scholarly journals Field Deployment of a Mobile Biosafety Laboratory Reveals the Co-Circulation of Dengue Viruses Serotype 1 and Serotype 2 in Louga City, Senegal, 2017

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Idrissa Dieng ◽  
Maryam Diarra ◽  
Moussa Moïse Diagne ◽  
Martin Faye ◽  
Marie Henriette Dior Ndione ◽  
...  
Keyword(s):  
Phylogenetic Analysis ◽  
Dengue Virus ◽  
Wide Spectrum ◽  
Clinical Manifestations ◽  
Febrile Illness ◽  
Field Investigation ◽  
Severe Dengue ◽  
Outbreak Response ◽  
Human Sera ◽  
Field Deployment

Dengue virus (DENV) is the most prevalent arboviral threat worldwide. This virus belonging to genus Flavivirus, Flaviviridae family, is responsible for a wide spectrum of clinical manifestations, ranging from asymptomatic or mild febrile illness (dengue fever) to life-threatening infections (severe dengue). Many sporadic cases and outbreaks have occurred in Senegal since 1970. Nevertheless, this article describes a field investigation of suspected dengue cases, between 05 September 2017 and 17 December 2017 made possible by the deployment of a Mobile Biosafety Laboratory (MBS-Lab). Overall, 960 human sera were collected and tested in the field for the presence of viral RNA by real-time RT-PCR. Serotyping, sequencing of complete E gene, and phylogenetic analysis were also performed. Out of 960 suspected cases, 131 were confirmed dengue cases. The majority of confirmed cases were from Louga community. Serotyping revealed two serotypes, Dengue 1 (100/104; 96, 15%) and Dengue 2 (04/104; 3, 84%). Phylogenetic analysis of the sequences obtained indicated that the Dengue 1 strain was closely related to strains isolated, respectively, in Singapore (Asia) in 2013 (KX380803.1) outbreak and it cocirculated with a Dengue 2 strain closely related to strains from a Burkina Faso dengue outbreak in 2016 (KY62776.1). Our results showed the co-circulation of two dengue virus serotypes during a single outbreak in a short time period. This co-circulation highlighted the need to improve surveillance in order to prevent future potential severe dengue cases through antibody-dependent enhancement (ADE). Interestingly, it also proved the reliability and usefulness of the MBS-Lab for expedient outbreak response at the point of need, which allows early cases management.

scholarly journals Complete assembly of a dengue virus type 3 genome from a recent genotype III clade by metagenomic sequencing of serum

2019 ◽  
Vol 3 ◽  
pp. 44 ◽  
Author(s):  
Mary Dias ◽  
Chitra Pattabiraman ◽  
Shilpa Siddappa ◽  
Malali Gowda ◽  
Anita Shet ◽  
...  
Keyword(s):  
Dengue Virus ◽  
Virus Type ◽  
Tertiary Care ◽  
Febrile Illness ◽  
Severe Dengue ◽  
Metagenomic Sequencing ◽  
Tertiary Care Centre ◽  
Genotype Iii ◽  
Dengue Virus Type 3 ◽  
Type 3

Background: Mosquito-borne flaviviruses, such as dengue and Japanese encephalitis virus (JEV), cause life-threatening diseases, particularly in the tropics. Methods: Here we performed unbiased metagenomic sequencing of RNA extracted from the serum of four patients and the plasma of one patient, all hospitalized at a tertiary care centre in South India with severe or prolonged febrile illness, together with the serum from one healthy control, in 2014. Results: We identified and assembled a complete dengue virus type 3 sequence from a case of severe dengue fever. We also identified a small number of JEV sequences in the serum of two adults with febrile illness, including one with severe dengue. Phylogenetic analysis revealed that the dengue sequence belonged to genotype III. It has an estimated divergence time of 13.86 years from the most highly related Indian strains. In total, 11 amino acid substitutions were predicted for this strain in the antigenic envelope protein, when compared to the parent strain used for development of the first commercial dengue vaccine.  Conclusions: We demonstrate that both genome assembly and detection of a low number of viral sequences are possible through the unbiased sequencing of clinical material. These methods may help ascertain causal agents for febrile illnesses with no known cause.

scholarly journals Addition of Partial Envelope Domain II into Envelope Domain III of Dengue Virus Antigen Potentiates the Induction of Virus-Neutralizing Antibodies and Induces Protective Immunity

Vaccines ◽  
2020 ◽  
Vol 8 (1) ◽  
pp. 88 ◽  
Author(s):  
Jisang Park ◽  
Hyun-Young Lee ◽  
Ly Tuan Khai ◽  
Nguyen Thi Thu Thuy ◽  
Le Quynh Mai ◽  
...  
Keyword(s):  
Dengue Virus ◽  
Dengue Fever ◽  
Neutralizing Antibodies ◽  
Subunit Vaccine ◽  
Secondary Infection ◽  
Febrile Illness ◽  
Hemorrhagic Fever ◽  
Denv Infection ◽  
Severe Dengue ◽  
Domain Iii

Dengue virus (DENV) comprises four serotypes in the family Flaviviridae and is a causative agent of dengue-related diseases, including dengue fever. Dengue fever is generally a self-limited febrile illness. However, secondary infection of patients with a suboptimal antibody (Ab) response provokes life-threatening severe dengue hemorrhagic fever or dengue shock syndrome. To develop a potent candidate subunit vaccine against DENV infection, we developed the EDII-cEDIII antigen, which contains partial envelope domain II (EDII) including the fusion loop and BC loop epitopes together with consensus envelope domain III (cEDIII) of all four serotypes of DENV. We purified Ab from mice after immunization with EDII-cEDIII or cEDIII and compared their virus neutralization and Ab-dependent enhancement of DENV infection. Anti-EDII-cEDIII Ab showed stronger neutralizing activity and lower Ab-dependent peak enhancement of DENV infection compared with anti-cEDIII Ab. Following injection of Ab-treated DENV into AG129 mice, anti-EDII-cEDIII Ab ameliorated DENV infection in tissues with primary and secondary infection more effectively than anti-cEDIII Ab. In addition, anti-EDII-cEDIII Ab protected against DENV1, 2, and 4 challenge. We conclude that EDII-cEDIII induces neutralizing and protective Abs, and thus, shows promise as a candidate subunit vaccine for DENV infection.

scholarly journals Complete assembly of a dengue virus type 3 genome from a recent genotype III clade by metagenomic sequencing of serum

2017 ◽  
Author(s):  
Chitra Pattabiraman ◽  
Mary Dias ◽  
Shilpa Siddappa ◽  
Malali Gowda ◽  
Anita Shet ◽  
...  
Keyword(s):  
Dengue Virus ◽  
Virus Type ◽  
Japanese Encephalitis ◽  
Febrile Illness ◽  
Severe Dengue ◽  
Sequence Information ◽  
Metagenomic Sequencing ◽  
Genotype Iii ◽  
Dengue Virus Type 3 ◽  
Type 3

ABSTRACTBackgroundMosquito-borne flaviviruses causing diseases such as dengue and Japanese encephalitis are devastating, particularly in the tropics. Although, multiple flaviviruses are known to co-circulate in India, when a patient presents with febrile illness, testing is usually limited to specific pathogens. Unbiased metagenomic sequencing of febrile cases can reveal the presence of multiple pathogens and provide complete genome information. Sequence information, a cornerstone for tracing virus evolution, is relevant for the design of vaccines and therapeutics. In order to assess the usefulness of unbiased metagenomic sequencing for the identification of viruses associated with febrile illness, we sequenced serum from four individuals and plasma from one individual, all hospitalized at a tertiary care centre in South India with severe or prolonged febrile illnesses, together with one healthy control in 2014.ResultsWe identified and assembled a complete dengue virus type 3 (DENV3) sequence from the serum of a case classified as severe dengue. We also found a small number of Japanese encephalitis virus (JEV) sequences in the serum of two adults with febrile illness, including the one who had dengue. Phylogenetic analysis of the dengue sequence indicates that it belongs to a predominantly Asian, DENV3, genotype III clade. It had an estimated divergence time of 13.86 years (95% Highest Posterior Densities 12.94 - 14.83 years) with the closest Indian strain. Amino acid substitutions were present throughout the sequenced genome, including 11 substitutions in the antigenic envelope protein compared to the strain used for the development of the first commercial dengue vaccine. Of these one substitution (E361D) was unique and six were in critical antigenic sites.ConclusionsWe demonstrate that both genome assembly and detection of a low number of viral sequences are possible by unbiased sequencing of clinical material. Complete dengue virus sequence analysis places the sequenced genome in a recent, predominantly Asian clade within genotype III of DENV3. The detection of JEV, an agent not routinely tested in febrile illness in India, warrants further analysis and highlights the need to study co-circulating flaviviruses in parallel.

scholarly journals Karakteristik Klinis dan Virologis Penderita Demam Berdarah Dengue di Kota Bandar Lampung

2020 ◽  
Vol 12 (2) ◽  
pp. 85-92
Author(s):  
Nurminha Nurminha ◽  
Tori Rihiantoro ◽  
Mara Ipa
Keyword(s):  
Dengue Virus ◽  
Clinical Symptoms ◽  
Serological Test ◽  
Secondary Infection ◽  
Dengue Infection ◽  
Clinical Manifestations ◽  
Denv Infection ◽  
Severe Dengue ◽  
Virus Serotype ◽  
Degree Of Severity

Abstract. Clinical symptoms of dengue virus (DENV) infection range from asymptomatic mild dengue fever(DF), more severe dengue hemorrhagic fever (DHF) up to dengue shock syndrome. One of the determinantsof dengue infection severity was virus virulence. This study aimed to determine the clinical and virologicalcharacteristics of dengue virus infection patients based on the severity degree. A cross-sectional study wasconducted in RSUD Dr. H. Abdul Moeloek, Lampung Province between July-November 2016 with 56 denguepatients as samples selected using purposive sampling. The serological test was done using a rapiddiagnostic test. Blood samples for DENV serotype identification were examined using reverse-transcriptionpolymerase chain reaction. Classification of DENV infection severity was obtained from the patient’s medicalrecord. The results showed that the most common clinical manifestations were fever, headache, and retroorbitalpain, appearing in all patients from every degree of severity. There were Grade I DHF patients whoexperienced Myalgia (15.6%) and petechiae (22.2%). Laboratory results showed that thrombocytopeniaappeared in every grade, even though 13.3% of grade I patients did not experience it. Secondary infectionwas found in 92.9% of samples, and all DENV serotype can be detected in 39.2%samples: DENV-1 (46.7%),DENV-2 (6.7%), DENV-3 (26.7%), and DENV-4 (20%). This study concluded that the majority of clinicalcharacteristics in DHF patients are in line with the degree of severity, with the bleeding as the dominantmanifestation in patients with grade II-IV. Virological characteristics of DENV-1 are dominant in all patientswith DHF grade I-IV.Keywords: dengue virus, serotype, severity, secondary infection, Bandar Lampung

scholarly journals Frequency and Clinical Manifestations of Dengue in Urban Medellin, Colombia

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Berta Nelly Restrepo ◽  
Mark E. Beatty ◽  
Yenny Goez ◽  
Ruth E. Ramirez ◽  
G. William Letson ◽  
...  
Keyword(s):  
Dengue Virus ◽  
Dengue Fever ◽  
Low Income ◽  
Dengue Infection ◽  
Diagnostic Testing ◽  
Clinical Manifestations ◽  
Febrile Illness ◽  
Hemorrhagic Fever ◽  
Dengue Virus Infection ◽  
Medical Facilities

A dengue fever surveillance study was conducted at three medical facilities located in the low-income district of San Javier in Medellin, Colombia. During March 2008 to 2009, 781 patients with fever regardless of chief complaint were recruited for acute dengue virus infection testing. Of the 781 tested, 73 (9.3%) were positive for dengue infection. Serotypes DENV-2 (77%) and -3 (23%) were detected by PCR. One patient met the diagnostic criteria for dengue hemorrhagic fever. Only 3 out of 73 (4.1%) febrile subjects testing positive for dengue infection were diagnosed with dengue fever by the treating physician. This study confirms dengue virus as an important cause of acute febrile illness in Medellin, Colombia, but it is difficult to diagnose without dengue diagnostic testing.

scholarly journals Viral Toxin NS1 Implication in Dengue Pathogenesis Making It a Pivotal Target in Development of Efficient Vaccine

Vaccines ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 946
Author(s):  
Grégorie Lebeau ◽  
Alisé Lagrave ◽  
Eva Ogire ◽  
Lauriane Grondin ◽  
Soundary Seriacaroupin ◽  
...  
Keyword(s):  
Vaccine Development ◽  
Current Knowledge ◽  
Nonstructural Protein ◽  
Wide Spectrum ◽  
Clinical Manifestations ◽  
Public Health Problem ◽  
Severe Dengue ◽  
Global Public Health ◽  
Dengue Disease ◽  
Nonstructural Protein 1

The mosquito-borne viral disease dengue is a global public health problem causing a wide spectrum of clinical manifestations ranging from mild dengue fever to severe dengue with plasma leakage and bleeding which are often fatal. To date, there are no specific medications to treat dengue and prevent the risk of hemorrhage. Dengue is caused by one of four genetically related but antigenically distinct serotypes DENV-1–DENV-4. The growing burden of the four DENV serotypes has intensified both basic and applied research to better understand dengue physiopathology. Research has shown that the secreted soluble hexameric form of DENV nonstructural protein-1 (sNS1) plays a significant role in the pathogenesis of severe dengue. Here, we provide an overview of the current knowledge about the role of sNS1 in the immunopathogenesis of dengue disease. We discuss the potential use of sNS1 in future vaccine development and its potential to improve dengue vaccine efficiency, particularly against severe dengue illness.

scholarly journals Viral Toxin ns1 as Pivotal Target in Development of Efficient Dengue Vaccine

2021 ◽  
Author(s):  
Grégorie Lebeau ◽  
Alisé Lagrave ◽  
Eva Ogire ◽  
Lauriane Grondin ◽  
Soundary Seriacaroupin ◽  
...  
Keyword(s):  
Current Knowledge ◽  
Nonstructural Protein ◽  
Wide Spectrum ◽  
Clinical Manifestations ◽  
Public Health Problem ◽  
Severe Dengue ◽  
Global Public Health ◽  
Dengue Vaccine ◽  
Dengue Disease ◽  
Nonstructural Protein 1

Mosquito-borne viral disease dengue is a global public health problem causing a wide spectrum of clinical manifestations ranging from mild dengue fever to severe dengue with plasma leakage and bleeding which are often associated to fatality. To date, there are no specific medications to treat dengue and prevent the risk of hemorrhage. Dengue is caused by one of the four related antigenically distinct serotypes, DENV-1 to DENV-4. The growing burden that represents the four DENV serotypes has intensified both basic and applied researches to better understand the dengue physiopathology. It has been proposed a significant role for the secreted soluble DENV nonstructural protein 1 (sNS1) glycoprotein in the pathogenesis of severe dengue. Here, we provided an overview on current knowledge about the role of sNS1 in the immunopathogenesis of dengue disease. The reasons for the consideration of sNS1 in the design of future dengue vaccine candidates will be discussed.

scholarly journals Antiviral Evaluation of UV-4B and Interferon-Alpha Combination Regimens against Dengue Virus

Viruses ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 771
Author(s):  
Evelyn J. Franco ◽  
Camilly P. Pires de Mello ◽  
Ashley N. Brown
Keyword(s):  
Dengue Virus ◽  
Cell Lines ◽  
Interferon Alpha ◽  
Plaque Assay ◽  
Clinical Manifestations ◽  
Cell Types ◽  
Vero Cells ◽  
Human Infection ◽  
Severe Dengue ◽  
Viral Burden

Dengue virus (DENV) is a flavivirus associated with clinical manifestations ranging in severity from self-limiting dengue fever, to the potentially life threatening condition, severe dengue. There are currently no approved antiviral therapies for the treatment of DENV. Here, we evaluated the antiviral potential of four broad-spectrum antivirals, UV-4B, interferon-alpha (IFN), sofosbuvir (SOF), and favipiravir (FAV) against DENV serotype 2 as mono- and combination therapy in cell lines that are physiologically relevant to human infection. Cell lines derived from human liver (HUH-7), neurons (SK-N-MC), and skin (HFF-1) were infected with DENV and treated with UV-4B, IFN, SOF, or FAV. Viral supernatant was sampled daily and infectious viral burden was quantified by plaque assay on Vero cells. Drug effect on cell proliferation in uninfected and infected cells was also assessed. UV-4B inhibited DENV in HUH-7, SK-N-MC, and HFF-1 cells yielding EC50 values of 23.75, 49.44, and 37.38 µM, respectively. Clinically achievable IFN concentrations substantially reduced viral burden in HUH-7 (EC50 = 102.7 IU/mL), SK-N-MC (EC50 = 86.59 IU/mL), and HFF-1 (EC50 = 163.1 IU/mL) cells. SOF potently inhibited DENV in HUH-7 cells but failed to produce the same effect in SK-N-MC and HFF-1 cells. Finally, FAV provided minimal suppression in HUH-7 and SK-N-MC cells, but was ineffective in HFF-1 cells. The two most potent anti-DENV agents, UV-4B and IFN, were also assessed in combination. UV-4B + IFN treatment enhanced antiviral activity in HUH-7, SK-N-MC, and HFF-1 cells relative to monotherapy. Our results demonstrate the antiviral potential of UV-4B and IFN against DENV in multiple physiologically relevant cell types.

scholarly journals LINFOHISTIOCITOSIS HEMOFAGOCÍTICA ASOCIADA AL DENGUE GRAVE

2021 ◽  
Vol 6 (4) ◽  
pp. 65
Author(s):  
Nereida Josefina Valero ◽  
Lisbeth Georgina Polanco Peláez ◽  
Marcos Jacob Sacan Arriola
Keyword(s):  
Dengue Virus ◽  
Natural Killer ◽  
Hemophagocytic Lymphohistiocytosis ◽  
Hemophagocytic Syndrome ◽  
Clinical Manifestations ◽  
Signs And Symptoms ◽  
Severe Dengue ◽  
Timely Diagnosis ◽  
Palabras Clave ◽  
Revisión Sistemática

La linfohistiocitosis hemofagocítica (LHH) es una enfermedad que afecta al sistema inmunitario, a través de la activación macrofágica descontrolada, con falla en las funciones de las células asesinas natural killer (NK) y los linfocitos T citotóxicos. El dengue es la arbovirosis de mayor impacto en salud pública, que se presenta en áreas tropicales del mundo. El objetivo de esta investigación fue analizar la asociación de la linfohistiocitosis hemofagocítica a la severidad del dengue, síntomas y diagnóstico. Se aplicó una metodología con diseño documental con revisión sistemática de la bibliografía en las bases de datos científicas y buscadores PubMed, Medline, Scielo, Elsevier y Google Académico, utilizando las palabras clave: síndrome hemofagocítico, linfohistiocitosis hemofagocítica, virus dengue, dengue grave, natural killer e inflamación. Se seleccionaron 85 artículos bajo criterios de inclusión y exclusión, tanto en inglés como en español, publicados entre los años 2010-2021. El síndrome hemofagocítico es el responsable de los síntomas que en determinado momento prolongan o complican el dengue grave, se caracteriza por una activación inmune patológica, con signos y síntomas de inflamación excesiva, donde sus principales manifestaciones clínicas son fiebre, citopenias, esplenomegalias, hemofagocitosis, hipertrigliceridemia e hipofibrinogenemia, teniendo encuentra que el problema principal en esta patología es el diagnóstico oportuno, dado que su presentación generalmente esta enmascarada por la enfermedad viral que usualmente se convierte en el desencadenante, y la persistencia o progresión de los síntomas suele ser pasada por alto. La LHH asociada al dengue se encuentra descrita como una forma inusual y grave, lo que da como resultado una tormenta de citocinas liberadas durante la enfermedad. La asociación entre ambas entidades causa manifestaciones clínicas amplias que pueden iniciar desde lo menos grave hasta lo hemorrágico, el cuadro febril, dolor abdominal y dificultad respiratoria, entre otras manifestaciones clínicas, resaltan, lo cual debe orientar al diagnóstico oportuno y evitar la muerte del paciente. Palabras clave: síndrome hemofagocítico linfohistiocitosis, virus dengue, dengue grave, dengue severo, natural killer.   ABSTRACT Hemophagocytic lymphohistiocytosis (HHL) is a disease that affects the immune system, through uncontrolled macrophage activation, with failure of natural killer (NK) cells and cytotoxic T lymphocytes. Dengue is the arbovirus with the greatest impact on public health, occurring in tropical areas of the world. The objective of this research was to analyze the association of hemophagocytic lymphohistiocytosis with the severity of dengue, symptoms and diagnosis. A documentary design methodology was applied with a systematic review of the bibliography in the scientific databases and search engines PubMed, Medline, Scielo, Elsevier and Google Scholar, using the key words: hemophagocytic syndrome, hemophagocytic lymphohistiocytosis, dengue virus, severe dengue, natural killer and inflammation. 85 articles were selected under inclusion and exclusion criteria, both in English and Spanish, published between 2010-2021. Hemophagocytic syndrome is responsible for the symptoms that at a certain time prolong or complicate severe dengue, it is characterized by pathological immune activation, with signs and symptoms of excessive inflammation, where its main clinical manifestations are fever, cytopenias, splenomegaly, hemophagocytosis, hypertriglyceridemia and hypofibrinogenemia, having found that the main problem in this pathology is timely diagnosis, since its presentation is generally masked by the viral disease that usually becomes the trigger, and the persistence or progression of symptoms is often overlooked. Dengue-associated LHH is described as an unusual and severe form, resulting in a storm of cytokines released during the disease. The association between both entities causes wide clinical manifestations that can start from the less severe to the hemorrhagic, the feverish picture, abdominal pain and respiratory distress, among other clinical manifestations, they highlight, which should guide the timely diagnosis and avoid the death of the patient. Keywords: hemophagocytic lymphohistiocytosis syndrome, dengue virus, severe dengue, severe dengue, natural killer.

scholarly journals Pathogenesis of Dengue virus in Host immune system and its genomic variation

2021 ◽  
Vol 6 (1) ◽  
pp. 16-30
Author(s):  
Sohail Sohail ◽  
Mukarram Farooq ◽  
Fareeha Sohail ◽  
Hamza Rana ◽  
Husnain Karim ◽  
...  
Keyword(s):  
T Cells ◽  
Dengue Virus ◽  
Febrile Illness ◽  
Dengue Shock Syndrome ◽  
Hemorrhagic Fever ◽  
Genomic Variation ◽  
Severe Dengue ◽  
Host Immune System ◽  
Ns1 Protein ◽  
Protein Cleavage

Dengue viruses are the most prevalent arthropod-borne viral diseases in humans, infecting 50-100 million people each year. Its serotypes are the most common causes of arboviral illness, putting half of the world's population at risk of infection. Because there is no vaccine or antiviral medicines, the only way to manage the disease is to reduce the Aedes mosquito vectors. DENV infection can be asymptomatic or cause a self-limiting, acute febrile illness with varying degrees of severity. High fever, headache, stomach discomfort, rash, myalgia, and arthralgia are the typical symptoms of dengue fever (DF). Thrombocytopenia, vascular leakage, and hypotension are symptoms of severe dengue, dengue hemorrhagic fever (DHF), and dengue shock syndrome (DSS). Systemic shock characterizes DSS, which can be deadly. Dengue virus infection pathogenesis is linked to a complex interaction between virus, host genes, and host immune response. Major drivers of disease vulnerability include host factors such as antibody-dependent enhancement (ADE), memory cross-reactive T cells, anti-DENV NS1 antibodies, autoimmunity, and genetic variables. The NS1 protein and anti-DENV NS1 antibodies were thought to be involved in the development of severe dengue. The progressive infection may change the cytokine response of cross reactive CD4+ T cells. The need for dengue vaccines that can generate strong protective immunity against all four serotypes is required. To create such vaccines, a thorough understanding of DENV adaptive immunity is required. Structural and functional research have shown that the degree of prM protein cleavage as well as the ensemble of conformational states sampled by virions influence DENV sensitivity to antibody-mediated neutralization, which has crucial implications for vaccine formulation.

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