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Raman spectroscopy based differentiation of typhoid and dengue fever in infected human sera.

Spectrochim Acta A Mol Biomol Spectrosc; 206: 197-201, 2019 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-30114579


This study investigated the potential of Raman spectroscopy, to differentiate between two different types of human pathological conditions with some symptom similarity; typhoid and dengue. Raman spectra were recorded from 20 Salmonella Typhi infected and 22 dengue virus (DENV) infected sera samples using laser wavelength 785 nm. When Raman spectrum (540 to 1830 cm ) of serum samples was compared it showed significant variations. Twelve characteristic Raman bands at 562, 649, 716, 780, 838, 1099, 1144, 1156, 1260, 1386, 1556 and 1746 cm were recorded specifically in case of the typhoid infected samples, whereas four Raman bands at 756, 1218, 1672 and 1686 cm were found specifically in the DENV infected samples. For statistical differentiation principal component analysis (PCA) and linear discriminant analysis (LDA) was applied which successfully separated two sets of data. These disease specific Raman signatures may be labeled as biomarkers for identification as well as differential diagnosis of typhoid and dengue infection. Hence we propose that Raman spectroscopy has the potential to not only identify but also to differentiate between different pathological conditions, having some similar symptoms like high grade fever in this case.

An ensemble forecast model of dengue in Guangzhou, China using climate and social media surveillance data.

Sci Total Environ; 647: 752-762, 2019 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-30092532


BACKGROUND: China experienced an unprecedented outbreak of dengue in 2014, and the number of dengue cases reached the highest level over the past 25 years. There is a significant delay in the release of official case count data, and our ability to timely track the timing and magnitude of local outbreaks of dengue remains limited. MATERIAL AND METHODS: We developed an ensemble penalized regression algorithm (EPRA) for initializing near-real time forecasts of the dengue epidemic trajectory by integrating different penalties (LASSO, Ridge, Elastic Net, SCAD and MCP) with the techniques of iteratively sampling and model averaging. Multiple streams of near-real time data including dengue-related Baidu searches, Sina Weibo posts, and climatic conditions with historical dengue incidence were used. We compared the predictive power of the EPRA with the alternates, penalized regression models using single penalties, to retrospectively forecast weekly dengue incidence and detect outbreak occurrence defined using different cutoffs, during the periods of 2011-2016 in Guangzhou, south China. RESULTS: The EPRA showed the best or at least comparable performance for 1-, 2-week ahead out-of-sample and leave-one-out cross validation forecasts. The findings indicate that skillful near-real time forecasts of dengue and confidence in those predictions can be made. For detecting dengue outbreaks, the EPRA predicted periods of high incidence of dengue more accurately than the alternates. CONCLUSION: This study developed a statistically rigorous approach for near-real time forecast of dengue in China. The EPRA provides skillful forecasts and can be used as timely and complementary ways to assess dengue dynamics, which will help to design interventions to mitigate dengue transmission.

Correlation of dengue incidence and rainfall occurrence using wavelet transform for João Pessoa city.

Sci Total Environ; 647: 794-805, 2019 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-30096669


Dengue, a reemerging disease, is one of the most important viral diseases transmitted by mosquitoes. In this study, 55,680 cases of dengue between 2007 and 2015 were reported in Paraíba State, among which, 30% were reported in João Pessoa city, with peaks in 2015, 2011 and 2013. Weather is considered to be a key factor in the temporal and spatial distribution of vector-transmitted diseases. Thus, the relationship between rainfall occurrence and dengue incidences reported from 2007 to 2015 in João Pessoa city, Paraíba State, Brazil, was analyzed by means of wavelet transform, when a frequency analysis of both rainfall and dengue incidence signals was performed. To determine the relationship between rainfall and the incidence of dengue cases, a sample cross correlation function was performed to identify lags in the rainfall and temperature variables that might be useful predictors of dengue incidence. The total rainfall within 90 days presented the most significant association with the number of dengue cases, whereas temperature was not found to be a useful predictor. The correlation between rainfall and the occurrence of dengue cases showed that the number of cases increased in the first few months after the rainy season. Wavelet analysis showed that in addition to the annual frequency presented in both time series, the dengue time series also presented the 3-year frequency from 2010. Cross wavelet analysis revealed that such an annual frequency of both time series was in phase; however, after 2010, it was also possible to observe 45° up phase arrows, which indicated that rainfall in the present year led to an increased dengue incidence the following year. Thus, this approach to analyze surveillance data might be useful for developing public health policies for dengue prevention and control.

In situ removal of consensus dengue virus envelope protein domain III fused to hydrophobin in Pichia pastoris cultures.

Protein Expr Purif; 153: 131-137, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30240632


This work describes a novel strategy for the integrated expression and purification of recombinant proteins in Pichia pastoris cultures. Hydrophobins can be used as fusion tags, proteins fused to them alter their hydrophobicity and can be purified by aqueous two-phase systems (ATPS) based on non-ionic surfactants. Here, the consensus dengue virus envelope protein domain III fused to hydrophobin I of Trichoderma reesei was expressed in Pichia pastoris cultures and an in situ product removal by an ATPS using a non-ionic detergent, (Triton X-114) was performed. The protein was produced and purified directly from the yeast culture supernatant both efficiently and with no loss. The purified protein was properly immobilized by adsorption in solid phase and recognized by anti-dengue antibodies, showing its potential for the development of an indirect immunoassay for dengue virus.

Circulation of single serotype of Dengue Virus (DENV-3) in New Delhi, India during 2016: A change in the epidemiological trend.

J Infect Public Health; 2018 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-30274896


BACKGROUND: Dengue is a rapidly emerging arthropod borne viral infection affecting tropical and sub-tropical regions of the world. Dengue is an acute febrile illness but sometimes causes more fatal complications like dengue haemorrhagic fever (DHF) and dengue shock syndrome (DSS). Delhi, the capital of India has become hyper endemic for dengue virus because all the four serotypes are circulating here. METHODS: The present study describes the identification of dengue virus from clinical samples collected from the suspected dengue patients from New Delhi, India during 2016. The CprM region of Dengue virus genome was analyzed for phylogenetic, selection pressure and Shannon entropy analyses. RESULTS: The present study reports circulation of a single serotype (DENV-3) in New Delhi, during 2016. The phylogenetic analysis revealed that Indian subcontinent (genotype III) of DENV-3 was circulating in Delhi during this period. Neutral selection pressure in the analyzed region revealed relatively conserved nature of this part of the Dengue virus genome. Amino acid at 31 was positively selected and had high entropy value suggesting probability of variation at this position. CONCLUSIONS: The changing trend in circulation of dengue virus serotypes necessitates the continuous epidemiological surveillance for the dengue outbreaks in this region.

Impact of a Nonfatal Dengue Episode on Disability-Adjusted Life Years: A Systematic Analysis.

Am J Trop Med Hyg; 2018 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-30277202


As dengue causes about 4,000 symptomatic nonfatal episodes for every dengue death globally, quantitative disability assessments are critical to assess the burden of dengue and the cost-effectiveness of dengue control interventions. This systematic analysis of disability or quality of life lost from a symptomatic nonfatal dengue episode combined a systematic literature review, statistical modeling, and probabilistic sensitivity analyses. We conceptualized a dengue episode as having two phases: acute and persistent symptoms. Our estimates for the acute phase, consisting of onset and recovery periods and defined as the first 20 days (0.054 year), were based on literature review. We searched PubMed, POPLINE, EconLit, Google Scholar, scientific conferences, and other sources, for "dengue" plus "quality of life" or related terms. From 4,322 initial entries, six met our criteria (original studies with empirical data). The median disability-adjusted life year (DALY) burden for the acute phase was 0.011 (95% certainty interval [CI]: 0.006-0.015) for ambulatory episodes, 0.015 (CI: 0.010-0.020) for hospitalized episodes, and 0.012 (CI: 0.006-0.019) overall. Using literature reviews about persistent dengue, we estimated that 34% of episodes experienced persistent symptoms with a median duration of symptoms of 0.087 (CI: 0.040-0.359) year, which resulted in median DALYs of 0.019 (CI: 0.008-0.082). Thus, the overall median DALY burden was 0.031 (CI: 0.017-0.092) for ambulatory episodes, 0.035 (CI: 0.024-0.096) for hospitalized episodes, and 0.032 (CI: 0.018-0.093) overall. Our dengue-specific burden of a dengue episode was 2.1 times the 2013 Global Burden of Disease estimate. These literature-based estimates provide an empirical summary for policy and cost-effectiveness analyses.

Molecular Investigation of Dengue virus serotype 2 Circulation in Kassala State, Sudan.

Jpn J Infect Dis; 2018 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-30270247


The tropical nature of Sudan promotes the spread of mosquito-transmitted diseases such as dengue virus (DENV) infection. The current knowledge about the geographical distribution of DENV serotypes and genotypes in Sudan is limited. In this study, molecular techniques (Reverse Transcriptase -PCR and sequencing) followed by phylogenetic analysis were used to characterize DENV isolated from blood samples of suspected dengue patients admitted to Kassala Hospital, Kassala state, Sudan, in 2016/ 2017. We identified DENV infection in 4 patients by RT-PCR. Phylogenetic analysis demonstrated that the isolated virus sequences belong to the Cosmopolitan genotype of DENV serotype 2. This is the first study to confirm the presence of DENV serotype 2 in Kassala state, Sudan. This study urges the need for a wider investigation of the DENV serotypes composition and estimating their contribution to the ongoing transmission.

Need for guidelines for the combined management of pregnancy and dengue: a retrospective study from an Indian tertiary care maternity hospital.

Trop Doct; : 49475518800638, 2018 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-30270767


The incidence of dengue has risen in India in recent years. Evidence suggests that dengue in pregnancy may be associated with adverse maternal and fetal outcomes. The aim of our study was to analyse outcomes in pregnant women with confirmed dengue infection who had the benefit of close monitoring and intensive management at a tertiary maternity facility. We reviewed hospital data of 44 (0.11%) such women at Fernandez Hospital, a tertiary maternity unit, during the five-year period from 2011 to 2016. Maternal and fetal variables were collected from case sheets. Dengue haemorrhagic fever was seen in 15.9% and dengue shock syndrome in one fatal case (2.2%). Thrombocytopenia was seen in 31 cases (70.4%) and 14 (31.81%) received platelets transfusions. Fetal outcomes in our series were favourable, except for one stillbirth, with 45.4% preterm deliveries and 15.9% small for gestational age babies. Dengue in pregnancy is definitely associated with maternal and fetal morbidity and mortality. A high index of suspicion of dengue is required in pregnant women with pyrexia and thrombocytopenia.

First Report on Detection of Dengue Virus in the Donor Cornea.

Cornea; 2018 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-30272614


BACKGROUND: Dengue fever is the most prevalent form of flavivirus infection in humans. We have investigated whether corneoscleral tissue of the donor affected by dengue virus (DENV) harbors the virus. PURPOSE: To identify the risk for viral transmission through corneal transplants in areas where DENV circulates. METHODS: Excised corneoscleral tissue from a cadaver with a history of viral hemorrhagic fever was analyzed using reverse transcriptase-polymerase chain reaction for the presence of DENV and chikungunya virus (CHIV). RESULTS: DENV was detected in RNA extracted from the donor corneoscleral rim. Further genotyping of the viral isolate from the virus-infected cell harvest revealed DENV type 3 as the causative agent. CHIV was not detected. CONCLUSIONS: The data presented in this study recommend the implementation of polymerase chain reaction for detection of DENV and CHIV to analyze excised corneoscleral tissue of a donor with viral hemorrhagic fever.

A prospective matched study on symptomatic dengue in pregnancy.

PLoS One; 13(10): e0202005, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30281605


Dengue fever is an increasing problem worldwide, but consequences during pregnancy remain unclear. Much of the available literature suffers from methodological biases that compromise the validity of clinical recommendations. We conducted a matched cohort study during an epidemic in French Guiana to compare events and pregnancy outcomes between two paired groups of pregnant women: women having presented with symptomatic dengue during pregnancy (n = 73) and women having had neither fever nor dengue during pregnancy (n = 219). Women in each arm were matched by place of follow up, gestation weeks at inclusion, and place of residence. Dengue infection was considered to be confirmed if viral RNA, N S1 antigen, the seroconversion of IgM antibodies or the presence of IgM was detected in collected samples. According to the 2009 WHO classification, 27% of the women with symptomatic dengue had at least one clinical or biological warning sign. These complications occurred after the 28th week of gestation in 55% of cases. The medical history, socioeconomic status and demographic characteristics were included in multivariate analysis. Exposure to dengue during pregnancy was not significantly associated with prematurity, small for gestational age infants, hypertension or emergency caesarian section. Maternal dengue with warning signs was a risk factor for peripartum hemorrhage with adjusted relative risk = 8.6(95% CI = 1.2-62). There was a near significant association between dengue and in utero death (p = 0.09). This prospective comparative study underlined the importance of taking into account potential confounders between exposure to dengue and the occurrence of obstetrical events. It also confirms the need for increased vigilance for pregnant women with dengue, particularly for women who present with severe dengue.

Detection and serotyping of dengue viruses in febrile patients consulting at the New-Bell District Hospital in Douala, Cameroon.

PLoS One; 13(10): e0204143, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30281633


Arboviruses are a major public health problem worldwide and are predominantly present in intertropical areas. Chikungunya, dengue and zika viruses have been implicated in recent epidemics in Asia, America and Africa. In Cameroon, data on these viruses are fragmentary. The purpose of this study was to determine the frequency of detection of these three viruses in febrile patients in Douala, Cameroon. A cross-sectional and descriptive study was conducted from March to April 2017 at the New-Bell District Hospital in Douala. Blood samples were collected from febrile patients and tested for malaria infections using Rapid Diagnostic test. Plasma harvested was later analyzed for the presence of chikungunya, dengue and zika viruses by a Trioplex real-time RT-PCR at Centre Pasteur of Cameroon. A total of 114 participants were included, of which 63.2% were females, reflecting a sex ratio (female/male) of 1.7. The median age was 26 years, range [0.25-81]. Eight (7%) of the 114 participants were infected with Dengue virus (DENV) among which 5 were identified as serotype 1. No cases of infection by either Zika virus or Chikungunya virus were detected. Three cases of dengue-malaria co-infection (13%) were recorded. No association was found between socio-demographic factors and dengue infection. The phylogenetic analysis of the partial envelope E gene showed that all the five DENV serotype 1 samples belonged to subtype V, similarly to strains from West African countries, particularly those from Nigeria, Senegal and Côte d'Ivoire. This study showed the circulation of DENV serotype 1 in febrile patients and raises the alarm for the establishment of a sustained surveillance system to detect cases and prevent potential outbreaks in Cameroon. The existence of dengue-malaria co-infections suggests that surveillance of arboviruses should not be limited to febrile, non-malarial cases.

Different aspects of platelet evaluation in dengue: measurement of circulating mediators, ability to interact with the virus, the degree of activation and quantification of intraplatelet protein content.

Virus Res; 2018 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-30282001


Platelets play a role in hemostasis, coagulation, angiogenesis, inflammation and immune response is one of the most affected cells in dengue. Here we describe some aspects of platelets by observing their specific circulating mediators, the ability to interact with the virus and morphological consequences of this interaction, activation markers and intraplatelet protein contents in dengue. We conducted this study using dengue-patients as well as healthy donors. Immunoenzymatic assay, flow cytometry, transmission electron microscopy and intraplatelet proteins expression assays were carried out. Briefly, we found an increase in sCD62 L, NO or TBX2 ratio in platelet count, mostly in patients with the worse clinical outcome. After in vitro DENV infection or during natural infection, platelets underwent morphological alteration with increased expression of platelet activation markers, particularly in natural infections. Analysis of intraplatelet protein contents revealed different angiogenic and inflammatory profiles, maintaining or not extracellular matrix integrity between DF and DFWS patients. Thus, platelets are frequently affected by dengue, either by altering their own functionality, as "carrier" of the virus, or as an antiviral and mediator-secreting effector cell. Thus, strategies aimed at recovering platelet amounts in dengue seem to be essential for a better clinical outcome of the patients.

Relationship between local presence and density of Aedes aegypti eggs with dengue cases: A spatial analysis approach.

Trop Med Int Health; 2018 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-30282110


OBJECTIVES: To analyze the relationship between the occurrence of dengue and ovitrap positivity and dengue egg density in two Amazonas municipalities (Brazil) in 2016. METHODS: We performed a case-control study using secondary data from the dengue fever surveillance system. Ovitraps distributed regularly in the urban area of two cities were used to monitor the presence of the vector. The relationship between egg positivity, egg density, and the location of dengue cases was evaluated using two approaches as follows: (i) based on the result of the nearest neighbor ovitrap and (ii) based on the results of the set of ovitraps within the influence area of 300 meters from the location of each case and control. RESULTS: During the study period, 229 confirmed cases of dengue fever were reported in Tabatinga and 89 cases in Itacoatira. In this study, we found that the positivity of ovitraps was related to the occurrence of dengue in Tabatinga and Itacoatiara. An association between egg density of Ae. aegypti and dengue occurrence was also observed in Itacoatiara. The temporal lags for ovitrap positivity measurements were predominantly 15 or 30 days. A dengue association for egg density for a 15-day time lag was detected for one of the case-control approaches. CONCLUSIONS: The location of dengue cases is related to ovitrap egg positivity, while a less evident possible association may exist for egg density. This indicates that these traps could be used to improve vector control actions. This article is protected by copyright. All rights reserved.

Comparison between the traditional (1997) and revised (2009) WHO classifications of dengue disease: a retrospective study of 30,670 patients.

Trop Med Int Health; 2018 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-30282115


OBJECTIVE: To compare WHO's traditional (1997) and revised (2009) guidelines for dengue classification, using a large sample of patients of all ages with varying clinical conditions from a dengue endemic area in an inland city in Brazil. METHODS: We compared 30,670 laboratory-confirmed dengue cases (1998-2012) from a dengue-endemic area using both dengue classification guidelines. Stereotype ordinal logistic regressions were used to analyze the association between patients' demographics and signs and symptoms related to dengue infection severity, as defined in the 1997 and 2009 guidelines. We then compared the degree of agreement of both guidelines for included patients. RESULTS: We found poor agreement between dengue severity and signs and symptoms defined by both guidelines (Cramer's V test <0.2). Hypotensive shock was the exception for both classifications and presented dependence (Z=56.42; p<0.001, and Z= 55.24; p <0.001) and an excellent degree of agreement (Cramers's V=1; p<0.001, and Cramers's V=0.97; p<0.001) for WHO 1997 and 2009, respectively. We found substantial agreement between both guidelines (Kendall tau-b=0.79; p<0.001). CONCLUSIONS: These results inform the debate about the WHO guidelines, particularly concerning clinical value, lack of study comparability, and ways in which future guideline improvements could support the clinical management of dengue. Based on our results, we believe caution should be taken when using WHO guidelines to assess severity, to improve clinical management of dengue. This article is protected by copyright. All rights reserved.

Raman spectroscopic and fractal analysis of blood samples of dengue fever patients.

Biomed Mater Eng; 2018 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-30282334


BACKGROUND: The limitations of the existing techniques for the early detection of dengue fever necessitate the development of a powerful optical technique. OBJECTIVE: The present work is a study of Raman spectral modifications of blood on dengue infection and thereby to develop a spectroscopic method for its early detection. The images of the samples are subjected to fractal analysis to find the variation of fractal dimensions on dengue infection. METHODS: Correlation of platelet counts of dengue infected blood with Raman spectrum modification and fractal dimension. The effect of lowering of blood platelet count due to dengue infection is found to show some interesting changes in the spectrum. RESULTS: The full width at half maximum (FWHM) of the two bands in the region 950-1200 cm-1 increase with the decrease of blood platelet count. The increase in fractal dimension gives an indication of the decrease of platelet count and hence the dengue infection. CONCLUSIONS: Raman spectrum and fractal analysis can effectively be used as potential techniques for the early detection of dengue infection.

Development of standard clinical endpoints for use in dengue interventional trials.

PLoS Negl Trop Dis; 12(10): e0006497, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30286085


Dengue is a major public health problem worldwide. Although several drug candidates have been evaluated in randomized controlled trials, none has been effective and at present, early recognition of severe dengue and timely supportive care are used to reduce mortality. While the first dengue vaccine was recently licensed, and several other candidates are in late stage clinical trials, future decisions regarding widespread deployment of vaccines and/or therapeutics will require evidence of product safety, efficacy and effectiveness. Standard, quantifiable clinical endpoints are needed to ensure reproducibility and comparability of research findings. To address this need, we established a working group of dengue researchers and public health specialists to develop standardized endpoints and work towards consensus opinion on those endpoints. After discussion at two working group meetings and presentations at international conferences, a Delphi methodology-based query was used to finalize and operationalize the clinical endpoints. Participants were asked to select the best endpoints from proposed definitions or offer revised/new definitions, and to indicate whether contributing items should be designated as optional or required. After the third round of inquiry, 70% or greater agreement was reached on moderate and severe plasma leakage, moderate and severe bleeding, acute hepatitis and acute liver failure, and moderate and severe neurologic disease. There was less agreement regarding moderate and severe thrombocytopenia and moderate and severe myocarditis. Notably, 68% of participants agreed that a 50,000 to 20,000 mm3 platelet range be used to define moderate thrombocytopenia; however, they remained divided on whether a rapid decreasing trend or one platelet count should be case defining. While at least 70% agreement was reached on most endpoints, the process identified areas for further evaluation and standardization within the context of ongoing clinical studies. These endpoints can be used to harmonize data collection and improve comparability between dengue clinical trials.

Dengue illness index-A tool to characterize the subjective dengue illness experience.

PLoS Negl Trop Dis; 12(10): e0006593, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30286086


Dengue virus infections are a major cause of febrile illness that significantly affects individual and societal productivity and drives up health care costs principally in the developing world. Two dengue vaccine candidates are in advanced clinical efficacy trials in Latin America and Asia, and another has been licensed in more than fifteen countries but its uptake has been limited. Despite these advances, standardized metrics for comparability of protective efficacy between dengue vaccines remain poorly defined. The Dengue Illness Index (DII) is a tool that we developed thru refinement of previous similar iterations in an attempt to improve and standardize the measurement of vaccine and drug efficacy in reducing moderate dengue illness. The tool is designed to capture an individual's overall disease experience based on how the totality of their symptoms impacts their general wellness and daily functionality. We applied the DII to a diary card, the Dengue Illness Card (DIC), which was examined and further developed by a working group. The card was then refined with feedback garnered from a Delphi methodology-based query that addressed the adequacy and applicability of the tool in clinical dengue research. There was overall agreement that the tool would generate useful data and provide an alternative perspective to the assessment of drug or vaccine candidates, which in the case of vaccines, are assessed by their reduction in any virologically confirmed dengue of any severity with a focus on the more severe. The DIC needs to be evaluated in the field in the context of vaccine or drug trials, prospective cohort studies, or during experimental human infection studies. Here, we present the final DIC resulting from the Delphi process and offer its further development or use to the dengue research community.

Inter- and intra-host sequence diversity reveal the emergence of viral variants during an overwintering epidemic caused by dengue virus serotype 2 in southern Taiwan.

PLoS Negl Trop Dis; 12(10): e0006827, 2018 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-30286095


Purifying selection during dengue viral infection has been suggested as the driving force of viral evolution and the higher complexity of the intra-host quasi-species is thought to offer an adaptive advantage for arboviruses as they cycle between arthropod and vertebrate hosts. However, very few studies have been performed to investigate the viral genetic changes within (intra-host) and between (inter-host) humans in a spatio-temporal scale. Viruses of different serotypes from various countries imported to Taiwan cause annual outbreaks. During 2001-2003, two consecutive outbreaks were caused by dengue virus serotype 2 (DENV-2) and resulted in a larger-scale epidemic with more severe dengue cases in the following year. Phylogenetic analyses showed that the viruses from both events were similar and related to the 2001 DENV-2 isolate from the Philippines. We comprehensively analyzed viral sequences from representative dengue patients and identified three consensus genetic variants, group Ia, Ib and II, with different spatio-temporal population dynamics. The phylodynamic analysis suggested group Ib variants, characterized by lower genetic diversity, transmission rate, and intra-host variant numbers, might play the role of maintenance variants. The residential locations among the patients infected by group Ib variants were in the outer rim of case clusters throughout the 2001-2003 period whereas group Ia and II variants were located in the centers of case clusters, suggesting that group Ib viruses might serve as "sheltered overwintering" variants in an undefined ecological niche. Further deep sequencing of the viral envelope (E) gene directly from individual patient serum samples confirmed the emergence of variants belonging to three quasi-species (group Ia, Ib, and II) and the ancestral role of the viral variants in the latter phase of the 2001 outbreak contributed to the later, larger-scale epidemic beginning in 2002. These findings enhanced our understanding of increasing epidemic severity over time in the same epidemic area. It also highlights the importance of combining phylodynamic and deep sequencing analysis as surveillance tools for detecting dynamic changes in viral variants, particularly searching for and monitoring any specific viral subpopulation. Such subpopulations might have selection advantages in both fitness and transmissibility leading to increased epidemic severity.

Safety Follow-up of a Dengue Vaccine When Administered Concomitantly with a Yellow Fever Vaccine in Healthy Toddlers in Colombia.

Pediatr Infect Dis J; 37(11): 1190-1191, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30308599


This was a safety follow-up study conducted in 382 toddlers in Colombia who had last received dengue vaccine (CYD-TDV) 2 years before. A review of local municipal epidemiologic reports for dengue cases was also conducted for ~28 months postimmunization. One case of clinical dengue was reported; it was neither considered as severe nor related to the study vaccine.
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