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1.
Rev Soc Bras Med Trop ; 54: e05192020, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33533817

RESUMO

INTRODUCTION: Dengue presents with a variable clinical course, ranging from mild illness to potentially fatal hemorrhage and shock. We aimed to evaluate the capabilities of various hematological parameters observed early in the course of illness for predicting the clinical outcomes of illness. METHODS: We retrospectively analyzed the records of children admitted in the pediatric inpatient services of the institute with dengue between 2017 and 2019. We determined the relationships between the hematological parameters observed during the first evaluation and the various clinical outcomes. RESULTS: We evaluated data from 613 patients (age range, 26 days to 17 years). Of these, 29.85% exhibited fever with warning signs, and 8.97% had severe dengue. Lower values of hemoglobin, platelet count, mean corpuscular volume, mean corpuscular hemoglobin concentration, and mean platelet volume, and higher values of total leukocyte count (TLC), hematocrit, and red cell distribution width variably correlated with numerous clinical outcomes-duration of hospital stay, development of complications, requirement of blood component transfusion, inotropic support, and mortality. Among the parameters, TLC ≥20,000/mL and initial platelet count ≤20,000/mL significantly associated with mortality, with odds ratios (95% confidence interval) of 11.81 (4.21-33.80) and 5.53 (1.90-16.09), respectively. CONCLUSIONS: Hematological parameters observed early during dengue infection may predict its clinical outcomes in infected children. Initial high TLC and low platelet count are potential predictors of fatal outcomes in the course of disease.


Assuntos
Dengue , Dengue Grave , Adulto , Criança , Dengue/diagnóstico , Hematócrito , Humanos , Índia/epidemiologia , Contagem de Leucócitos , Estudos Retrospectivos , Dengue Grave/diagnóstico
2.
BMJ Open ; 11(2): e043848, 2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33550260

RESUMO

OBJECTIVES: The study was focused on geographical mapping of dengue cases and also to identify the hotspots or high-risk areas of dengue in Delhi. DESIGN: A retrospective spatial-temporal (ecological) study. Descriptive analysis was used to know the distribution of dengue cases by age, sex, seasons and districts of Delhi. The spatiotemporal analysis was performed using inverse distance weighting and Getis-Ord Gi* statistic to know the geographical distribution and identify the hotspot areas. SETTINGS: All the confirmed and diagnosed dengue cases (IgM +ve or NS1 Antigen +ve ELISA) recorded by the Municipal Corporation of Delhi for the last 4 years (2015-2018) were collected with their local address. The location of all the dengue cases was geocoded using their address to prepare the spatiotemporal dengue database. PARTICIPANTS: Record of all the dengue cases (4179) reported for treatment in the hospitals during the past 4 years were extracted and included in the study. Data were not collected directly from dengue patients. RESULTS: Seasonal occurrence of dengue cases (4179) shows that the cases start emerging in July, peaked in September-October and declined in December. The proportions of dengue cases were recorded high among the males 57.3% compared with females 42.6%, and differences were also recorded in all the age groups with more cases in age groups <15 and 16-30 years. Mapping of the cases reflects the spatial heterogeneity in the geographical distribution. The geomapping of cases indicates the presence of a significantly high number of cases in West, Southwest, South and Southeast districts of Delhi. High-risk areas or hotspots were also identified in this region. CONCLUSION: Dengue occurrence shows significant association with age, sex and seasons. The spatial analysis identified the high-risk areas, which can aid health administrators to take necessary action for prevention and better disease management.

3.
Mem Inst Oswaldo Cruz ; 115: e200287, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33533869

RESUMO

BACKGROUND: The heat-labile nature of Dengue virus (DENV) in serum samples must be considered when applying routine diagnostic tests to avoid issues that could impact the accuracy of test results with direct implications for case management and disease reporting. OBJECTIVES: To check if pre-analytical variables, such as storage time and temperature, have an impact on the accuracy of the main routine diagnostic tests for dengue. METHODS: Virus isolation, reverse transcription real-time polymerase chain reaction (RT-PCR) and NS1 enzyme-linked immunosorbent assay (ELISA) were evaluated using 84 samples submitted to different pre-analytical conditions. FINDINGS: Sensitivity and negative predictive value were directly affected by sample storage conditions. RT-PCR and virus isolation showed greater dependence on well-conserved samples for an accurate diagnosis. Interestingly, even storage at -30ºC for a relatively short time (15 days) was not adequate for accurate results using virus isolation and RT-PCR tests. On the other hand, NS1 ELISA showed no significant reduction in positivity for aliquots tested under the same conditions as in the previous tests. MAIN CONCLUSIONS: Our results support the stability of the NS1 marker in ELISA diagnosis and indicate that the accuracy of routine tests such as virus isolation and RT-PCR is significantly affected by inadequate transport and storage conditions of serum samples.


Assuntos
Antígenos Virais/sangue , Vírus da Dengue/isolamento & purificação , Dengue/diagnóstico , Ensaio de Imunoadsorção Enzimática/métodos , Testes Imunológicos/métodos , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Proteínas não Estruturais Virais/imunologia , Anticorpos Antivirais/sangue , Antígenos Virais/imunologia , Dengue/sangue , Dengue/virologia , Vírus da Dengue/genética , Vírus da Dengue/imunologia , Humanos , Valor Preditivo dos Testes , Sensibilidade e Especificidade , Proteínas não Estruturais Virais/genética
4.
Mem Inst Oswaldo Cruz ; 115: e200313, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33533870

RESUMO

BACKGROUND: Aedes aegypti is the sole vector of urban arboviruses in French Guiana. Overtime, the species has been responsible for the transmission of viruses during yellow fever, dengue, chikungunya and Zika outbreaks. Decades of vector control have produced resistant populations to deltamethrin, the sole molecule available to control adult mosquitoes in this French Territory. OBJECTIVES: Our surveillance aimed to provide public health authorities with data on insecticide resistance in Ae. aegypti populations and other species of interest in French Guiana. Monitoring resistance to the insecticide used for vector control and to other molecule is a key component to develop an insecticide resistance management plan. METHODS: In 2009, we started to monitor resistance phenotypes to deltamethrin and target-site mechanisms in Ae. aegypti populations across the territory using the WHO impregnated paper test and allelic discrimination assay. FINDINGS: Eight years surveillance revealed well-installed resistance and the dramatic increase of alleles on the sodium voltage-gated gene, known to confer resistance to pyrethroids (PY). In addition, we observed that populations were resistant to malathion (organophosphorous, OP) and alpha-cypermethrin (PY). Some resistance was also detected to molecules from the carbamate family. Finally, those populations somehow recovered susceptibility against fenitrothion (OP). In addition, other species distributed in urban areas revealed to be also resistant to pyrethroids. CONCLUSION: The resistance level can jeopardize the efficiency of chemical adult control in absence of other alternatives and conducts to strongly rely on larval control measures to reduce mosquito burden. Vector control strategies need to evolve to maintain or regain efficacy during epidemics.


Assuntos
Aedes/efeitos dos fármacos , Insetos Vetores/genética , Resistência a Inseticidas/genética , Inseticidas/farmacologia , Mosquitos Vetores/efeitos dos fármacos , Piretrinas/farmacologia , Aedes/genética , Aedes/virologia , Animais , Guiana Francesa , Insetos Vetores/efeitos dos fármacos , Controle de Mosquitos/métodos , Mosquitos Vetores/virologia , Análise Espaço-Temporal
5.
J Neurovirol ; 2021 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-33528825

RESUMO

The association of dengue infection (DI) with atypical neurological manifestations was first reported in 1976. DENV-2 and DENV-3 serotypes are mostly related to neurological problems. DI has shown an overall risk of 21 autoimmune diseases, and 4% may develop neuromuscular complications. The pathogenetic mechanisms behind myasthenia gravis (MG) occurring during DI is thought to be linked to the neurotrophic effect of the infection. We report a unique case of DENV-1 infection presenting with bilateral ptosis and dysphagia in a previously healthy adult.

6.
Indian J Ophthalmol ; 69(3): 617-622, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33595487

RESUMO

Purpose: To describe a series of sight-threatening ocular and adnexal involvement associated with dengue hemorrhagic fever and their treatment options. Methods: Retrospective, interventional, non-comparative case series. Medical records of patients who presented with ocular symptoms attributed to dengue hemorrhagic fever were reviewed. Demography, presenting features, and treatment outcomes were recorded. Outcome measures assessed included globe salvage, vision salvage, and visual improvement. The outcome was deemed as favorable if vision salvage was possible and unfavorable if the vision was lost. Results: Twenty-nine eyes of 23 patients were included. Bilateral ocular involvement was seen in 6 (26%) patients. The mean age was 37.62 ± 18.68 years (range: 14 to 81 years). Coexistent diabetes mellitus and enteric fever were present in three patients. History of blood transfusion was present in nine (40%) and thrombocytopenia in eight (35%) patients at the time of presentation with ocular complaints. Presenting features included endophthalmitis in 11 (38%), panophthalmitis in 10 (35%), orbital cellulitis with panophthalmitis in four (14%), isolated corneal or scleral melt in three (10%), and orbital hemorrhage with panophthalmitis in one (3%) patient. Globe salvage was achieved in 21/29 eyes (72.4%), vision salvage in 6/29 eyes (20.68%), and improvement in visual acuity was noted in 5/29 eyes (17.24%). Logistic regression analysis revealed no significant effect of any clinical-microbiological factors on globe salvage, vision salvage, and visual improvement. However, visual improvement and globe salvage were possible in eyes that underwent early endoscopic vitrectomy. Conclusion: Dengue fever can present with sight-threatening ocular and adnexal inflammation resulting in endophthalmitis and panophthalmitis, orbital cellulitis, corneal and scleral melt, and orbital hemorrhage. Early vitrectomy may improve vision and globe salvage in cases with significant vitritis.

7.
Nat Commun ; 12(1): 1102, 2021 02 17.
Artigo em Inglês | MEDLINE | ID: mdl-33597521

RESUMO

The four-dengue virus (DENV) serotypes infect several hundred million people annually. For the greatest safety and efficacy, tetravalent DENV vaccines are designed to stimulate balanced protective immunity to all four serotypes. However, this has been difficult to achieve. Clinical trials with a leading vaccine demonstrated that unbalanced replication and immunodominance of one vaccine component over others can lead to low efficacy and vaccine enhanced severe disease. The Laboratory of Infectious Diseases at the National Institutes of Health has developed a live attenuated tetravalent DENV vaccine (TV003), which is currently being tested in phase 3 clinical trials. Here we report, our study to determine if TV003 stimulate balanced and serotype-specific (TS) neutralizing antibody (nAb) responses to each serotype. Serum samples from twenty-one dengue-naive individuals participated under study protocol CIR287 (ClinicalTrials.gov NCT02021968) are analyzed 6 months after vaccination. Most subjects (76%) develop TS nAbs to 3 or 4 DENV serotypes, indicating immunity is induced by each vaccine component. Vaccine-induced TS nAbs map to epitopes known to be targets of nAbs in people infected with wild type DENVs. Following challenge with a partially attenuated strain of DENV2, all 21 subjects are protected from the efficacy endpoints. However, some vaccinated individuals develop post challenge nAb boost, while others mount post-challenge antibody responses that are consistent with sterilizing immunity. TV003 vaccine induced DENV2 TS nAbs are associated with sterilizing immunity. Our results indicate that nAbs to TS epitopes on each serotype may be a better correlate than total levels of nAbs currently used for guiding DENV vaccine development.

8.
Int J Biometeorol ; 2021 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-33598765

RESUMO

Dengue transmission is climate-sensitive and permissive conditions regularly cause large outbreaks in Asia-Pacific area. As climate change progresses, extreme weather events such as heatwaves and unusually high rainfall are predicted more intense and frequent, but their impacts on dengue outbreaks remain unclear so far. This paper aimed to investigate the relationship between extreme weather events (i.e., heatwaves, extremely high rainfall and extremely high humidity) and dengue outbreaks in China. We obtained daily number of locally acquired dengue cases and weather factors for Guangzhou, China, for the period 2006-2015. The definition of dengue outbreaks was based on daily number of locally acquired cases above the threshold (i.e., mean + 2SD of daily distribution of dengue cases during peaking period). Heatwave was defined as ≥2 days with temperature ≥ 95th percentile, and extreme rainfall and humidity defined as daily values ≥95th percentile during 2006-2015. A generalized additive model was used to examine the associations between extreme weather events and dengue outbreaks. Results showed that all three extreme weather events were associated with increased risk of dengue outbreaks, with a risk increase of 115-251% around 6 weeks after heatwaves, 173-258% around 6-13 weeks after extremely high rainfall, and 572-587% around 6-13 weeks after extremely high humidity. Each extreme weather event also had good capacity in predicting dengue outbreaks, with the model's sensitivity, specificity, accuracy, and area under the receiver operating characteristics curve all exceeding 86%. This study found that heatwaves, extremely high rainfall, and extremely high humidity could act as potential drivers of dengue outbreaks.

9.
Transl Res ; 2021 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-33567345

RESUMO

Plasma leakage is a hallmark process in dengue viral (DENV) infection that occurs due to the loss of vascular integrity in endothelial cells. Endoglin (ENG) and Syndecan-1 (SDC-1) are released by activated endothelial cells; however, the complete dynamics of its expression at the gene and protein levels during the course of DENV infection remains unknown. In the present study, we quantified the mRNA and soluble protein levels of ENG and SDC-1 in dengue cases during febrile, defervescence, and convalescence stages in Dengue without Warning Sign (DWOW-15), Dengue with Warning Sign (DWW-22), and Severe Dengue cases (SD-10) compared to non-dengue Other Febrile Illness (OFI-10) and healthy control (HC-8). Respective protein and mRNA levels along with clinical characters were further analyzed for their efficacy in predicting disease outcomes using Support Vector Machine (SVM). We observed a steady and significant (P ≤ .01) increase in the levels of protein and mRNA of both the ENG and SDC-1 towards defervescence which is considered a critical phase in both severe and non-severe dengue cases. Importantly during the critical phase, the levels were significantly higher (P ≤ .001) in SD cases compared to DWW, DWOW, and OFI controls. However, at the time of admission (febrile), no such significant changes were observed within dengue, OFI, and healthy controls. SVM analysis revealed that the serum levels of ENG and SDC-1 along with other clinical symptoms could predict the disease severity with 100% accuracy. Based on the results we have proposed a mechanism on how ENG and SDC-1 could be involved in vascular dysfunction rather than just being a biomarker.

11.
Braz J Infect Dis ; : 101542, 2021 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-33587923

RESUMO

In response to the Zika epidemics in Brazil, the ZDC molecular assay (Bio-Manguinhos) was developed and registered at the Brazilian Regulatory Agency of Health Surveillance - ANVISA. The circulation of Zika (ZIKV) Dengue (DENV) and Chikungunya (CHIKV) viruses and their clinical similarities are challenges to correctly diagnose these viruses. The simultaneous detection of ZIKV, DENV and CHIKV is an important tool for diagnosis and surveillance. Here, we present the analytical and clinical performance evaluation of ZDC molecular assay (Bio-Manguinhos) at the public health laboratories three years after its registration at ANVISA. The clinical performance demonstrates the ZDC molecular assay (Bio-Manguinhos) has 100% sensitivity and 100% specificity to detect and discriminate ZIKV, CHIKV, and DENV from clinical plasma samples. The ZDC molecular assay (Bio-Manguinhos) results were highly reproducible and no cross-reactivity was seen during testing with a panel of other infectious agents. In conclusion, the ZDC molecular assay (Bio-Manguinhos) is an accurate and reliable tool to monitor Zika, dengue and chikungunya infections in countries like Brazil with simultaneous circulation of the three viruses.

12.
J Travel Med ; 2021 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-33590860

RESUMO

BACKGROUND: The case-fatality rate of dengue in travelers is low. Secondary dengue virus (DENV) infections are considered a risk factor for fatal outcome in endemic populations, however the impact of secondary infections on mortality in travelers has not been studied systematically. We performed a descriptive analysis of case reports of dengue fatalities in travelers. METHODS: We searched Medline for clinical case reports, using the free terms and MeSH headings: 'Dengue' OR 'Severe Dengue' AND 'Travel-Related Illness' OR 'travel' AND 'Mortality' OR 'Fatal Outcome'. We analyzed case reports of fatal dengue in returning travelers published from 1995 to 2020, with the objective to detail risk factors for dengue mortality in this population. We verified the authors' classifications of primary or secondary dengue infections; infections were considered as primary by absence of anti-DENV immunoglobulin (Ig)G or by IgM-to-IgG ratios greater than or equal to 1.8 in the first seven days post symptom onset. RESULTS: We identified nine detailed reports of dengue with fatal outcome among travelers from non-endemic countries. Eight fatalities were female. The median age was 32 years (range 21-63). Out of nine fatal cases, seven travelers had a primary DENV infection, one had a secondary infection, and in one this data was not reported. The infecting DENV serotypes were DENV-1 (n = 2), DENV-2 (n = 2) and DENV-3 (n = 3); DENV-1 or 2 (n = 1) and in one case the serotype could not be determined. CONCLUSIONS: Dengue-related deaths in travelers are rare. Most dengue cases in travelers are primary infections. Contrary to prevailing conceptions, we found that fatal outcomes of dengue in travelers from non-endemic countries were reported mainly with primary DENV infections. We alert health care providers that primary DENV infections are not always harmless and that in adult travelers from non-endemic countries, primary infections may contribute more to dengue-related mortality than secondary infections.

13.
Arch Virol ; 2021 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-33575893

RESUMO

Dengue virus (DV) is a mosquito-borne virus that is endemic to many tropical and subtropical areas. Recently, the annual incidence of DV infection has increased worldwide, including in Korea, due to global warming and increased global travel. We therefore sought to characterize the molecular and evolutionary features of DV-1 and DV-4 isolated from Korean overseas travelers. We used phylogenetic analysis based on the full coding region to classify isolates of DV-1 in Korea into genotype I (43251, KP406802), genotype IV (KP406803), and genotype V (KP406801). In addition, we found that strains of DV-4 belonged to genotype I (KP406806) and genotype II (43257). Evidence of positive selection in DV-1 strains was identified in the C, prM, NS2A, and NS5 proteins, whereas DV-4 showed positive selection only in the non-structural proteins NS2A, NS3, and NS5. The substitution rates per site per year were 5.58 × 10-4 and 6.72 × 10-4 for DV-1 and DV-4, respectively, and the time of the most recent common ancestor was determined using the Bayesian skyline coalescent method. In this study, the molecular, phylogenetic, and evolutionary characteristics of Korean DV-1 and DV-4 isolates were evaluated for the first time.

15.
Mem Inst Oswaldo Cruz ; 115: e200278, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33566939

RESUMO

BACKGROUND: The impact of arbovirus cocirculation in Brazil is unknown. Dengue virus (DENV) reinfection may result in more intense viraemia or immunopathology, leading to more severe disease. The Zika virus (ZIKV) epidemic in the Americas provided pathogenicity evidence that had not been previously observed in flavivirus infections. In contrast to other flaviviruses, electron microscopy studies have shown that ZIKV may replicate in viroplasm-like structures. Flaviviruses produce an ensemble of structurally different virions, collectively contributing to tissue tropism and virus dissemination. OBJECTIVES AND METHODS: In this work, the Aedes albopictus mosquito cell lineage (C6/36 cells) and kidney epithelial cells from African green monkeys (Vero cells) were infected with samples of the main circulating arboviruses in Brazil [DENV-1, DENV-2, DENV-3, DENV-4, ZIKV, Yellow Fever virus (YFV) and Chikungunya virus (CHIKV)], and ultrastructural studies by transmission electron microscopy were performed. FINDINGS: We observed that ZIKV, the DENV serotypes, YFV and CHIKV particles are spherical. ZIKV, DENV-1, -2, -3 and -4 presented diameters of 40-50 nm, and CHIKV presented approximate diameters of 50-60 nm. Viroplasm-like structures was observed in ZIKV replication cycle. MAIN CONCLUSIONS: The morphogenesis of these arboviruses is similar to what has been presented in previous studies. However, we understand that further studies are needed to investigate the relationship between viroplasm-like structures and ZIKV replication dynamics.


Assuntos
Arbovirus , Febre de Chikungunya , Dengue , Epidemias , Febre Amarela , Infecção por Zika virus , Zika virus , Animais , Brasil/epidemiologia , Febre de Chikungunya/epidemiologia , Chlorocebus aethiops , Dengue/epidemiologia , Células Vero , Infecção por Zika virus/epidemiologia
16.
Trop Doct ; : 49475520983643, 2021 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-33602052

RESUMO

Dengue fever is the most prevalent flavivirus infection in tropical and subtropical areas of the world. It is transmitted by the haematophagous mosquito Aedes aegypti, and it manifests clinically as classical dengue fever, dengue haemorrhagic fever and dengue shock syndrome. Rarely, dengue can be associated with neurophthalmic manifestations. We present the case of a 21-year-old woman, suffering from dengue with an isolated abducens nerve palsy.

17.
J Gen Virol ; 2021 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-33591246

RESUMO

Intra-host single nucleotide variants (iSNVs) have been increasingly used in genomic epidemiology to increase phylogenetic resolution and reconstruct fine-scale outbreak dynamics. These analyses are preferably done on sequence data from direct clinical samples, but in many cases due to low viral loads, there might not be enough genetic material for deep sequencing and iSNV determination. Isolation of the virus from clinical samples with low-passage number increases viral load, but few studies have investigated how dengue virus (DENV) culture isolation from a clinical sample impacts the consensus sequence and the intra-host virus population frequencies. In this study, we investigate consensus and iSNV frequency differences between DENV sequenced directly from clinical samples and their corresponding low-passage isolates. Twenty five DENV1 and DENV2 positive sera and their corresponding viral isolates (T. splendens inoculation and C6/36 passage) were obtained from a prospective cohort study in the Philippines. These were sequenced on MiSeq with minimum nucleotide depth of coverage of 500×, and iSNVs were detected using LoFreq. For both DENV1 and DENV2, we found a maximum of one consensus nucleotide difference between clinical sample and isolate. Interestingly, we found that iSNVs with frequencies ≥5 % were often preserved between the samples, and that the number of iSNV positions, and sample diversity, at this frequency cutoff did not differ significantly between the sample pairs (clinical sample and isolate) in either DENV1 or DENV2 data. Our results show that low-passage DENV isolate consensus genomes are largely representative of their direct sample parental viruses, and that low-passage isolates often mirror high frequency within-host variants from direct samples.

19.
Analyst ; 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33523052

RESUMO

The envelope glycoprotein domain III (EDIII) of dengue virus (DENV) has been recognised as the antigenic region responsible for receptor binding. In the present work, we have proposed a novel immunosensor constructed on a graphene-coated screen-printed carbon electrode (SPCE) using plant-derived EDIII as the probe antigen to target DENV IgG antibodies. The developed immunosensor demonstrated high sensitivity towards DENV IgG within a wide linear working range (125-2000 ng mL-1) under the optimised sensing conditions. The limit of detection was determined to be 22.5 ng mL-1. The immunosensor also showed high specificity towards DENV IgG, capable of differentiating DENV IgG from the antibodies of other infectious diseases including the similarly structured Zika virus (ZIKV). The ability of the immunosensor to detect dengue antibodies in serum samples was also verified by conducting tests on mouse serum samples. The proposed immunosensor was able to provide a binary (positive/negative) response towards the serum samples comparable to the conventional enzyme-linked immunosorbent assay (ELISA), indicating promising potential for realistic applications.

20.
PLoS Negl Trop Dis ; 15(2): e0009133, 2021 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-33591992

RESUMO

BACKGROUND: Our purpose was to provide a detailed clinical description, of symptoms and laboratory abnormalities, and temporality in patients with confirmed Zika and dengue infections, and other acute illnesses of unidentified origin (AIUO). METHODS/ PRINCIPAL FINDINGS: This was a two-year, multicenter, observational, prospective, cohort study. We collected data from patients meeting the Pan American Health Organization's modified case-definition criteria for probable Zika infection. We identified Zika, dengue chikungunya by RT-PCR in serum and urine. We compared characteristics between patients with confirmed Zika and dengue infections, Zika and AIUO, and Dengue and AIUO at baseline, Days 3,7,28 and 180 of follow-up. Most episodes (67%) consistent with the PAHO definition of probable Zika could not be confirmed as due to any flavivirus and classified as Acute Illnesses of Unidentified Origin (AIUO). Infections by Zika and dengue accounted for 8.4% and 16% of episodes. Dengue patients presented with fever, generalized non-macular rash, arthralgia, and petechiae more frequently than patients with Zika during the first 10 days of symptoms. Dengue patients presented with more laboratory abnormalities (lower neutrophils, lymphocytosis, thrombocytopenia and abnormal liver function tests), with thrombocytopenia lasting for 28 days. Zika patients had conjunctivitis, photophobia and localized macular rash more frequently than others. Few differences persisted longer than 10 days after symptoms initiation: conjunctivitis in Zika infections, and self-reported rash and petechia in dengue infections. CONCLUSIONS: Our study helps characterize the variety and duration of clinical features in patients with Zika, dengue and AIUO. The lack of diagnosis in most patients points to need for better diagnostics to assist clinicians in making specific etiologic diagnoses.

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