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1.
BMC Infect Dis ; 20(1): 835, 2020 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-33176708

RESUMO

BACKGROUND: The spatial distribution and burden of dengue in sub-Saharan Africa remains highly uncertain, despite high levels of ecological suitability. The goal of this study was to describe the epidemiology of dengue among a cohort of febrile children presenting to outpatient facilities located in areas of western Uganda with differing levels of urbanicity and malaria transmission intensity. METHODS: Eligible children were first screened for malaria using rapid diagnostic tests. Children with a negative malaria result were tested for dengue using a combination NS1/IgM/IgG rapid test (SD Bioline Dengue Duo). Confirmatory testing by RT-PCR was performed in a subset of participants. Antigen-capture ELISA was performed to estimate seroprevalence. RESULTS: Only 6 of 1416 (0.42%) children had a positive dengue rapid test, while none of the RT-PCR results were positive. ELISA testing demonstrated reactive IgG antibodies in 28 (2.2%) participants with the highest prevalence seen at the urban site in Mbarara (19 of 392, 4.9%, p < 0.001). CONCLUSIONS: Overall, these findings suggest that dengue, while present, is an uncommon cause of non-malarial, pediatric febrile illness in western Uganda. Further investigation into the eocological factors that sustain low-level transmission in urban settings are urgently needed to reduce the risk of epidemics.


Assuntos
Vírus da Dengue/genética , Vírus da Dengue/imunologia , Dengue/diagnóstico , Dengue/epidemiologia , Febre/diagnóstico , Adolescente , Criança , Pré-Escolar , Dengue/virologia , Testes Diagnósticos de Rotina/efeitos adversos , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imunoglobulina G/imunologia , Imunoglobulina M/imunologia , Malária/diagnóstico , Malária/epidemiologia , Malária/parasitologia , Masculino , Plasmodium/imunologia , Plasmodium/isolamento & purificação , Prevalência , Estudos Prospectivos , Reação em Cadeia da Polimerase em Tempo Real , Estudos Soroepidemiológicos , Uganda/epidemiologia
2.
PLoS One ; 15(10): e0238609, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33112881

RESUMO

INTRODUCTION: Although immune responses to the Japanese Encephalitis virus (JEV), and the dengue viruses (DENV) have a potential to modulate the immune responses to each other, this has been poorly investigated. Therefore, we developed an ELISA to identify JEV specific, DENV non cross-reactive antibody responses by identifying JEV specific, highly conserved regions of the virus and proceeded to investigate if the presence of JEV specific antibodies associate with dengue disease severity. METHODOLOGY AND RESULTS: 22 JEV specific peptides were identified from highly conserved regions of the virus and the immunogenicity and specificity of these peptides were assessed in individuals who were non-immune to JEV and DENV (JEV-DENV-, N = 30), those who were only immune to the JEV and not DENV (JEV+DENV-, N = 30), those who were only immune to DENV(JEV-DENV+, N = 30) and in those who were immune to both viruses (JEV+DENV+, N = 30). 7/22 peptides were found to be highly immunogenic and specific and these 7 peptides were used as a pool to further evaluate JEV-specific responses. All 30/30 JEV+DENV- and 30/30 JEV+DENV+ individuals, and only 3/30 (10%) JEV-DENV+ individuals responded to this pool. We further evaluated this pool of 7 peptides in patients following primary and secondary dengue infection during the convalescent period and found that the JEV-specific peptides, were unlikely to cross react with DENV IgG antibodies. We further compared this in-house ELISA developed with the peptide pool with an existing commercial JEV IgG assay to identify JEV-specific IgG following vaccination, and our in-house ELISA was found to be more sensitive. We then proceeded to investigate if the presence of JEV-specific antibodies were associated with dengue disease severity, and we found that those who had past severe dengue (n = 175) were significantly more likely (p<0.0001) to have JEV-specific antibodies than those with past non-severe dengue (n = 175) (OR 5.3, 95% CI 3.3 to 8.3). CONCLUSIONS: As our data show that this assay is highly sensitive and specific for detection of JEV-specific antibody responses, it would be an important tool to determine how JEV seropositivity modulate dengue immunity and disease severity when undertaking dengue vaccine trials.


Assuntos
Anticorpos Antivirais/sangue , Vírus da Encefalite Japonesa (Espécie)/imunologia , Ensaio de Imunoadsorção Enzimática/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Sequência de Aminoácidos , Especificidade de Anticorpos , Criança , Sequência Conservada , Reações Cruzadas , Dengue/imunologia , Dengue/virologia , Vírus da Dengue/classificação , Vírus da Dengue/genética , Vírus da Dengue/imunologia , Vírus da Encefalite Japonesa (Espécie)/genética , Encefalite Japonesa/epidemiologia , Encefalite Japonesa/imunologia , Encefalite Japonesa/virologia , Ensaio de Imunoadsorção Enzimática/estatística & dados numéricos , Feminino , Voluntários Saudáveis , Humanos , Imunoglobulina G/sangue , Masculino , Pessoa de Meia-Idade , Fragmentos de Peptídeos/genética , Fragmentos de Peptídeos/imunologia , Sensibilidade e Especificidade , Estudos Soroepidemiológicos , Sorogrupo , Sri Lanka/epidemiologia , Vacinação , Proteínas Virais/genética , Proteínas Virais/imunologia , Adulto Jovem
4.
BMC Infect Dis ; 20(1): 639, 2020 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-32867694

RESUMO

BACKGROUND: Dengue fever is an arthropod vector-borne disease transmitted to humans by infected Aedes mosquitoes. Ethiopia has a favorable ecology for arthropods and report high burden of acute febrile illnesses. However, the contribution of arboviral infections to the burden of acute febrile illnesses is barely known. In this study the seropositivity to dengue virus infection and associated risk factors were assessed in Arba Minch districts, southern Ethiopia. METHODS: An institution based cross-sectional study was conducted in a consecutive group of 529 acute febrile patients between May to August 2016. Socio-demographic data, residence place and clinical signs and symptoms were collected using structured questionnaires. Sera were tested for anti-dengue IgG and IgM using Euroimmune indirect immunofluorescent assay. Data analysis was done using SPSS V-20 (IBM Corp, 2012). P-value < 0.05 was taken as statistically significant. RESULT: Seropositivity was 25.1% (133/529) and 8.1% (43/529) for anti- IgG and IgM respectively. CONCLUSION: The high IgM prevalence detected indicate the probability of active transmission with a potential of public health significance that calls for a proactive follow up of the communities in the study area to forecast and avert the risk.


Assuntos
Anticorpos Antivirais/sangue , Vírus da Dengue/imunologia , Dengue/sangue , Dengue/epidemiologia , Febre/sangue , Febre/epidemiologia , Adolescente , Adulto , Animais , Estudos Transversais , Dengue/diagnóstico , Dengue/virologia , Etiópia/epidemiologia , Feminino , Técnica Indireta de Fluorescência para Anticorpo , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Inquéritos e Questionários , Adulto Jovem
5.
Euro Surveill ; 25(36)2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32914745

RESUMO

In August 2020, during the coronavirus disease (COVID-19) pandemic, five locally acquired cases of dengue virus type 1 were detected in a family cluster in Vicenza Province, North-East Italy where Aedes albopictus mosquitoes are endemic. The primary case was an importation from West Sumatra, Indonesia. This is the first outbreak of autochthonous dengue reported in Italy. During the COVID-19 pandemic, screening of febrile travelers from endemic countries is crucial in areas where competent vectors are present.


Assuntos
Vírus da Dengue/isolamento & purificação , Dengue/diagnóstico , Viagem , Adulto , Pré-Escolar , Dengue/epidemiologia , Dengue/imunologia , Dengue/virologia , Vírus da Dengue/genética , Surtos de Doenças , Transmissão de Doença Infecciosa , Feminino , Febre/etiologia , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Indonésia , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , RNA Viral/sangue , Reação em Cadeia da Polimerase Via Transcriptase Reversa
6.
Sci Adv ; 6(39)2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32978154

RESUMO

Detection of viruses is critical for controlling disease spread. Recent emerging viral threats, including Zika virus, Ebola virus, and SARS-CoV-2 responsible for coronavirus disease 2019 (COVID-19) highlight the cost and difficulty in responding rapidly. To address these challenges, we develop a platform for low-cost and rapid detection of viral RNA with DNA nanoswitches that mechanically reconfigure in response to specific viruses. Using Zika virus as a model system, we show nonenzymatic detection of viral RNA with selective and multiplexed detection between related viruses and viral strains. For clinical-level sensitivity in biological fluids, we paired the assay with sample preparation using either RNA extraction or isothermal preamplification. Our assay requires minimal laboratory infrastructure and is adaptable to other viruses, as demonstrated by quickly developing DNA nanoswitches to detect SARS-CoV-2 RNA in saliva. Further development and field implementation will improve our ability to detect emergent viral threats and ultimately limit their impact.


Assuntos
Betacoronavirus/genética , Infecções por Coronavirus/diagnóstico , DNA de Cadeia Simples/genética , Eletroforese em Gel de Ágar/métodos , Pneumonia Viral/diagnóstico , RNA Viral/genética , Análise de Sequência de RNA/métodos , Sequência de Bases , Linhagem Celular Tumoral , Infecções por Coronavirus/virologia , Dengue/diagnóstico , Dengue/virologia , Vírus da Dengue/genética , Eletroforese em Gel de Ágar/economia , Humanos , Limite de Detecção , Pandemias , Pneumonia Viral/virologia , Saliva/virologia , Análise de Sequência de RNA/economia , Zika virus/genética , Infecção por Zika virus/diagnóstico , Infecção por Zika virus/virologia
7.
PLoS One ; 15(9): e0238431, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32886677

RESUMO

INTRODUCTION: Dengue fever is a re-emerging pathology in Burkina Faso. It affects everyone and pregnant women are not left out. The objective of this study was to estimate the burden of dengue fever and to assess its effects on pregnancy outcomes in hospitalized pregnant women during the 2017 outbreak in Ouagadougou, Burkina Faso. METHOD: This was a retrospective cohort study including febrile pregnant women from five health facilities in Ouagadougou. The study was carried out from July 1st to December 31st, 2017. A logistic stepwise regression was performed to identify the pregnancy adverse outcomes risk factors. RESULTS: Our study included 424 pregnant women at a mean age of 27.1 years old (Standard deviation: 6.23 years). Overall 28.54% (121/424) were infected with dengue virus. During follow-up, 29.01% (123/424) presented an adverse pregnancy outcome. Adjusted for gestational age and clinical symptoms, the risk of adverse pregnancy outcome was twice as high among dengue infected women as compared to uninfected women with an adjusted Odds Ratio (aOR) = 2.09 (1.08-4.05). The risk of the adverse pregnancy outcome was higher in the third trimester of pregnancy with aOR = 1.66 (1.02-2.72) in dengue fever infected women. CONCLUSION: Dengue fever is a risk factor for adverse pregnancy outcomes, especially in the third trimester in Burkina Faso. The implementation of effective anti-vectorial control interventions and better management of dengue fever during pregnancy are needed to improve pregnancy outcomes.


Assuntos
Dengue/epidemiologia , Resultado da Gravidez/epidemiologia , Adulto , Burkina Faso/epidemiologia , Estudos de Coortes , Dengue/virologia , Vírus da Dengue/patogenicidade , Surtos de Doenças , Feminino , Febre/etiologia , Humanos , Gravidez , Estudos Retrospectivos , Fatores de Risco
8.
BMC Infect Dis ; 20(1): 580, 2020 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-32762658

RESUMO

BACKGROUND: Dengue virus (DENV) causes the hospitalisation of an estimated 500,000 people every year. Outbreaks can severely stress healthcare systems, especially in rural settings. It is difficult to discriminate patients who need to be hospitalized from those that do not. Earlier work identified thrombocyte count and subsequent function as a promising prognostic marker of DENV severity. Herein, we investigated the potential of quantitative thrombocyte function tests in those admitted in the very early phase of acute DENV infections, using Multiplate™ multiple-electrode aggregometry to explore its potential in triage. METHODS: In this prospective cohort study all patients aged ≥13 admitted to Universitas Airlangga Hospital in Surabaya, Indonesia with a fever (≥38 °C) between 25 January and 1 August 2018 and with a clinical suspicion of DENV, were eligible for inclusion. Exclusion criteria were a thrombocyte count below 100 × 109/L and the use of any medication with a known anticoagulant effect, nonsteroidal anti-inflammatory drugs and acetyl salicylic acid. Clinical data was collected and blood was taken on admission, day 1 and day 7. Samples were tested for acute DENV, using Panbio NS1 ELISA. Platelet aggregation using ADP-, TRAP- and COL-test were presented as Area Under the aggregation Curve (AUC). Significance was tested between DENV+, probably DENV, fever of another origin, and healthy controls (HC). RESULTS: A total of 59 patients (DENV+ n = 10, DENV probable n = 25, fever other origin n = 24) and 20 HC were included. We found a significantly lower thrombocyte aggregation in the DENV+ group, compared with both HCs and the fever of another origin group (p < .001). Low ADP AUC values on baseline correlated to a longer hospital stay in DENV+ and probable DENV cases. CONCLUSION: Thrombocyte aggregation induced by Adenosine diphosphate, Collagen and Thrombin receptor activating peptide-6 is impaired in human DENV cases, compared with healthy controls and other causes of fever. This explorative study provides insights to thrombocyte function in DENV patients and could potentially serve as a future marker in DENV disease.


Assuntos
Plaquetas/metabolismo , Vírus da Dengue/imunologia , Dengue/diagnóstico , Dengue/epidemiologia , Sistemas Automatizados de Assistência Junto ao Leito , Testes Imediatos , Difosfato de Adenosina/sangue , Adolescente , Adulto , Idoso , Biomarcadores/sangue , Colágeno/metabolismo , Dengue/virologia , Ensaio de Imunoadsorção Enzimática , Feminino , Febre/diagnóstico , Humanos , Indonésia/epidemiologia , Masculino , Pessoa de Meia-Idade , Fragmentos de Peptídeos/sangue , Agregação Plaquetária , Contagem de Plaquetas , Estudos Prospectivos , Índice de Gravidade de Doença , Adulto Jovem
9.
BMC Infect Dis ; 20(1): 583, 2020 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-32762676

RESUMO

BACKGROUND: Dengue fever is endemic and a leading health problem in Sri Lanka. Increased incidence of concurrent bacteremia in patients with dengue infection is a recognized complication. However, Staphylococcal endocarditis following dengue fever is uncommon. Quadricuspid aortic valve (QAV) is a rare congenital anomaly and few cases of infective endocarditis have been reported in QAV. CASE PRESENTATION: A 32-year-old Sri Lankan male presented to the National Hospital of Sri Lanka with recurrence of fever and acute left hemiplegia following an uncomplicated recovery of dengue fever. He was diagnosed to have Staphylococcal infective endocarditis of quadricuspid aortic valve, with septic emboli to brain and spleen. He was managed with intravenous vancomycin initially, however, due to inadequate response, intravenous linezolid was added. He developed rhabdomyolysis with very high creatine phosphokinase leading to acute kidney injury, which settled with the cessation of linezolid. The patient succumbed to his illness despite aggressive antimicrobial therapy and maximum supportive care while being assessed for aortic valve replacement. CONCLUSIONS: This case illustrates three clinical issues that a clinician should be aware of. Firstly, the possibility of a serious secondary bacterial infection as a cause for recurrence of fever following dengue infection. Secondly, this case highlights the importance of identifying QAV as a cause for complicated infective endocarditis of increased severity. The report also denotes the value of being vigilant of linezolid induced rhabdomyolysis which had a causal relationship with the commencement of the drug and its cessation.


Assuntos
Valva Aórtica/anormalidades , Dengue/complicações , Endocardite Bacteriana/diagnóstico , Endocardite Bacteriana/etiologia , Doenças das Valvas Cardíacas/diagnóstico , Infecções Estafilocócicas/diagnóstico , Infecções Estafilocócicas/etiologia , Staphylococcus aureus/isolamento & purificação , Lesão Renal Aguda/etiologia , Lesão Renal Aguda/mortalidade , Adulto , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Bacteriemia/tratamento farmacológico , Hemocultura , Dengue/tratamento farmacológico , Dengue/virologia , Vírus da Dengue , Endocardite Bacteriana/tratamento farmacológico , Evolução Fatal , Febre/tratamento farmacológico , Humanos , Linezolida/farmacologia , Linezolida/uso terapêutico , Masculino , Rabdomiólise/induzido quimicamente , Rabdomiólise/complicações , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Acidente Vascular Cerebral/mortalidade
10.
Nat Rev Immunol ; 20(10): 633-643, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32782358

RESUMO

Antibody-dependent enhancement (ADE) is a mechanism by which the pathogenesis of certain viral infections is enhanced in the presence of sub-neutralizing or cross-reactive non-neutralizing antiviral antibodies. In vitro modelling of ADE has attributed enhanced pathogenesis to Fcγ receptor (FcγR)-mediated viral entry, rather than canonical viral receptor-mediated entry. However, the putative FcγR-dependent mechanisms of ADE overlap with the role of these receptors in mediating antiviral protection in various viral infections, necessitating a detailed understanding of how this diverse family of receptors functions in protection and pathogenesis. Here, we discuss the diversity of immune responses mediated upon FcγR engagement and review the available experimental evidence supporting the role of FcγRs in antiviral protection and pathogenesis through ADE. We explore FcγR engagement in the context of a range of different viral infections, including dengue virus and SARS-CoV, and consider ADE in the context of the ongoing SARS-CoV-2 pandemic.


Assuntos
Anticorpos Monoclonais/administração & dosagem , Anticorpos Antivirais/administração & dosagem , Anticorpos Facilitadores/efeitos dos fármacos , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Leucócitos/efeitos dos fármacos , Pneumonia Viral/tratamento farmacológico , Receptores de IgG/imunologia , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/biossíntese , Anticorpos Neutralizantes/administração & dosagem , Anticorpos Neutralizantes/efeitos adversos , Anticorpos Neutralizantes/biossíntese , Anticorpos Antivirais/efeitos adversos , Anticorpos Antivirais/biossíntese , Betacoronavirus/imunologia , Betacoronavirus/patogenicidade , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Dengue/tratamento farmacológico , Dengue/imunologia , Dengue/virologia , Vírus da Dengue/efeitos dos fármacos , Vírus da Dengue/imunologia , Vírus da Dengue/patogenicidade , Regulação da Expressão Gênica , Interações Hospedeiro-Patógeno/efeitos dos fármacos , Interações Hospedeiro-Patógeno/imunologia , Humanos , Leucócitos/imunologia , Leucócitos/virologia , Pandemias , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Receptores de IgG/antagonistas & inibidores , Receptores de IgG/genética , Vírus da SARS/efeitos dos fármacos , Vírus da SARS/imunologia , Vírus da SARS/patogenicidade , Síndrome Respiratória Aguda Grave/tratamento farmacológico , Síndrome Respiratória Aguda Grave/imunologia , Síndrome Respiratória Aguda Grave/virologia , Transdução de Sinais , Internalização do Vírus/efeitos dos fármacos
11.
PLoS Pathog ; 16(8): e1008754, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32776975

RESUMO

Arbovirus infection of Aedes aegypti salivary glands (SGs) determines transmission. However, there is a dearth of knowledge on SG immunity. Here, we characterized SG immune response to dengue, Zika and chikungunya viruses using high-throughput transcriptomics. We also describe a transcriptomic response associated to apoptosis, blood-feeding and lipid metabolism. The three viruses differentially regulate components of Toll, Immune deficiency (IMD) and c-Jun N- terminal Kinase (JNK) pathways. However, silencing of the Toll and IMD pathway components showed variable effects on SG infection by each virus. In contrast, regulation of the JNK pathway produced consistent responses in both SGs and midgut. Infection by the three viruses increased with depletion of the activator Kayak and decreased with depletion of the negative regulator Puckered. Virus-induced JNK pathway regulates the complement factor, Thioester containing protein-20 (TEP20), and the apoptosis activator, Dronc, in SGs. Individual and co-silencing of these genes demonstrate their antiviral effects and that both may function together. Co-silencing either TEP20 or Dronc with Puckered annihilates JNK pathway antiviral effect. Upon infection in SGs, TEP20 induces antimicrobial peptides (AMPs), while Dronc is required for apoptosis independently of TEP20. In conclusion, we revealed the broad antiviral function of JNK pathway in SGs and showed that it is mediated by a TEP20 complement and Dronc-induced apoptosis response. These results expand our understanding of the immune arsenal that blocks arbovirus transmission.


Assuntos
Aedes/imunologia , Apoptose , Febre de Chikungunya/imunologia , Proteínas do Sistema Complemento/imunologia , Dengue/imunologia , Sistema de Sinalização das MAP Quinases , Glândulas Salivares/imunologia , Infecção por Zika virus/imunologia , Aedes/virologia , Animais , Febre de Chikungunya/metabolismo , Febre de Chikungunya/prevenção & controle , Febre de Chikungunya/virologia , Vírus Chikungunya/imunologia , Proteínas do Sistema Complemento/metabolismo , Dengue/metabolismo , Dengue/prevenção & controle , Dengue/virologia , Vírus da Dengue/imunologia , Feminino , Interações Hospedeiro-Patógeno , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo , Insetos Vetores/imunologia , Insetos Vetores/virologia , Glândulas Salivares/virologia , Transcriptoma , Replicação Viral , Zika virus/imunologia , Infecção por Zika virus/metabolismo , Infecção por Zika virus/prevenção & controle , Infecção por Zika virus/virologia
12.
Am J Trop Med Hyg ; 103(3): 1223-1227, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32618241

RESUMO

Dengue-related mortality has significantly reduced with early and appropriate fluid resuscitation. However, we continue to see dengue-related fatalities in patients despite early intervention and advanced critical care support. This was a retrospective study conducted at a tertiary care private hospital in Mumbai, India. All patients dying of dengue in the calendar year 2017 were studied. Details related to age, gender, condition at presentation, laboratory parameters, treatment administered, and time to death were abstracted from case records. A total of 575 patients with a diagnosis of dengue were admitted to the hospital in 2017, of which 15 died (mortality rate 2.6%). Four patients died in the emergency medical unit; 11 patients who died after admission to the inpatient unit had multi-organ dysfunction at the time of presentation, with shock, severe liver dysfunction, and severe metabolic acidosis. Only 4/11 patients had hemoconcentration, and 10/11 patients had high white cell counts. In five patients where serum ferritin was performed, it was more than 40,000 ng/mL. Death occurred at a median time of 2 days after hospitalization despite good supportive care. Although there is scope for improvement of supportive care in these patients, it appears that other interventions are urgently needed to improve outcomes in severe dengue. This calls for more research into the immunopathology of dengue, evaluation of anti-inflammatory drugs, intravenous immunoglobulins, antivirals, and improved vaccines.


Assuntos
Dengue/diagnóstico , Dengue Grave/diagnóstico , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Cuidados Críticos , Dengue/imunologia , Dengue/terapia , Dengue/virologia , Feminino , Hidratação , Hospitalização , Hospitais Privados , Humanos , Índia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Dengue Grave/imunologia , Dengue Grave/terapia , Dengue Grave/virologia , Atenção Terciária à Saúde , Adulto Jovem
13.
Am J Trop Med Hyg ; 103(3): 970-975, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32602433

RESUMO

Nine criteria regarding the infectious agent, mode of transmission, portal of entry, route of spread, target organs, target cells, pathologic lesions, incubation period, and modifiable spectrum of disease and outcomes appropriate to the intended experimental purpose are described. To provide context for each criterion, mouse models of two vector-borne zoonotic infectious diseases, scrub typhus and dengue, are summarized. Application of the criteria indicates that intravenous inoculation of Orientia tsutsugamushi into inbred mice is the best current model for life-threatening scrub typhus, and intradermal inoculation accurately models sublethal human scrub typhus, whereas the immunocompromised mouse models of dengue provide disease outcomes most closely associated with human dengue. In addition to addressing basic questions of immune and pathogenic mechanisms, mouse models are useful for preclinical testing of experimental vaccines and therapeutics. The nine criteria serve as guidelines to evaluate and compare models of vector-borne infectious diseases.


Assuntos
Vírus da Dengue/imunologia , Dengue/imunologia , Modelos Animais de Doenças , Hospedeiro Imunocomprometido , Orientia tsutsugamushi/imunologia , Tifo por Ácaros/imunologia , Animais , Dengue/patologia , Dengue/virologia , Vírus da Dengue/patogenicidade , Humanos , Período de Incubação de Doenças Infecciosas , Injeções Intradérmicas , Injeções Intravenosas , Fígado/microbiologia , Fígado/virologia , Tecido Linfoide/microbiologia , Tecido Linfoide/virologia , Camundongos , Camundongos Knockout , Orientia tsutsugamushi/patogenicidade , Tifo por Ácaros/microbiologia , Tifo por Ácaros/patologia , Baço/microbiologia , Baço/virologia
14.
BMC Infect Dis ; 20(1): 466, 2020 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-32615988

RESUMO

BACKGROUND: Dengue fever is a major public health problem in Colombia. A fever surveillance study was conducted for evaluation of the clinical, epidemiological, and molecular patterns of dengue, prior to Chikungunya and Zika epidemics. METHODS: In November 2011-February 2014, a passive facility-based surveillance was implemented in Santa Cruz Hospital, Medellin, and enrolled eligible febrile patients between 1 and 65 years-of-age. Acute and convalescent blood samples were collected 10-21 days apart and tested for dengue using IgM/IgG ELISA. RNA was extracted for serotyping using RT-PCR on acute samples and genotyping was performed by sequencing. RESULTS: Among 537 febrile patients enrolled during the study period, 29% (n = 155) were identified to be dengue-positive. Only 7% of dengue cases were hospitalized, but dengue-positive patients were 2.6 times more likely to be hospitalized, compared to non-dengue cases, based on a logistic regression. From those tested with RT-PCR (n = 173), 17 were dengue-confirmed based on PCR and/or virus isolation showing mostly DENV-3 (n = 9) and DENV-4 (n = 7) with 1 DENV-1. Genotyping results showed that: DENV-1 isolate belongs to the genotype V or American/African genotype; DENV-3 isolates belong to genotype III; and DENV-4 isolates belong to the II genotype and specifically to the IIb sub-genotype or linage. CONCLUSIONS: Our surveillance documented considerable dengue burden in Santa Cruz comuna during non-epidemic years, and genetic diversity of circulating DENV isolates, captured prior to Chikungunya epidemic in 2014 and Zika epidemic in 2015. Our study findings underscore the need for continued surveillance and monitoring of dengue and other arboviruses and serve as epidemiological and molecular evidence base for future studies to assess changes in DENV transmission in Medellin, given emerging and re-emerging arboviral diseases in the region.


Assuntos
Vírus da Dengue/genética , Vírus da Dengue/imunologia , Dengue/epidemiologia , Febre/epidemiologia , Variação Genética , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Colômbia/epidemiologia , Dengue/virologia , Vírus da Dengue/isolamento & purificação , Doenças Endêmicas , Ensaio de Imunoadsorção Enzimática , Feminino , Febre/virologia , Genótipo , Humanos , Incidência , Lactente , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase Multiplex , Filogenia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Adulto Jovem
15.
PLoS Negl Trop Dis ; 14(7): e0008061, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32687540

RESUMO

Tanzania has recently experienced outbreaks of dengue in two coastal regions of Dar es Salaam and Tanga. Chikungunya and Rift Valley Fever outbreaks have also been recorded in the past decade. Little is known on the burden of the arboviral disease causing viruses (Dengue, Rift Valley and Chikungunya) endemically in the inter-epidemic periods. We aimed at determining the prevalence of the dengue, rift valley and chikungunya among humans in two geo ecologically distinct sites. The community-based cross-sectional study was conducted in Magugu in Manyara region and Wami-Dakawa in Morogoro region in Tanzania. Venous blood was collected from participants of all age groups, serum prepared from samples and subjected to ELISA tests for RVFV IgG/IgM, DENV IgG/IgM, and CHIKV IgM/IgG. Samples that were positive for IgM ELISA tests were subjected to a quantitative RT PCR for each virus. A structured questionnaire was used to collect socio-demographic information. Data analysis was performed by using SPSSv22. A total of 191 individuals from both sites participated in the study. Only one individual was CHIKV seropositive in Magugu, but none was seropositive or positive for either RVFV or DENV. Of the 122 individuals from Wami-Dakawa site, 16.39% (n = 20) had recent exposure to RVFV while 9.83% (n = 12) were seropositive for CHIKV. All samples were negative by RVFV and CHIKV qPCR. Neither infection nor exposure to DENV was observed in participants from both sites. Being more than 5 in a household, having no formal education and having recently travelled to an urban area were risk factors associated with RVFV and CHIKV seropositivity. We report a considerable exposure to RVFV and CHIKV among Wami-Dakawa residents during the dry season and an absence of exposure of the viruses among humans in Magugu site. In both sites, neither DENV exposure nor infection was detected.


Assuntos
Anticorpos Antivirais/sangue , Febre de Chikungunya/sangue , Vírus Chikungunya/imunologia , Vírus da Dengue/imunologia , Dengue/sangue , Febre do Vale de Rift/sangue , Vírus da Febre do Vale do Rift/imunologia , Adulto , Animais , Febre de Chikungunya/epidemiologia , Febre de Chikungunya/virologia , Vírus Chikungunya/fisiologia , Estudos Transversais , Dengue/epidemiologia , Dengue/virologia , Vírus da Dengue/fisiologia , Feminino , Humanos , Imunoglobulina M/sangue , Masculino , Pessoa de Meia-Idade , Febre do Vale de Rift/epidemiologia , Febre do Vale de Rift/virologia , Vírus da Febre do Vale do Rift/fisiologia , Estudos Soroepidemiológicos , Tanzânia/epidemiologia , Adulto Jovem
16.
Arch Virol ; 165(10): 2311-2315, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32638115

RESUMO

In the present study, an in-house-developed real-time RT-PCR (rRT-PCR) for serotyping of dengue virus (DENV) was evaluated for its performance, using 612 clinical samples. Compared to the composite reference standard, the in-house-developed rRT-PCR had an overall sensitivity of 97.5% and a specificity of 100%. The assay had a sensitivity of 100%, 95.6%. 96.9% and 100% for detecting DENV-1, DENV-2, DENV-3 and DENV-4, respectively. We recommend periodic evaluation of real-time RT-PCR assays for detecting DENV serotypes with a large number of samples and the use of at least two assays that target different regions of DENV genomes.


Assuntos
Vírus da Dengue/genética , Reação em Cadeia da Polimerase em Tempo Real/métodos , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Sorotipagem/métodos , Dengue/virologia , Humanos , Técnicas de Diagnóstico Molecular/métodos , RNA Viral/genética , Sensibilidade e Especificidade , Sorogrupo
17.
BMC Public Health ; 20(1): 905, 2020 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-32527239

RESUMO

BACKGROUND: Controlling sites where mosquitos breed is a key strategy in breaking the cycle of infectious transmission of the dengue virus. Preventive behaviors, such as covering water containers with lids and adding temephos (commercially named Abate sand) in water containers are needed to reduce and control mosquito breeding sites. This study aimed to investigate the impact of dengue-preventive behaviors on Aedes immature production. METHODS: This cross-sectional study used in-person interviews to record occurrence of dengue-preventive behaviors in Bang Kachao, Samut Prakan Province, Thailand. Larval mosquitos in and around houses were observed and recorded, and covered 208 households. RESULTS: It was found that 50% of these households had containers for drinking water and 94% used water containers. Covering water containers with effective lids showed the best success among dengue-preventive behaviors for reducing Aedes immature production. Adding temephos in water containers also was effective. CONCLUSIONS: Such behaviors substantively affected development of Aedes immatures in and around households.


Assuntos
Aedes/crescimento & desenvolvimento , Dengue/prevenção & controle , Características da Família , Larva/crescimento & desenvolvimento , Controle de Mosquitos/métodos , Abastecimento de Água , Água , Aedes/virologia , Animais , Estudos Transversais , Dengue/virologia , Vírus da Dengue/crescimento & desenvolvimento , Humanos , Larva/virologia , Temefós , Tailândia , Água/química
18.
BMC Public Health ; 20(1): 947, 2020 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-32546159

RESUMO

INTRODUCTION: Chikungunya and Zika Virus are vector-borne diseases responsible for a substantial disease burden in the Americas. Between 2013 and 2016, no cases of Chikungunya or Zika Virus were reported by the Venezuelan Ministry of Health. However, peaks of undiagnosed fever cases have been observed during the same period. In the context of scarce data, alternative surveillance methods are needed. Assuming that unusual peaks of acute fever cases correspond to the incidences of both diseases, this study aims to evaluate the use of Google Trends as an indicator of the epidemic behavior of Chikungunya and Zika. METHODS: Time-series cross-correlations of acute fever cases reported by the Venezuelan Ministry of Health and data on Google search queries related to Chikungunya and Zika were calculated. RESULTS: A temporal distinction has been made so that acute febrile cases occurring between 25th of June 2014 and 23rd of April 2015 were attributed to the Chikungunya virus, while cases occurring between 30th of April 2015 and 29th of April 2016 were ascribed to the Zika virus. The highest cross-correlations for each disease were shown at a lag of 0 (r = 0.784) for Chikungunya and at + 1 (r = 0.754) for Zika. CONCLUSION: The strong positive correlation between Google search queries and official data on acute febrile cases suggests that this resource can be used as an indicator of endemic urban arboviruses activity. In the Venezuelan context, Internet search queries might help to overcome some of the gaps that exist in the national surveillance system.


Assuntos
Arbovirus , Febre de Chikungunya/epidemiologia , Febre/etiologia , Comportamento de Busca de Informação , Internet , Vigilância da População/métodos , Infecção por Zika virus/epidemiologia , Febre de Chikungunya/complicações , Febre de Chikungunya/virologia , Vírus Chikungunya , Dengue/epidemiologia , Dengue/virologia , Vírus da Dengue , Epidemias , Febre/virologia , Órgãos Governamentais , Humanos , Incidência , Ferramenta de Busca/tendências , População Urbana , Venezuela/epidemiologia , Zika virus , Infecção por Zika virus/complicações , Infecção por Zika virus/virologia
19.
J Pharmacol Exp Ther ; 374(3): 500-511, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32532853

RESUMO

High-throughput cell-based fluorescent imaging assays often require removal of background fluorescent signal to obtain robust measurements. Processing high-density microplates to remove background signal is challenging because of equipment requirements and increasing variation after multiple plate wash steps. Here, we present the development of a wash-free cell-based fluorescence assay method for high-throughput screening using a laser scanning fluorescence plate cytometer. The cytometry data consisted of cell count and fluorescent intensity measurements for phenotypic screening. We obtained robust screening results by applying this assay methodology to the lysosomal storage disease Niemann-Pick disease type A. We further demonstrated that this cytometry method can be applied to the detection of cholesterol in Niemann-Pick disease type C. Lastly, we used the Mirrorball method to obtain preliminary results for the detection of Zika and Dengue viral envelope protein. The advantages of this assay format include 1) no plate washing, 2) 4-fold faster plate scan and analysis time, 3) high throughput, and 4) >10-fold smaller direct data files. In contrast, traditional imaging assays require multiple plate washes to remove the background signal, long plate scan and data analysis times, and large data files. Therefore, this versatile and broadly applicable Mirrorball-based method greatly improves the throughput and data quality of image-based screening by increasing sensitivity and efficiency while reducing assay artifacts. SIGNIFICANCE STATEMENT: This work has resulted in the development of broadly applicable cell-based fluorescence imaging assays without the requirement of washing out reagents to reduce background signal, which effectively decreases the need for extensive plate processing by the researcher. We demonstrate this high-throughput method for drug screening against lysosomal storage diseases and a commonly used viral titer assay.


Assuntos
Bioensaio/métodos , Ensaios de Triagem em Larga Escala/métodos , Células Cultivadas , Dengue/virologia , Vírus da Dengue/metabolismo , Avaliação Pré-Clínica de Medicamentos/métodos , Fluorescência , Humanos , Proteínas do Envelope Viral/metabolismo , Zika virus/metabolismo , Infecção por Zika virus/virologia
20.
Am J Trop Med Hyg ; 103(3): 1228-1233, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32588813

RESUMO

Zoonotic pathogens such as arboviruses have comprised a significant proportion of emerging infectious diseases in humans. The role of wildlife species as reservoirs for arboviruses is poorly understood, especially in endemic areas such as Southeast Asia. This study aims to determine the exposure history of different macaque species from national parks in Thailand to mosquito-borne flaviviruses and alphavirus by testing the serum samples collected from 25 northern pigtailed macaques, 33 stump-tailed macaques, and 4 long-tailed macaques for the presence of antibodies against dengue, Zika, and chikungunya viruses by plaque reduction neutralization assay. Specific neutralizing antibodies against Dengue virus (DENV1-4) and Zika virus (ZIKV) were mainly found in stump-tailed macaques, whereas neutralizing antibody titers were not detected in long-tailed macaques and pigtailed macaques as determined by 90% plaque reduction neutralization assay (PRNT90). One long-tailed macaque captured from the south of Thailand exhibited antibody titers against chikungunya virus (CHIKV), suggesting enzootic of this virus to nonhuman primates (NHPs) in Thailand. Encroachment of human settlements into the forest has increased the interface that exposes humans to zoonotic pathogens such as arboviruses found in monkeys. Nonhuman primates living in different regions of Thailand showed different patterns of arboviral infections. The presence of neutralizing antibodies among wild monkeys in Thailand strongly suggests the existence of sylvatic cycles for DENV, ZIKV, and CHIKV in Thailand. The transmission of dengue, Zika, and chikungunya viruses among wild macaques may have important public health implications.


Assuntos
Febre de Chikungunya/epidemiologia , Vírus Chikungunya/imunologia , Culicidae/virologia , Vírus da Dengue/imunologia , Dengue/epidemiologia , Infecção por Zika virus/epidemiologia , Zika virus/imunologia , Animais , Anticorpos Neutralizantes , Anticorpos Antivirais/sangue , Febre de Chikungunya/virologia , Dengue/virologia , Feminino , Geografia , Humanos , Macaca , Masculino , Mosquitos Vetores/virologia , Estudos Soroepidemiológicos , Tailândia/epidemiologia , Infecção por Zika virus/virologia
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