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1.
Einstein (Sao Paulo) ; 18: eAO5078, 2020.
Artigo em Inglês, Português | MEDLINE | ID: mdl-31859787

RESUMO

OBJECTIVE: To evaluate the performance of indirect immunofluorescence for serological diagnosis of dengue virus in a population with high prevalence of arboviruses. METHODS: Two-hundred serum samples from patients with clinical suspicion of dengue fever were tested by immunoenzymatic and indirect immunofluorescence assay BIOCHIP® mosaic. Specificity, sensitivity and Kappa coefficient were calculated. Discordant samples were tested by polymerase chain reaction for confirmation. RESULTS: Of the 200 samples, 20% were positive and 80% negative for anti-dengue virus IgM antibodies in the immunoenzymatic test. Of the 40 positives, 25% were negative in indirect immunofluorescence. Of these ten discordant results, only 20% were also negative in the polymerase chain reaction (PCR). Of the 160 negatives in the immunoenzymatic test, 5% were positive in indirect immunofluorescence. Of these nine discordant results, 33% were positive in the PCR. The Kappa coefficient was 0.7 (0.572-0.829). Sensitivity and specificity of indirect immunofluorescence were respectively 75% and 94%. For anti-dengue virus IgG antibodies, of the 200 samples, 15.5% were positive and 84.5% were negative in the immunoenzymatic test. Of the 31 positives, 12.9% were negative in indirect immunofluorescence. Of these four discordant results, 25% were negative in the PCR. Of the 169 negatives, 8% were positive in indirect immunofluorescence. Of these 14 discordant results, 64% were also positive in the PCR. The Kappa coefficient was 0.695 (0.563-0.83). Sensitivity and specificity of indirect immunofluorescence were 87.1% and 91.7%, respectively. CONCLUSION: For diagnosis of acute infection, the immunoenzymatic test is enough, and the use of additional methods is not warranted. Replacing the immunoenzymatic test by indirect immunofluorescence would compromise the sensitivity for IgM. However, indirect immunofluorescence can distinguish three arboviruses simultaneously, an advantage during concomitant epidemics.


Assuntos
Dengue/diagnóstico , Ensaio de Imunoadsorção Enzimática/métodos , Técnica Indireta de Fluorescência para Anticorpo/métodos , Anticorpos Antivirais/imunologia , Arbovirus/isolamento & purificação , Brasil , Dengue/imunologia , Vírus da Dengue/isolamento & purificação , Ensaio de Imunoadsorção Enzimática/normas , Técnica Indireta de Fluorescência para Anticorpo/normas , Humanos , Imunoglobulina G/imunologia , Imunoglobulina M/imunologia , Reação em Cadeia da Polimerase , Padrões de Referência , Sensibilidade e Especificidade , Testes Sorológicos/métodos , Testes Sorológicos/normas
2.
PLoS Negl Trop Dis ; 13(12): e0007817, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31805088

RESUMO

BACKGROUND: Hepatic dysfunction and coagulopathy are common in acute dengue illness. We analyzed the trajectories of the above parameters in the survivors and fatal patients in the outbreak in Tainan, 2015. METHODS: A retrospective study was conducted using data from a tertiary hospital between January and December 2015. Multilevel modeling (MLM) was used to identify the changes in aminotransferase (AST), alanine aminotransferase (ALT), activated partial thromboplastin time (aPTT), and platelet counts from Day 0 to Day 7 of the onset of dengue infection. The machine-learning algorithm was used by purity measure assumption to calculate the accuracy of serum transaminases and coagulation variables to discriminate between the fatal and survival groups. RESULTS: There were 4,069 dengue patients, of which 0.9% died in one week after illness onset (i.e., early mortality). Case fatality rate was the highest for those aged ≥70 years. Both AST and ALT values of the fatal group were significantly higher than those of the survivor group from Day 3 (AST median, 624 U/L vs. 60 U/L, p < 0.001; ALT median, 116 U/L vs. 29 U/L, p = 0.01) of illness onset and peaked on Day 6 (AST median, 9805 U/L vs. 90 U/L, p < 0.001; ALT median, 1504 U/L vs. 49 U/L, p < 0.001). AST ≥ 203 U/L, ALT ≥ 55 U/L, AST2/ALT criteria ≥337.35, or AST/platelet count ratio index (APRI) ≥ 19.18 on Day 3 of dengue infection had a high true positive rate, 90%, 78%, 100%, or 100%, respectively, of early mortality. The platelet counts of the fatal group declined significantly than those of the survivor group since Day 3 of illness onset (median, 19 x103/µl vs. 91 x103/µl, p < 0.01), and aPTT values of the fatal group significantly prolonged longer since Day 5 (median, 68.7 seconds vs. 40.1 seconds, p < 0.001). CONCLUSIONS: AST, ALT, and platelet counts should be monitored closely from Day 0 to Day 3 of dengue infection, and aPTT be followed up on Day 5 of infection to identify the individuals at risk for early mortality.


Assuntos
Testes de Coagulação Sanguínea/métodos , Dengue/diagnóstico , Dengue/mortalidade , Testes de Função Hepática/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Criança , Pré-Escolar , Dengue/epidemiologia , Dengue/patologia , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Tempo de Tromboplastina Parcial , Contagem de Plaquetas , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida , Taiwan/epidemiologia , Centros de Atenção Terciária , Adulto Jovem
3.
BMC Infect Dis ; 19(1): 970, 2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31722678

RESUMO

BACKGROUND: Acute febrile illness (AFI) is characterized by malaise, myalgia and a raised temperature that is a nonspecific manifestation of infectious diseases in the tropics. The lack of appropriate diagnostics for the evaluation of AFI leads to increased morbidity and mortality in resource-limited settings, specifically low-income countries like India. The review aimed to identify the number, type and quality of diagnostics used for AFI evaluation during passive case detection at health care centres in South India. METHODS: A scoping review of peer-reviewed English language original research articles published between 1946-July 2018 from four databases was undertaken to assess the type and number of diagnostics used in AFI evaluation in South India. Results were stratified according to types of pathogen-specific tests used in AFI management. RESULTS: The review included a total of 40 studies, all conducted in tertiary care centres (80% in private settings). The studies demonstrated the use of 5-22 tests per patient for the evaluation of AFI. Among 25 studies evaluating possible causes of AFI, 96% tested for malaria followed by 80% for dengue, 72% for scrub typhus, 68% for typhoid and 60% for leptospirosis identifying these as commonly suspected causes of AFI. 54% studies diagnosed malaria with smear microscopy while others diagnosed dengue, scrub typhus, typhoid and leptospirosis using antibody or antigen detection assays. 39% studies used the Weil-Felix test (WFT) for scrub typhus diagnosis and 82% studies used the Widal test for diagnosing typhoid. CONCLUSIONS: The review demonstrated the use of five or more pathogen-specific tests in evaluating AFI as well as described the widespread use of suboptimal tests like the WFT and Widal in fever evaluation. It identified the need for the development of better-quality tests for aetiological diagnosis and improved standardised testing guidelines for AFI.


Assuntos
Doenças Transmissíveis/diagnóstico , Anticorpos/sangue , Antígenos/análise , Dengue/diagnóstico , Humanos , Índia , Leptospirose/diagnóstico , Malária/diagnóstico , Tifo por Ácaros/diagnóstico , Centros de Atenção Terciária
4.
PLoS Negl Trop Dis ; 13(10): e0007785, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31634352

RESUMO

BACKGROUND: Dengue virus (DENV) infection is a major cause of acute febrile illness in Indonesia. Diagnostic inaccuracy may occur due to its varied and non-specific presentation. Characterization of DENV epidemiology, clinical presentation, and virology will facilitate appropriate clinical management and public health policy. METHODOLOGY/PRINCIPAL FINDINGS: A multicenter observational cohort study was conducted in Indonesia to assess causes of acute fever requiring hospitalization. Clinical information and specimens were collected at enrollment, 14-28 days, and 3 months from 1,486 children and adults. Total of 468 (31.9%) cases of DENV infection were confirmed by reference laboratory assays. Of these, 414 (88.5%) were accurately diagnosed and 54 had been misdiagnosed as another infection by sites. One hundred initially suspected dengue cases were finally classified as 'non-dengue'; other pathogens were identified in 58 of those cases. Mortality of DENV infection was low (0.6%). Prior DENV exposure was found in 92.3% of subjects >12 years. DENV circulated year-round in all cities, with higher incidence from January to March. DENV-3 and DENV-1 were the predominant serotypes. This study identified DENV-1 with TS119(C→T) substitution in the serotyping primer annealing site, leading to failure of serotype determination. CONCLUSIONS/SIGNIFICANCE: DENV is a common etiology of acute febrile illness requiring hospitalization in Indonesia. Diagnostic accuracy at clinical sites merits optimization since misdiagnosis of DENV infection and over-estimation of dengue can negatively impact management and outcomes. Mutation at the annealing site of the serotyping primer may confound diagnosis. Clinicians should consider following diagnostic algorithms that include DENV confirmatory testing. Policy-makers should prioritize development of laboratory capacity for diagnosis of DENV.


Assuntos
Vírus da Dengue/genética , Dengue/diagnóstico , Dengue/epidemiologia , Dengue/virologia , Mutação , Adolescente , Adulto , Algoritmos , Criança , Pré-Escolar , Técnicas de Laboratório Clínico/métodos , Estudos de Coortes , Dengue/fisiopatologia , Vírus da Dengue/classificação , Feminino , Febre , Genótipo , Mapeamento Geográfico , Política de Saúde , Hospitalização , Humanos , Incidência , Indonésia/epidemiologia , Masculino , Filogenia , Saúde Pública , Sorogrupo , Sorotipagem , Adulto Jovem
5.
Afr Health Sci ; 19(2): 2000-2007, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31656483

RESUMO

Background: In the last five decades, dengue has emerged as one of the most important infectious diseases, following a 30-fold increase in global incidence throughout tropical and sub-tropical regions of the world. The actual numbers of dengue cases are under-reported and many cases are misclassified. Objectives: This article describes the epidemiology, pathophysiology, clinical features and management of dengue. It also explores the implications of infection with this flavivirus for Nigeria, and similar countries. Methods: The literature search for publications on dengue in West Africa was performed using PubMed, African Journals Online (AJOL), Google Scholar, Web of Science, databases and grey literature to identify all published papers regarding the topic. A snowballing strategy was adopted to identify additional publications. Results: Recent reports suggest that dengue is a growing public health problem in Nigeria, the magnitude of which needs to be more clearly defined. Nigeria, the most populous country in Africa has an abundance of the Aedes aegypti mosquito which is known to transmit dengue, Zika, as well as chikungunya (CHIKV) and West Nile viruses. Conclusion: This article provides practical suggestions for strengthening the dengue virus control programme in Nigeria. The Nigerian health system shares similarities with health systems in many other sub-Saharan countries. Therefore, the practical suggestions provided at the end of this review are likely to be applicable to many other African countries.


Assuntos
Aedes/virologia , Vírus da Dengue/isolamento & purificação , Dengue/prevenção & controle , Controle de Mosquitos , Mosquitos Vetores/virologia , Animais , Dengue/diagnóstico , Humanos , Nigéria
6.
PLoS Negl Trop Dis ; 13(10): e0007773, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31658252

RESUMO

In 2012, the U.S. Defense Threat Reduction Agency Joint Science and Technology Office initiated a program to develop novel point-of-need diagnostic devices for surveillance of emerging infectious diseases including dengue, malaria, plague, and melioidosis. Prior to distribution of devices to observe their correct use among community members in Iquitos, Peru, and Phnom Penh, Cambodia, research was conducted to: 1) assess acceptability of use, including the motivation to use a rapid diagnostic test (RDT) before or instead of seeking care at a health facility, 2) explore comprehension of RDT use instructions, and 3) examine possible strategies for large scale RDT distribution and use at each site. In February 2014, 9 focus group discussions (FGD) with community members and 5 FGD with health professionals were conducted in Iquitos, and 9 FGD with community members and 9 in-depth interviews with health professionals in Phnom Penh. In both places, participants agreed to use the device themselves (involving finger prick) or could identify someone who could do so in their home or neighborhood. The main incentive to RDT use in both sites was the ability for device results to be used for care facilitation (post confirmatory tests), specifically reduced wait times to be seen or obtain a diagnosis. Comprehension of RDT use instructions was assessed in Iquitos by asking some participants to apply the device to research team members; after watching a short video, most steps were done correctly. In Phnom Penh, participants were asked to describe each step after reading the instructions; they struggled with comprehension. Health professionals' main concerns in both sites were their community's ability to accurately use the test, handle complicated instructions, and safety (i.e., disposal of lancets). Health system structure and ability to use home diagnostic devices varied in the two disease endemic sites, with substantial challenges in each, suggesting the need for different strategies for RDT large scale community use, and illustrating the value of formative research before deployment of novel technologies.


Assuntos
Testes Diagnósticos de Rotina/métodos , Testes Diagnósticos de Rotina/normas , Pessoal de Saúde/educação , Adolescente , Adulto , Camboja , Dengue/diagnóstico , Educação/métodos , Feminino , Grupos Focais , Instalações de Saúde , Conhecimentos, Atitudes e Prática em Saúde , Pesquisa sobre Serviços de Saúde , Humanos , Malária/diagnóstico , Masculino , Melioidose/diagnóstico , Pessoa de Meia-Idade , Aceitação pelo Paciente de Cuidados de Saúde , Peru , Peste/diagnóstico , Manejo de Espécimes/métodos , Adulto Jovem
7.
Pak J Pharm Sci ; 32(4): 1545-1554, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31608873

RESUMO

Malaria, dengue and chikungunya are the most rampant mosquito-borne infections predominantly in Pakistan. They pose a serious threat and cause a havoc for the victims owing to the life threatening signs and symptoms marked with elevated morbidity and mortality rate. It seems hard to discriminate due to common indications, consequently, deserves appropriate diagnosis prior elevated toll of death. Present article encompasses depth insights about their prevalence, diagnosis and clinical manifestation if erupt in the pandemic. However, host-vector-host cycle is the root cause of transmission and diverse mosquito species confer dissimilar infections. Indeed these infections are seasonal but other factors like flood, open irrigation channels, immense agricultural land, rich fauna and water reservoirs can't be overlooked. Dire need was felt to acknowledge and aware the public about local transmission, vector control, entomologic, research resources, diagnosis and advancement in healthcare system to alleviate them absolutely in future.


Assuntos
Febre de Chikungunya/diagnóstico , Febre de Chikungunya/epidemiologia , Dengue/diagnóstico , Dengue/epidemiologia , Malária/tratamento farmacológico , Malária/epidemiologia , Antimaláricos/uso terapêutico , Febre de Chikungunya/tratamento farmacológico , Dengue/complicações , Dengue/tratamento farmacológico , Humanos , Malária/diagnóstico , Paquistão/epidemiologia , Prevalência , Fatores Socioeconômicos
8.
Arch Virol ; 164(12): 2895-2908, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31531742

RESUMO

Dengue virus (DENV) is a mosquito-borne arbovirus that causes febrile illness and can lead to a potentially lethal disease. The mechanism of disease pathogenesis is not completely understood, and there are currently no vaccines or therapeutic drugs available to protect against all four serotypes of DENV. Although many reasons have been suggested for the development of the disease, dengue studies have shown that, during DENV infection, there is an imbalance between oxidants and antioxidants that disrupts homeostasis. An increase in reactive oxygen species (ROS) levels triggers the sudden release of cytokines, which can lead to plasma leakage and other severe symptoms. In the present review, we give an overview of the oxidative stress response and its effect on the progression of dengue disease. We also discuss the role of oxidative-stress-associated molecules in disease prognostic and therapeutics.


Assuntos
Vírus da Dengue/patogenicidade , Dengue/diagnóstico , Espécies Reativas de Oxigênio/metabolismo , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Citocinas , Dengue/tratamento farmacológico , Dengue/imunologia , Dengue/metabolismo , Vírus da Dengue/efeitos dos fármacos , Vírus da Dengue/imunologia , Homeostase , Humanos , Estresse Oxidativo/efeitos dos fármacos , Prognóstico , Sorogrupo , Virulência/efeitos dos fármacos
9.
Curr Opin Ophthalmol ; 30(6): 500-505, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31503074

RESUMO

PURPOSE OF REVIEW: There are an increasing number of publications related to dengue ophthalmic manifestations and multimodality imaging related to dengue. This review summarizes the current literature, describe ocular manifestations, current using of ocular imaging/investigations, and management of ocular dengue. RECENT FINDINGS: Ocular manifestations of dengue can be present in many stages of dengue fever including after the resolution of systemic disease. Most cases of ocular dengue will exhibit an improvement in vision spontaneously over time. Multimodal imaging such as optical coherence tomography, optical coherence tomography angiography, near-infrared imaging, and microperimetry plays an important role in the diagnosis, follow-up, quantitative measure, and help to understand the disease progression. SUMMARY: Dengue fever can lead to a variety of ocular manifestations. The mechanisms underlying dengue-related ocular complications remain unclear. Immune-mediated mechanisms and direct viral invasion are thought to play an important role. Ophthalmologists should carefully assess patients with dengue-related ophthalmic disease because some patients may have poor visual acuity and exhibit refractoriness to treatment. Treatment with systemic corticosteroids may benefit those patients with poor presenting visual acuity, progressive ocular symptoms, and lesions involving the optic nerve and/or threatening the macula.


Assuntos
Dengue/diagnóstico , Infecções Oculares Virais/diagnóstico , Transtornos da Visão/diagnóstico , Dengue/virologia , Infecções Oculares Virais/virologia , Angiofluoresceinografia , Humanos , Imagem Multimodal , Espectrofotometria Infravermelho , Tomografia de Coerência Óptica/métodos , Transtornos da Visão/virologia , Testes de Campo Visual
10.
Rev Soc Bras Med Trop ; 52: e20190304, 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31508787

RESUMO

INTRODUCTION: Human parvovirus B19 (B19V) is a common pathogen, which on infection causes variety of clinical conditions from benign self-limiting exanthematous disease and other similar pathologies to fetal death. METHODS: We collected 341 serum samples between the first and fourth day after the onset of symptoms from all patients suspected of dengue fever who were attended at Regional Hospital of Tefé. Initially, patients were screened for malaria by blood smear test and negative samples were sent to Fundação de Medicina Tropical Doutor Heitor Vieira Dourado (FMT-HVD) situated in Manaus (AM) for dengue testing using semi-nested multiplex PCR. Further, we investigated 44 malaria and dengue-negative samples of children for B19V DNA by nested-PCR. Positive samples were analyzed by BLAST against entire public non-redundant nucleotide database and genotyped by phylogenetic analyses using neighbor-joining clustering method. RESULTS: Eight samples (18.2%) were found to be PCR positive. Fever, headache, ocular pain, and/or muscle pain were reported as the most frequent symptoms by the patients and none were diagnosed with rash at the time of sample collection. Phylogenetic analysis of major capsid protein 2 (VP2) and VP3 coding region showed high similarity with B19V genotype 1. CONCLUSIONS: Our results reveal the spread of B19V genotype 1 in Tefé. Moreover, our results emphasize the significance of laboratorial differential diagnosis using molecular techniques in patients with acute febrile, and thereby aid the health surveillance system in improving patient care even in the remote areas of Amazon.


Assuntos
DNA Viral/sangue , Dengue/diagnóstico , Infecções por Parvoviridae/diagnóstico , Infecções por Parvoviridae/virologia , Parvovirus B19 Humano/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Brasil , Criança , Pré-Escolar , Feminino , Genótipo , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Filogenia , Reação em Cadeia da Polimerase , Adulto Jovem
11.
BMC Public Health ; 19(1): 1148, 2019 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-31522680

RESUMO

BACKGROUND: A clear understanding of the epidemiology of malaria and dengue co-infection is essential for informed decisions on appropriate control strategies for dengue and malaria. This systematic review synthesized evidence on the relationship of malaria and dengue co-infection and related it to alterations in platelet, hemoglobin, hematocrit, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) levels when compared to malaria mono-infection. METHODS: A systematic review in accordance with PRISMA guidelines was conducted. All published articles available in PubMed and Web of Science (ISI) databases before October 21, 2017 were recruited. All epidemiological studies except case reports on the prevalence or incidence of malaria and dengue co-infection among patients visiting hospitals with febrile illness were included. Studies that involved conference abstracts, protocols, systematic reviews, only mono-dengue or mono-malaria infections, and only animal or in vitro studies were excluded after screening the titles, abstracts, and body texts. Studies were additionally excluded after full text review when they lacked epidemiologic data on malaria and dengue co-infection. Two reviewers independently screened, reviewed, and assessed all the studies. Cochrane Q (Chi-square) and Moran's I2 were used to assess heterogeneity, and the funnel plot was used to examine publication bias. The summary odds ratio (OR) and 95% confidence intervals (CI) were estimated using a fixed-effects model. Thirteen cross-sectional and two retrospective studies were eligible to be included in the systematic review and meta-analysis. RESULTS: Out of the 2269 citations screened, 15 articles were eligible to be included in the systematic review and meta-analysis. The 15 studies involved 13,798 (10,373 cases with malaria and 3425 with dengue) patients in 9 countries. Thirteen studies compared the incidence and odds of Plasmodium sp. infection, five studies compared the odds of mean platelet, three studies compared Plasmodium parasite density, and four studies compared the odds of hemoglobin, hematocrit, AST, and ALT levels among co-infected groups and single-malaria-infected groups. CONCLUSIONS: This study showed that dengue and malaria co-infection was associated with decreased odds of malaria infection, malaria parasitemia, AST, and ALT levels when compared to malaria mono-infection. However, malaria and dengue co-infection was associated with increased odds of platelet and hemoglobin levels when compared to malaria mono-infection.


Assuntos
Coinfecção , Dengue , Malária , Animais , Coinfecção/epidemiologia , Estudos Transversais , Dengue/diagnóstico , Dengue/epidemiologia , Hematócrito , Hospitais , Humanos , Laboratórios , Malária/diagnóstico , Malária/epidemiologia , Razão de Chances , Parasitemia , Prevalência , Estudos Retrospectivos
12.
PLoS Negl Trop Dis ; 13(9): e0007747, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31539394

RESUMO

BACKGROUND: Zika virus (ZIKV) and Dengue virus (DENV) are often co-endemic. The high protein-sequence homology of flaviviruses renders IgG induced by and directed against them highly cross-reactive against their antigen(s), as observed on a large set of sera, leading to poorly reliable sero-diagnosis. METHODS: We selected Domain III of the ZIKV Envelope (ZEDIII) sequence, which is virus specific. This recombinant domain was expressed and purified for the specific detection of ZEDIII-induced IgG by ELISA from ZIKV-RT-PCR-positive, ZIKV-IgM-positive, flavivirus-positive but ZIKV-negative, or flavivirus-negative sera. We also assessed the reactivity of ZEDIII-specific human antibodies against EDIII of DENV serotype 4 (D4EDIII) as a specific control. Sera from ZEDIII-immunized mice were also tested. RESULTS: Cross-reactivity of IgG from 5,600 sera against total inactivated DENV or ZIKV was high (71.0% [69.1; 72.2]), whereas the specificity and sensitivity calculated using a representative cohort (242 sera) reached 90% [84.0; 95.8] and 92% [84.5; 99.5], respectively, using a ZEDIII-based ELISA. Moreover, purified human IgG against D2EDIII or D4EDIII did not bind to ZEDIII and we observed no D4EDIII reactivity with ZIKV-induced mouse polyclonal IgGs. CONCLUSIONS: We developed a ZEDIII-based ELISA that can discriminate between past or current DENV and ZIKV infections, allowing the detection of a serological scar from other flaviviruses. This could be used to confirm exposure of pregnant women or to follow the spread of an endemic disease.


Assuntos
Ensaio de Imunoadsorção Enzimática/métodos , Infecção por Zika virus/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Anticorpos Antivirais/sangue , Criança , Pré-Escolar , Dengue/diagnóstico , Dengue/imunologia , Vírus da Dengue/imunologia , Feminino , Humanos , Imunoglobulina G , Lactente , Masculino , Camundongos , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Zika virus/imunologia , Infecção por Zika virus/imunologia , Infecção por Zika virus/virologia
13.
Comput Math Methods Med ; 2019: 7307803, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31485259

RESUMO

Early diagnosis of dengue continues to be a concern for public health in countries with a high incidence of this disease. In this work, we compared two machine learning techniques: artificial neural networks (ANN) and support vector machines (SVM) as assistance tools for medical diagnosis. The performance of classification models was evaluated in a real dataset of patients with a previous diagnosis of dengue extracted from the public health system of Paraguay during the period 2012-2016. The ANN multilayer perceptron achieved better results with an average of 96% accuracy, 96% sensitivity, and 97% specificity, with low variation in thirty different partitions of the dataset. In comparison, SVM polynomial obtained results above 90% for accuracy, sensitivity, and specificity.


Assuntos
Dengue/diagnóstico , Adulto , Bases de Dados Factuais/estatística & dados numéricos , Dengue/epidemiologia , Diagnóstico Precoce , Feminino , Humanos , Masculino , Conceitos Matemáticos , Modelos Biológicos , Paraguai/epidemiologia , Máquina de Vetores de Suporte , Adulto Jovem
14.
PLoS Negl Trop Dis ; 13(9): e0007047, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31487279

RESUMO

BACKGROUND: Pathogens causing acute fever, with the exception of malaria, remain largely unidentified in sub-Saharan Africa, given the local unavailability of diagnostic tests and the broad differential diagnosis. METHODOLOGY: We conducted a cross-sectional study including outpatient acute undifferentiated fever in both children and adults, between November 2015 and June 2016 in Kinshasa, Democratic Republic of Congo. Serological and molecular diagnostic tests for selected arboviral infections were performed on blood, including PCR, NS1-RDT, ELISA and IFA for acute, and ELISA and IFA for past infections. RESULTS: Investigation among 342 patients, aged 2 to 68 years (mean age of 21 years), with acute undifferentiated fever (having no clear focus of infection) revealed 19 (8.1%) acute dengue-caused by DENV-1 and/or DENV-2 -and 2 (0.9%) acute chikungunya infections. Furthermore, 30.2% and 26.4% of participants had been infected in the past with dengue and chikungunya, respectively. We found no evidence of acute Zika nor yellow fever virus infections. 45.3% of patients tested positive on malaria Rapid Diagnostic Test, 87.7% received antimalarial treatment and 64.3% received antibacterial treatment. DISCUSSION: Chikungunya outbreaks have been reported in the study area in the past, so the high seroprevalence is not surprising. However, scarce evidence exists on dengue transmission in Kinshasa and based on our data, circulation is more important than previously reported. Furthermore, our study shows that the prescription of antibiotics, both antibacterial and antimalarial drugs, is rampant. Studies like this one, elucidating the causes of acute fever, may lead to a more considerate and rigorous use of antibiotics. This will not only stem the ever-increasing problem of antimicrobial resistance, but will-ultimately and hopefully-improve the clinical care of outpatients in low-resource settings. TRIAL REGISTRATION: ClinicalTrials.gov NCT02656862.


Assuntos
Febre de Chikungunya/diagnóstico , Dengue/diagnóstico , Febre/diagnóstico , Adolescente , Adulto , Idoso , Febre de Chikungunya/epidemiologia , Febre de Chikungunya/virologia , Vírus Chikungunya/genética , Vírus Chikungunya/isolamento & purificação , Vírus Chikungunya/fisiologia , Criança , Pré-Escolar , Estudos Transversais , República Democrática do Congo/epidemiologia , Dengue/epidemiologia , Dengue/virologia , Vírus da Dengue/genética , Vírus da Dengue/isolamento & purificação , Vírus da Dengue/fisiologia , Feminino , Febre/epidemiologia , Febre/virologia , Humanos , Malária/diagnóstico , Malária/epidemiologia , Masculino , Pessoa de Meia-Idade , Pacientes Ambulatoriais/estatística & dados numéricos , Adulto Jovem
15.
BMC Infect Dis ; 19(1): 680, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31370795

RESUMO

BACKGROUND: A major challenge in dengue management in resource limited settings is the confirmation of diagnosis. Clinical features of dengue often overlap with other infections and molecular diagnostic tools are not readily accessible to clinicians at hospitals. In addition, the prediction of plasma leakage in dengue is also difficult. Hematocrit level and ultrasound scans (combined with clinical parameters) are helpful to detect plasma leakage once it has happened, not before. METHODS: Colombo Dengue Study (CDS) is a prospective cohort study of clinically suspected adult dengue patients recruited from the National hospital of Sri Lanka (within the first 3 days of fever) that aimed to a) identify clinical and basic laboratory test parameters to differentiate dengue from non-dengue fever, b) evaluate the comparative efficacy of loop-mediated isothermal amplification (LAMP) for dengue diagnosis (vs. NS1 antigen test and RT-qPCR) and c) identify early associations that are predictive of plasma leakage or severe dengue. The basic laboratory tests considered here included hematological parameters, serum biochemistry and inflammatory markers. RESULTS: Only 70% of clinically suspected patients were confirmed as having dengue by either the NS1 antigen test or RT-qPCR. On a Bayesian latent class model which assumes no "gold standard", LAMP performed equally or better than RT-qPCR and NS1 antigen test respectively. When confirmed dengue patients were compared with others, the earlier group had significantly lower lymphocyte counts and higher aspartate aminotransferase levels (AST) within the first 3 days of fever. Confirmed dengue patients with plasma leakage had a lower mean age and a higher median baseline AST level compared to those without plasma leakage (p < 0.05). CONCLUSION: Clinical suspicion overestimates the true number of dengue patients. RT-LAMP is a potentially useful low-cost diagnostic tool for dengue diagnosis. Confirmed dengue patients had significantly higher AST levels and lower lymphocyte counts in early disease compared to others. In confirmed dengue patients, younger age and a higher AST level in early infection were associated with subsequent plasma leakage.


Assuntos
Aspartato Aminotransferases/sangue , Técnicas de Amplificação de Ácido Nucleico/métodos , Dengue Grave/diagnóstico , Dengue Grave/etiologia , Adulto , Teorema de Bayes , Biomarcadores/sangue , Estudos de Coortes , Dengue/diagnóstico , Vírus da Dengue/genética , Feminino , Febre/virologia , Humanos , Testes Imunológicos , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Reação em Cadeia da Polimerase em Tempo Real/métodos , Medição de Risco , Sensibilidade e Especificidade , Dengue Grave/sangue , Sri Lanka
16.
Virol J ; 16(1): 102, 2019 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-31416485

RESUMO

BACKGROUND: Dengue virus (DENV) infection is one of the biggest challenges for human health in the world. In addition, a secondary DENV infection sometimes causes dengue hemorrhagic fever (DHF), which frequently leads to death. For this reason, accurate diagnosis record management is useful for prediction of DHF. Therefore, the demand for DENV rapid diagnosis tests (RDTs) is increasing because these tests are easy and rapid to use. However, commercially available RDTs often show low sensitivity for DENV and cross-reactivity against other flaviviruses, especially Zika virus (ZIKV). METHODS: We developed two types of novel DENV non-structural protein 1 (NS1) detection RDTs, designated TKK-1st and TKK-2nd kits. Specificities of the monoclonal antibodies (MAbs) used in these kits were confirmed by enzyme-linked immuno-sorbent assay (ELISA), dot blot, and western blot using recombinant NS1 proteins and synthetic peptides. For evaluation of sensitivity, specificity, and cross-reactivity of the novel DENV NS1 RDTs, we first used cultured DENV and other flaviviruses, ZIKV and Japanese encephalitis virus (JEV). We then used clinical specimens obtained in Bangladesh in 2017 for further evaluation of kit sensitivity and specificity in comparison with commercially available RDTs. In addition, RNA extracted from sera were used for viral genome sequencing and genotyping. RESULTS: Epitopes of three out of four MAbs used in the two novel RDTs were located in amino acid positions 100 to 122 in the NS1 protein, a region that shows low levels of homology with other flaviviruses. Our new kits showed high levels of sensitivity against various serotypes and genotypes of DENV and exhibited high levels of specificity without cross-reactivity against ZIKV and JEV. In clinical specimens, our RDTs showed sensitivities of 96.0% (145/151, TKK-1st kit) and 96.7% (146/151, TKK-2nd kit), and specificities of 98.0% (98/100, TKK-1st kit and TKK-2nd kit). On the other hand, in the case of the commercially available SD Bioline RDT, sensitivity was 83.4% (126/151) and specificity was 99.0% (99/100) against the same clinical specimens. CONCLUSIONS: Our novel DENV NS1-targeting RDTs demonstrated high levels of sensitivity and lacked cross-reactivity against ZIKV and JEV compared with commercially available RDTs.


Assuntos
Vírus da Dengue/isolamento & purificação , Dengue/diagnóstico , Kit de Reagentes para Diagnóstico/normas , Proteínas não Estruturais Virais/genética , Anticorpos Monoclonais/imunologia , Anticorpos Antivirais/sangue , Antígenos Virais/imunologia , Bangladesh , Western Blotting , Reações Cruzadas , Ensaio de Imunoadsorção Enzimática , Humanos , Immunoblotting , Limite de Detecção , Proteínas Recombinantes/genética , Sensibilidade e Especificidade , Zika virus
17.
Mikrobiyol Bul ; 53(3): 348-353, 2019 Jul.
Artigo em Turco | MEDLINE | ID: mdl-31414637

RESUMO

The frequency of travel-related infections in the world has increased due to the easily and widespread use of travel facilities in the 21st century. Vector-borne diseases are an important part of infectious diseases. Dengue fever is one of the travel-related infections that has been reported increasingly in recent years through the development of diagnostic methods. The aim of this report was to present two Dengue fever cases originating from travel. There was a story of mosquito bite during a trip to Sri Lanka travel in our first case. The patient was 30 years old and maculopapular rash appeared on the fifth day of contact. Three days after the onset of the rash, she has admitted to our clinic, complaining with fever and chills. Increased leukopenia and muscle enzymes were detected in the laboratory analysis. Real-time reverse transcriptase polimerase chain reaction (RT-PCR) was positive in the serum sample. The patient was followed up with supportive care and discharged by improvement. The second case, a 24-year-old male, had a story of mosquito bite during his trip to Malaysia. After the patient complained of fever, chills, fever, nausea, vomiting and muscle pain, the Dengue virus (DENV) NS1 antigen test performed in this country was found to be positive. In the second case, there was no maculopapular rash and laboratory analysis showed an increase in leukopenia, thrombocytopenia and muscle enzymes. RT-PCR positivity was detected in the serum sample. The patient was followed up with supportive treatment and discharged with cure. DENV infections are caused by DENV which is common in the tropical areas of the world. There are four DENV-1, DENV-2, DENV-3 and DENV-4 serotypes. DENV infections can present different clinical manifestations such as asymptomatic disease, viral syndrome, Dengue haemorrhagic fever, and Dengue shock syndrome. Dengue fever is often accompanied by arthritis, maculopapular rash and high fever. Our cases were defined as Dengue fever according to this definition. In the diagnosis of the disease, it is necessary first to be suspicious of the disease and the travel history must be questioned. In the definitive diagnosis, virus isolation, antigen, nucleic acid detection and serological tests are used. The virus can be isolated from blood, serum, urine and tissues. In the first five days after beginning of the symptoms associated with DENV infections, serum RT-PCR and Dengue NS1 antigen test may be positive.


Assuntos
Vírus da Dengue , Dengue , Doença Relacionada a Viagens , Adulto , Dengue/complicações , Dengue/diagnóstico , Dengue/patologia , Dengue/virologia , Vírus da Dengue/classificação , Exantema/etiologia , Feminino , Humanos , Malásia , Masculino , Sri Lanka , Resultado do Tratamento , Adulto Jovem
18.
PLoS Negl Trop Dis ; 13(8): e0007649, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31442225

RESUMO

The explosive spread of Zika virus (ZIKV) and associated complications in flavivirus-endemic regions underscore the need for sensitive and specific serodiagnostic tests to distinguish ZIKV, dengue virus (DENV) and other flavivirus infections. Compared with traditional envelope protein-based assays, several nonstructural protein 1 (NS1)-based assays showed improved specificity, however, none can detect and discriminate three flaviviruses in a single assay. Moreover, secondary DENV infection and ZIKV infection with previous DENV infection, both common in endemic regions, cannot be discriminated. In this study, we developed a high-throughput and multiplex IgG microsphere immunoassay (MIA) using the NS1 proteins of DENV1-DENV4, ZIKV and West Nile virus (WNV) to test samples from reverse-transcription-polymerase-chain reaction-confirmed cases, including primary DENV1, DENV2, DENV3, WNV and ZIKV infections, secondary DENV infection, and ZIKV infection with previous DENV infection. Combination of four DENV NS1 IgG MIAs revealed a sensitivity of 94.3% and specificity of 97.2% to detect DENV infection. The ZIKV and WNV NS1 IgG MIAs had a sensitivity/specificity of 100%/87.9% and 86.1%/78.4%, respectively. A positive correlation was found between the readouts of enzyme-linked immunosorbent assay and MIA for different NS1 tested. Based on the ratio of relative median fluorescence intensity of ZIKV NS1 to DENV1 NS1, the IgG MIA can distinguish ZIKV infection with previous DENV infection and secondary DENV infection with a sensitivity of 88.9-90.0% and specificity of 91.7-100.0%. The multiplex and high-throughput assay could be applied to serodiagnosis and serosurveillance of DENV, ZIKV and WNV infections in endemic regions.


Assuntos
Anticorpos Antivirais/sangue , Dengue/diagnóstico , Imunoensaio/métodos , Microesferas , Testes Sorológicos/métodos , Febre do Nilo Ocidental/diagnóstico , Infecção por Zika virus/diagnóstico , Ensaios de Triagem em Larga Escala , Humanos , Imunoglobulina G/sangue , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologia , Sensibilidade e Especificidade , Proteínas não Estruturais Virais/genética , Proteínas não Estruturais Virais/imunologia
19.
PLoS Negl Trop Dis ; 13(8): e0007144, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31430283

RESUMO

The objective of this study was to assess the validity of the new dengue classification proposed by the World Health Organization (WHO) in 2009 and to develop pragmatic guidelines for case triage and management. This retrospective study involved 357 laboratory-confirmed cases of dengue infection diagnosed at King Abdulaziz University Hospital, Jeddah, Saudi Arabia over a 4-year period from 2014 to 2017. The sensitivity of the new classification for identifying severe cases was limited (65%) but higher than the old one (30%). It had a higher sensitivity for identifying patients who needed advanced healthcare compared to the old one (72% versus 32%, respectively). We propose adding decompensation of chronic diseases and thrombocytopenia-related bleeding to the category of severe dengue in the new classification. This modification improves sensitivity from 72% to 98% for identifying patients who need advanced healthcare without altering specificity (97%). It also improves sensitivity in predicting severe outcomes from 32% to 88%. In conclusion, the new classification had a low sensitivity for identifying patients needing advanced care and for predicting morbidity and mortality. We propose to include decompensation of chronic diseases and thrombocytopenia-related bleeding to the category of severe dengue in the new classification to improve the sensitivity of predicting cases requiring advanced care.


Assuntos
Dengue/classificação , Dengue/diagnóstico , Organização Mundial da Saúde , Adolescente , Adulto , Criança , Pré-Escolar , Doença Crônica , Medicina Clínica/métodos , Medicina Clínica/normas , Dengue/fisiopatologia , Feminino , Hemorragia , Hospitais Universitários , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Arábia Saudita , Sensibilidade e Especificidade , Dengue Grave/classificação , Dengue Grave/diagnóstico , Índice de Gravidade de Doença , Trombocitopenia , Adulto Jovem
20.
Rev Inst Med Trop Sao Paulo ; 61: e40, 2019 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-31432989

RESUMO

Several arboviruses have emerged and/or re-emerged in North, Central and South-American countries. Viruses from some regions of Africa and Asia, such as the Zika and Chikungunya virus have been introduced in new continents causing major public health problems. The aim of this study was to investigate the presence of RNA from Zika, Dengue and Chikungunya viruses in symptomatic patients from Rondonia, where the epidemiological profile is still little known, by one-step real-time RT-PCR. The main clinical signs and symtoms were fever (51.2%), headache (78%), chills (6.1%), pruritus (12.2%), exanthema (20.1%), arthralgia (35.3%), myalgia (26.8%) and retro-orbital pain (19.5%). Serum from 164 symptomatic patients were collected and tested for RNA of Zika, Dengue types 1 to 4 and Chikungunya viruses, in addition to antibodies against Dengue NS1 antigen. Direct microscopy for Malaria was also performed. Only ZIKV RNA was detected in 4.3% of the patients, and in the remaining 95.7% of the patients RNA for Zika, Dengue and Chikungunya viruses were not detected. This finding is intriguing as the region has been endemic for Dengue for a long time and more recently for Chikungunya virus as well. The results indicated that medical and molecular parameters obtained were suitable to describe the first report of symptomatic Zika infections in this region. Furthermore, the low rate of detection, compared to clinical signs and symptoms as the solely diagnosis criteria, suggests that molecular assays for detection of viruses or other pathogens that cause similar symptoms should be used and the corresponding diseases could be included in the compulsory notification list.


Assuntos
Febre de Chikungunya/epidemiologia , Vírus Chikungunya/genética , Vírus da Dengue/genética , Dengue/epidemiologia , Infecção por Zika virus/epidemiologia , Zika virus/genética , Brasil/epidemiologia , Febre de Chikungunya/diagnóstico , Dengue/diagnóstico , Humanos , Vírus de RNA/genética , Reação em Cadeia da Polimerase em Tempo Real , Infecção por Zika virus/diagnóstico
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