced liver injury and recommend evaluating its efficacy and safety in humans with DENV-induced liver injury.

Simultaneous detection of Dengue virus, Chikungunya virus, Zika virus, Yellow fever virus and West Nile virus.

J Virol Methods; 268: 53-55, 2019 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-30930286


Although certain mosquito-borne virus, such as Dengue virus (DENV), Chikungunya virus (CHIKV), Zika virus (ZIKV), Yellow fever virus (YFV) and West Nile virus (WNV), are an important public health concern in those countries where transmitter mosquitoes are endemic, several cases of travelers from those endemic countries have been recently reported in Europe. Thus, early diagnosis of these viruses is essential for patient management and adoption of preventive measures. An assay for the simultaneous detection of DENV, CHIKV, ZIKV, YFV and WNV based on a multiplex real-time (RT)-PCR and its usefulness for diagnosis in infection screenings and surveillance of arbovirus in non-endemic countries are described.

Nationally-representative serostudy of dengue in Bangladesh allows generalizable disease burden estimates.

Elife; 82019 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-30958263


Serostudies are needed to answer generalizable questions on disease risk. However, recruitment is usually biased by age or location. We present a nationally-representative study for dengue from 70 communities in Bangladesh. We collected data on risk factors, trapped mosquitoes and tested serum for IgG. Out of 5,866 individuals, 24% had evidence of historic infection, ranging from 3% in the north to >80% in Dhaka. Being male (aOR:1.8, [95%CI:1.5-2.0]) and recent travel (aOR:1.3, [1.1-1.8]) were linked to seropositivity. Using catalytic models, we estimate that 40 million [34.3-47.2] people have been infected with 2.4 million ([1.3-4.5]) annual infections. Had we visited only 20 communities, seropositivity estimates would have ranged from 13% to 37%, highlighting the lack of representativeness generated by small numbers of communities. Our findings have implications for both the design of serosurveys and tackling dengue in Bangladesh.

The Dengue ED3 Dot Assay, a Novel Serological Test for the Detection of Denguevirus Type-Specific Antibodies and Its Application in a Retrospective Seroprevalence Study.

Viruses; 11(4)2019 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-30934772


There are four distinct antigenic serotypes of dengue viruses (DENV-1-4). Sequential infections with different serotypes lead to crossreactive but also serotypespecific neutralizing antibody responses. Neutralization assays are considered as gold standard for serotype-specific antibody detection. However, for retrospective seroprevalence studies, access to large serum quantities is limited making neutralization assays well-nigh impossible. Therefore, a serological test, wasting only 10 µL serum, was developed using fusion proteins of maltose binding protein and E protein domain 3 (MBP-ED3) as antigens. Twelve MBP-ED3 antigens for DENV-1-4, three MBP-ED3 antigens for WNV, JEV, and TBEV, and MBP were dotted onto a single nitrocellulose strip. ED3 dot assay results were compared to virus neutralization and ED3 ELISA test results, showing a >90% accordance for DENV-1 and a 100% accordance for DENV-2, making the test specifically useful for DENV-1/-2 serotype-specific antibody detection. Since 2010, DENV-1 has replaced DENV-2 as the dominant serotype in Cambodia. In a retrospective cohort analysis, sera collected during the DENV-1/-2 endemic period showed a shift to DENV-2-specific antibody responses in 2012 paralleled by the decline of DENV-2 infections. Altogether, the ED3 dot assay is a serum-, time- and money-saving diagnostic tool for serotype-specific antibody detection, especially when serum samples are limited.

Impacts of Hurricanes Irma and Maria on Populations, Aquatic Habitats, and Mosquito Infections with Dengue, Chikungunya, and Zika Viruses in Puerto Rico.

Am J Trop Med Hyg; 2019 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-30963992


Puerto Rico was severely impacted by Hurricanes Irma and Maria in September 2017. The island has been endemic for dengue viruses (DENV) and recently suffered epidemics of chikungunya (CHIKV 2014) and Zika (ZIKV 2016) viruses. Although severe storms tend to increase the number of vector and nuisance mosquitoes, we do not know how they influence populations and arboviral transmission. We compared the abundance of female in autocidal gravid ovitraps (AGO traps), container habitats, and presence of RNA of DENV, CHIKV, and ZIKV in this vector before and after the hurricanes in Caguas city and in four communities in southern Puerto Rico. Two of these communities were under vector control using mass AGO trapping and the other two nearby communities were not. We also investigated mosquito species composition and relative abundance (females/trap) using BG-2 traps in 59 sites in metropolitan San Juan city after the hurricanes. Mosquitoes sharply increased 5 weeks after Hurricane Maria. Ensuing abundance of was higher in Caguas and in one of the southern communities without vector control. did not significantly change in the two areas with vector control. The most abundant mosquitoes among the 26 species identified in San Juan were ( ) spp., , , and . No arboviruses were detected in following the hurricanes, in contrast with observations from the previous year, so that the potential for -borne arboviral outbreaks following the storms in 2017 was low.

Lack of Evidence of Sylvatic Transmission of Dengue Viruses in the Amazon Rainforest Near Iquitos, Peru.

Artigo em Inglês | MEDLINE | ID: mdl-30964397


Dengue viruses (DENV) are currently responsible for more human morbidity and mortality than any other known arbovirus, and all four DENV are known to exist in sylvatic cycles that might allow these viruses to persist if the urban (Aedes aegypti) cycle could be controlled. To determine whether DENV were being maintained in a sylvatic cycle in a forested area about 14 km southwest of Iquitos, Peru, a city in which all 4 serotypes of DENV circulate, we placed 20 DENV seronegative Aotus monkeys in cages either in the canopy or near ground level for a total of 125.6 months. Despite capturing >66,000 mosquitoes in traps that collected some of the mosquitoes attracted to these monkeys, blood samples obtained once a month from each animal were tested and found to be negative by an enzyme-linked immunosorbent assay for IgM and IgG antibodies to dengue, yellow fever, Venezuelan equine encephalitis, Oropouche, and Mayaro viruses. Although all four DENV serotypes were endemic in nearby Iquitos, the findings of this study did not support a DENV sylvatic maintenance and transmission cycle in a selected area of the Amazon rainforest in northeastern Peru.

Abiotic factors and population dynamic of Aedes aegypti and Aedes albopictus in an endemic area of dengue in Brazil.

Rev Inst Med Trop Sao Paulo; 61: e18, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30970109


Aedes aegypti and Aedes albopictus are exotic species in the Americas with high epidemiological relevance as they are vectors of many pathogens. This study aimed at understanding the population dynamics of A. aegypti and A. albopictus and the influence of abiotic factors in an endemic area of dengue. The study was conducted in the urban area of Campo Grande, Mato Grosso do Sul, Brazil, over one year. In seven regions of the city, 50 ovitraps were installed in each neighborhood. The development of the larvae was monitored under controlled laboratory conditions until they reached the adult phase. A total of 50,900 eggs of Aedes sp. were collected, 26,073 of which reached adulthood: 25,496 (97.8 %) A. aegypti and 540 (2.1%) A. albopictus. A. aegypti was observed in all months during the study. The highest number of A. albopictus eggs were collected in June, while in August and September, an absence of this species was noted. Abiotic factors such as temperature, humidity and rainfall were responsible for the observed fluctuations in the mosquito population. The presence of A. albopictus in the urban area of the city is concerning because it could become a potential vector for other arboviruses that afflict human populations. The occurrence of these species in Campo Grande reinforces the need for constant entomological and epidemiological surveillance so that informed actions could be taken to decrease potential breeding sites.

Annexin II as a Dengue Virus Serotype 2 Interacting Protein Mediating Virus Interaction on Vero Cells.

Viruses; 11(4)2019 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-30970587


Recent evidence has demonstrated that dengue virus requires active filopodia formation for a successful infection. However, the cellular factor involved in the interaction has not been fully elucidated. We used a combination of virus overlay protein binding assay and LC-MS/MS, and identified annexin II as a dengue virus serotype 2 (DENV2) interacting protein on Vero cells, upon filopodia induction. Flow cytometry analysis showed annexin II on the Vero cells surface increased when DENV2 was added. The amount of annexin II in the plasma membrane fraction was reduced as the infection progressed. Antibody-mediated inhibition of infection and siRNA-mediated knockdown of annexin II expression significantly reduced DENV2 infection and production levels. Collectively, we demonstrated that annexin II is one of the host factor involved in DENV2 binding on Vero cells.

Development of Dengue-type NS1 ELISA for Rapid Detection and Differentiation of Dengue Serotypes during Early Infection.

J Clin Microbiol; 2019 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-30971466


Dengue fever, caused by infections with the dengue virus (DENV), affects nearly four hundred million people globally every year. Early diagnosis and management can reduce the morbidity and mortality rates of severe forms of dengue disease as well as decrease the risk of wider outbreaks. Although early diagnosis of dengue can be achieved using a number of commercial NS1 detection kits, none of these can differentiate among the four dengue virus serotypes. In this study, we developed a Dengue-type NS1 ELISA by pairing a serotype-cross-reactive mAb with one of four serotype-specific mAbs in order to facilitate the rapid detection of NS1 antigens and the simultaneous differentiation of dengue serotypes. A total of 146 serum samples obtained from patients suspected to be in the acute phase of dengue infection were used to evaluate the clinical application of our novel test for the detection and serotyping of DENV. The overall sensitivity rate of our test was 84.85%, and the sensitivity rates for serotyping were as follows: DENV1 (88.2%, 15/17), DENV2 (94.7%, 18/19), DENV3 (75%, 12/16), and DENV4 (66.6%, 6/9). Moreover, there was no cross-reactivity among serotypes, and no cross-reactivity was observed in sera from non-dengue patients. Thus, our test not only enables the rapid detection of the dengue virus, but it can also distinguish among specific serotypes during the early stages of infection. These results indicate that our Dengue-type NS1 ELISA is a convenient tool that may help elucidate the epidemiology of dengue outbreaks and facilitate the clinical management of dengue infections.

Isolation and characterization of exosomes released from mosquito cells infected with dengue virus.

Virus Res; 266: 1-14, 2019 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-30930201


Exosomes are endocytic origin small-membrane vesicles secreted to the extracellular space by most cell types. Exosomes released from virus infected-cells can mediate the cell-to-cell communication to promote or modulate viral transmission. Dengue virus (DENV) is an arbovirus transmitted by Aedes mosquitoes bite to humans. Interestingly, the role of exosomes during the DENV infection in mammalian cells has already been described. However, little is known about exosomes derived from infected mosquito cells. Thus, the exosomes released from DENV-infected C6/36 cells were isolated, purified and analyzed using an antibody against the tetraspanin CD9 from human that showed cross-reactivity with the homologs to human CD9 found in Aedes albopictus (AalCD9). The exosomes from DENV infected cells were larger than the exosomes secreted from uninfected cells, contained virus-like particles, and they were able to infect naïve C6/36 cells, suggesting that exosomes are playing a role in virus dissemination.

Evaluation of biochemical and haematological changes in dengue fever and dengue hemorrhagic fever in Sri Lankan children: a prospective follow up study.

BMC Pediatr; 19(1): 87, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30935373


BACKGROUND: Series of biochemical and haematological changes occur during the course of dengue infection, which vary depending on the clinical disease. The patterns of change are not well documented and identifying these patterns in children with dengue infection would help to anticipate the progression to different clinical stages thus enabling effective management. METHODS: A prospective follow up study was conducted during the period of July 2013 - April 2014 at Professorial Pediatric unit, Lady Ridgeway Hospital for Children, Colombo, Sri Lanka. Children (5-12 years) admitted within the first 84 h of fever, with a clinical diagnosis of dengue infection were recruited. Children who became positive for dengue IgM were included in the final analysis. Blood was collected on admission for complete blood count, Alanine aminotransferase, Aspartate aminotransferase, albumin, cholesterol and corrected calcium. These tests were repeated at 12 hourly intervals during the hospital stay. RESULTS: Data of 130-subjects were analyzed (Dengue fever /Dengue hemorrhagic fever: 100/30). There was a significant difference in the pattern of white cell counts, platelets and haematocrit in the two clinical groups. Both transaminase rose initially in both dengue fever and dengue hemorrhagic fever and a steep rise were seen between 8th and 9th days in hemorrhagic fever. Both albumin and cholesterol decreased significantly at the time of entering into the critical phase. According to Receiver operating characteristic curve analysis, albumin level crossing 37.5g/L (sensitivity 86.7%, specificity 77.8%) and a 0.38 mmol/L reduction in cholesterol level (sensitivity 77.3%, specificity 71.9%) between day 3 and 4 were the best predictors of entering into critical phase. Calcium levels did not show any distinct pattern. CONCLUSIONS: There is a clear difference in the pattern of change of both hematological and biochemical parameters in dengue fever and dengue hemorrhagic fever. Reduction in albumin and cholesterol levels seen between the completion of day 3 and day 4 were highly valid predictors of entering into critical phase in dengue hemorrhagic fever.

Target and non-target botanical pesticides effect of Trichodesma indicum (Linn) R. Br. and their chemical derivatives against the dengue vector, Aedes aegypti L.

Artigo em Inglês | MEDLINE | ID: mdl-30977009


The effects of crude ethanol derived leaf extract Trichodesma indicum (Linn) (Ex-Ti) and their chief derivatives were accessed on the survival and development of the dengue mosquito Ae. aegypti also their non-toxic activity against mosquito predator. T. indicum is recognized to be the vital weed plant and a promising herb in the traditional ayurvedic medicine. In this study, the GC-MS chromatogram of Ex-Ti showed higher peak area percentage for cis-10-Heptadecenoic acid (21.83%) followed by cycloheptadecanone (14.32%). The Ex-Ti displayed predominant mortality in larvae with 96.45 and 93.31% at the prominent dosage (200 ppm) against III and IV instar. Correspondingly, sub-lethal dosage against the enzymatic profile of III and IV instar showed downregulation of α,ß-carboxylesterase and SOD protein profiles at the maximum concentration of 100 ppm. However, enzyme level of GST as well as CYP450 increased significantly dependent on sub-lethal concentration. Likewise, fecundity and hatchability of egg rate of dengue mosquito decreased to the sub-lethal concentration of Ex-Ti. Repellent assay illustrates that Ex-Ti concentration had greater protection time up to 210 min at 100 ppm. Also, activity of Ex-Ti on adult mosquito displayed 100% mortality at the maximum dosage of 600, 500 and 400 ppm within the period of 50, 60 and 70 min, respectively. Photomicrography screening showed that lethal dosage of Ex-Ti (100 ppm) produced severe morphological changes with dysregulation in their body parts as matched to the control. Effects of Ex-Ti on the Toxorhynchites splendens IV instar larvae showed less mortality (43.47%) even at the maximum dosage of 1500 ppm as matched to the chemical pesticide Temephos. Overall, the present research adds a toxicological valuation on the Ex-Ti and their active constituents as a larvicidal, repellent and adulticidal agents against the global burdening dengue mosquito.

Dengue and Zika Virus 5' Untranslated Regions Harbor Internal Ribosomal Entry Site Functions.

MBio; 10(2)2019 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-30967466


The genus of the family encompasses numerous enveloped plus-strand RNA viruses. Dengue virus (DENV), a flavivirus, is the leading cause of serious arthropod-borne disease globally. The genomes of DENV, like the genomes of yellow fever virus (YFV), West Nile fever virus (WNV), or Zika virus (ZIKV), control their translation by a 5'-terminal capping group. Three other genera of are remarkable because their viruses use internal ribosomal entry sites (IRESs) to control translation, and they are not arthropod transmitted. In 2006, E. Harris' group published work suggesting that DENV RNA does not stringently need a cap for translation. They proposed that instead DENV translation is controlled by an interplay between 5' and 3' termini. Here we present evidence that the DENV or ZIKV 5' untranslated regions (5'-UTRs) alone have IRES competence. This conclusion is based, first, on the observation that uncapped monocistronic mRNAs 5' terminated with the DENV or ZIKV 5'-UTRs can efficiently direct translation of a reporter gene in BHK and C6/36 cells and second, that either 5'-UTR placed between two reporter genes can efficiently induce expression of the downstream gene in BHK cells but not in C6/36 cells. These experiments followed observations that uncapped DENV/ZIKV genomic transcripts, 5' terminated with pppAN… or GpppAN…, can initiate infections of mammalian (BHK) or mosquito (C6/36) cells. IRES competence of the 5'-UTRs of DENV/ZIKV raises many open questions regarding the biology and control, as well as the evolution, of insect-borne flaviviruses. Members of the genus of are important human pathogens of great concern because they cause serious diseases, sometimes death, in human populations living in tropical, subtropical (dengue virus [DENV], Zika virus [ZIKV], and yellow fever virus), or moderate climates (West Nile virus). Flaviviruses are known to control their translation by a cap-dependent mechanism. We have observed, however, that the uncapped genomes of DENV or ZIKV can initiate infection of mammalian and insect cells. We provide evidence that the short 5' untranslated region (5'-UTR) of DENV or ZIKV genomes can fulfill the function of an internal ribosomal entry site (IRES). This strategy frees these organisms from the cap-dependent mechanism of gene expression at an as yet unknown stage of proliferation. The data raise new questions about the biology and evolution of flaviviruses, possibly leading to new controls of flavivirus disease.

3-Trifluoromethylpyrazolones derived nucleosides: Synthesis and antiviral evaluation.

Artigo em Inglês | MEDLINE | ID: mdl-30929566


Dengue (DENV) viral infection is a global public health problem that infrequently develops life threatening diseases such as dengue hemorrhagic fever (DFS) and dengue shock syndrome (DSS). Middle East respiratory syndrome coronavirus (MERS-CoV) is a highly pathogenic human corona virus with 38% fatality rate of infected patients. A series of 4-arylhydrazono-5-trifluoromethyl-pyrazolones, their ribofuranosyl, and 5'-deoxyribofuranosyl nucleosides were synthesized, geometry optimized using Density functional theory (DFT), and evaluated for their antiviral activity. 2-Nitrophenylhydrazonopyra-zolone derivative 5 showed significant activity against MERS-CoV (EC = 4.6 µM). The nucleoside analog 8 showed moderate activity against DENV-2 (EC = 10 µM), while the activity was abolished with the corresponding 5'-deoxyribonucleoside analogs. The identified hits in this study set this category of compounds for further future optimizations.

Febrile temperatures increase in vitro antibody affinity for malarial and dengue antigens.

PLoS Negl Trop Dis; 13(4): e0007239, 2019 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-30943193


Fever is a regulated increase of the body temperature resulting from both infectious and non-infectious causes. Fever is known to play a role in modulating immune responses to infection, but the potential of febrile temperatures in regulating antigen binding affinity to antibodies has not been explored. Here we investigated this process under in vitro conditions using Isothermal titration calorimetry and ELISA. We used selected malarial and dengue antigens against specific monoclonal antibodies, and observed a marked increase in the affinity of these antibody-antigen complexes at 40°C, compared to physiological (37°C) or pathophysiological temperatures (42°C). Induced thermal equilibration of the protein partners at these temperatures in vitro, prior to measurements, further increased their binding affinity. These results suggest another positive and adaptive role for fever in vivo, and highlight the favourable role of thermal priming in enhancing protein-protein affinity for samples with limited availability.

A predominant dengue virus-1 endemic strain and the vector competence of Aedes albopictus from Guangzhou City, China.

Acta Trop; 2019 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-30943381


INTRODUCTION: Dengue has been a serious public health burden and dengue virus-1 (DENV-1) is the predominant strain in Guangdong province, China. Differences exist in the transmission dynamics amongAedes albopictus and DENV in different geographical regions. However, little is known about the vector competence of indigenous Aedes albopictus for the predominant dengue strain in Guangdong province, China. METHODOLOGY: In this study, the field-derivedAedes albopictus collected from Guangzhou city, Guangdong province were infected with the predominant DENV endemic strain DENV-1 GZ201401 by feeding on serially diluted artificial infectious blood or infected suckling mice. DENV-infected mosquitoes were evaluated for viral load at five-time intervals in three tissues, the head, body and legs using reverse transcription-quantitative PCR (RT-qPCR). The vertical transmission of DENV in Ades albopictus was also analysed. Suckling mice were used to assess the transmission of DENV by Aedes albopictus. RESULTS: There was no difference in infection rates between mosquitoes infected by infected suckling mice or by artificial infectious blood. The proportion of DENV-1 positive mosquitoes increased over time after an infectious blood meal, but there was no difference in the positive rate beyond 7days after the blood meal. The positive rate of DENV-1 infected mosquitoes increased with the DENV titer in the blood meal. Most of the infections the infected mosquitoes were disseminated more than 7 days after imbibing the artificial infectious blood. The median infective doses (MID50) at 7,14,21 and 28 days after artificial infectious blood meal [7, 14, 21 and 28 days post-infection (dpi)] were 7.86 × 10 , 1.57 × 10 , 6.39 × 10 and 4.96 × 10 TCID (50% tissue culture infective dose)/ml, respectively. The mosquitoes can spread DENV-1 GZ201401 to hosts as early as 3 dpi. The vertical transmission of DENV-1 was documented with a cumulative rate of 17.61%. CONCLUSION: Our results demonstrated thatAedes albopictus mosquitoes are competent vectors for DENV-1, and are capable of maintaining autochthonous dengue outbreaks in Guangdong province, China, which may have been promoted by vertical transmission.
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