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Annals of Clinical Microbiology and... Feb 2018Dengue is a global health problem and expansion of its endemics towards new territories in the hilly regions in Nepal is a serious concern. It appeared as a new disease... (Review)
Review
Dengue is a global health problem and expansion of its endemics towards new territories in the hilly regions in Nepal is a serious concern. It appeared as a new disease in Nepal in 2004 from Japanese traveler with sporadic cases every year and massive outbreaks in 2010, 2013 and 2016. The serotype was responsible for outbreak in particular year was dengue virus serotype-1 (DENV-1) in 2010, 2016; and DENV-2 in 2013. Nepal lacks basic health related infrastructure in rural areas and does not have a stringent health care policy. With severances of epidemic like dengue, a new surveillance or an upgrading of existing one are direly needed to better challenge the possible outbreaks. This review paper aims to explain the dengue trend in last one decade in Nepal and warrants concerted and timely public health interventions to minimize the deleterious effects of the disease.
Topics: Adolescent; Adult; Age Factors; Dengue; Dengue Virus; Disease Outbreaks; Epidemics; Female; Health Policy; Humans; Male; Nepal; Public Health; Seasons; Serogroup; Sex Factors; Young Adult
PubMed: 29471819
DOI: 10.1186/s12941-018-0258-9 -
Current Opinion in Virology Jun 2016Recent evidence has revealed that asymptomatic and/or persistent dengue virus (DENV) infections play a role in the cycling pattern of dengue outbreaks. These findings... (Review)
Review
Recent evidence has revealed that asymptomatic and/or persistent dengue virus (DENV) infections play a role in the cycling pattern of dengue outbreaks. These findings add a new dimension to the continually evolving search for effective prevention strategies in dengue. Disappointing outcomes of clinical trials in anti-dengue modalities have become commonplace. These failures may result from confounding variables and/or unresolved scientific issues that surround dengue, including the replication cycle of DENV in a natural setting, the target cells and reservoir for viral replication in vivo, and the effect of asymptomatic/persistent carriers in the dissemination of dengue. This article sets forth to address these issues using the most updated information available in the literature and to propose a novel antiviral strategy for the prevention and control of dengue.
Topics: Aedes; Animals; Antiviral Agents; Asymptomatic Infections; Carrier State; Dengue; Dengue Virus; Humans; Viremia; Virion; Virus Replication
PubMed: 27284691
DOI: 10.1016/j.coviro.2016.05.009 -
Archives of Virology Apr 2016Dengue virus infection (DVI)/dengue hemorrhagic fever (DHF) is a common febrile illness with a variety of severities. The mortality rate is high in dengue shock syndrome... (Review)
Review
Dengue virus infection (DVI)/dengue hemorrhagic fever (DHF) is a common febrile illness with a variety of severities. The mortality rate is high in dengue shock syndrome (DSS), caused by circulatory failure due to plasma leakage resulting in multi-organ failure. However, acute kidney injury (AKI) is rarely reported. In areas of endemic DVI, the prevalence of AKI due to DVI has been reported to be as high as 6.0 % in children with AKI, and 0.9 % in children with DVI who were admitted to a hospital. The mechanism of AKI in DVI is not clear. It may result from (a) direct injury as in other infectious diseases, (b) an indirect mechanism such as via the immune system, since DHF is an immunological disease, or (c) hypotensive DSS, leading in turn to reduced renal blood supply and renal failure. The mortality rates of DF/DHF, DSS and DHF/DSS-related AKI are <1 %, 12-44 %, and >60 %, respectively. Kidney involvement is not actually that rare, but is under-recognized and often only reported when microscopic hematuria, proteinuria, electrolyte imbalance, or even AKI is found. The prevalence of proteinuria and hematuria has been reported as high as 70-80 % in DVI. A correct diagnosis depends on basic investigations of kidney function such as urinalysis, serum creatinine and electrolytes. Although DVI-related renal involvement is treated supportively, it is still important to make an early diagnosis to prevent AKI and its complications, and if AKI does occur, dialysis may be required. Fortunately, in patients who recover, kidney function usually completely recovers as well.
Topics: Acute Kidney Injury; Dengue Virus; Humans; Risk Factors; Severe Dengue
PubMed: 26699788
DOI: 10.1007/s00705-015-2727-1 -
Antimicrobial Agents and Chemotherapy Jun 2017Zika virus (ZIKV), a flavivirus transmitted by mosquitoes, was an almost neglected pathogen until its introduction in the Americas in 2015 and its subsequent explosive... (Review)
Review
Zika virus (ZIKV), a flavivirus transmitted by mosquitoes, was an almost neglected pathogen until its introduction in the Americas in 2015 and its subsequent explosive spread throughout the continent, where it has infected millions of people. The virus has caused social and sanitary alarm, mainly due to its association with severe neurological disorders (Guillain-Barré syndrome and microcephaly in fetuses and newborns). Nowadays, no specific antiviral therapy against ZIKV is available. However, during the past months, a great effort has been made to search for antiviral candidates using different approaches and methodologies, ranging from testing specific compounds with known antiviral activity to the screening of libraries with hundreds of bioactive molecules. The identified antiviral candidates include drugs targeting viral components as well as cellular ones. Here, an updated review of what has been done in this line is presented.
Topics: Animals; Antiviral Agents; Dengue Virus; Guillain-Barre Syndrome; Humans; Protease Inhibitors; Viral Proteins; Zika Virus
PubMed: 28348160
DOI: 10.1128/AAC.00411-17 -
Advances in Experimental Medicine and... 2018Dengue is the most important mosquito-borne viral disease in the world, representing a major unmet medical need and a growing public health concern. The disease imposes... (Review)
Review
Dengue is the most important mosquito-borne viral disease in the world, representing a major unmet medical need and a growing public health concern. The disease imposes a heavy burden to the affected individuals, to the health care systems, and to the economies of endemic countries. Vector control is the most widespread tool to curb dengue epidemics, but has been insufficient. Therefore, additional means such as vaccines and antivirals are required to aid in a coordinated response. The discovery and development of small molecule dengue virus inhibitors as a tool to prevent and/or treat dengue disease faces major hurdles in combining pan-serotypic efficacy, safety, and optimal drug-like properties. Moreover, the financial return of dengue drug projects may not compensate for the initial investment in research and development. This review article addresses the efforts undertaken to face the dengue epidemics, focusing on antiviral drug development. The dengue drug research and development process is described in detail and a dengue antiviral target product profile is proposed. The article discusses collaborations between the different players in the research field: government and government-sponsored organizations, pharmaceutical and biotechnology companies, academia, and non-profit and philanthropic organizations. Public-private partnerships are proposed as a model to boost dengue research and development towards an approved antiviral drug in the near future.
Topics: Animals; Antiviral Agents; Dengue; Dengue Virus; Drug Discovery; Drug Industry; History, 20th Century; History, 21st Century; Humans; Research
PubMed: 29845543
DOI: 10.1007/978-981-10-8727-1_23 -
Emerging Microbes & Infections Mar 2017Zika virus (ZIKV) is an emerging RNA virus in the widespread Flavivirus genus. Recently, ZIKV has rapidly spread around the world and has been implicated in human... (Review)
Review
Zika virus (ZIKV) is an emerging RNA virus in the widespread Flavivirus genus. Recently, ZIKV has rapidly spread around the world and has been implicated in human disease, including neurological disorders, triggering public and scientific attention. Understanding how ZIKV causes disease is the highest priority, yet little is known about this virus. Here we examine the currently published data from ZIKV studies to provide the latest understanding of ZIKV genome biology and molecular pathogenesis. The ZIKV genome evolved rapidly from the Flavivirus genus and diverged from the members of this genus, even within the dengue virus cluster to which ZIKV belongs. Genome variations and divergences also exist among ZIKV strains/isolates. These genome divergences might account for the uniqueness of Zika disease. ZIKV infection activates not only the antiviral immune response but also the pro-inflammatory responses associated with disease symptoms. Strikingly, ZIKV activates protein complexes that are functionally associated with disease process, such as glial cell activation and proliferation (for example, Toll-like receptors), apoptosis and cell death, and inflammation. The activation of these complexes may critically contribute to Zika disease. The novel insights into ZIKV genome divergence and disease mechanisms summarized in this review will help accelerate the development of anti-ZIKV strategies.
Topics: Apoptosis; Cell Proliferation; Dengue Virus; Evolution, Molecular; Genetic Variation; Genome, Viral; Humans; Neuroglia; Phylogeny; Zika Virus Infection
PubMed: 28325921
DOI: 10.1038/emi.2016.141 -
PLoS Neglected Tropical Diseases 2015Dengue is one of the most significant public health problems in tropical and subtropical countries, and is increasingly being detected in traditionally non-endemic...
Dengue is one of the most significant public health problems in tropical and subtropical countries, and is increasingly being detected in traditionally non-endemic areas. In Bhutan, dengue virus (DENV) has only recently been detected and limited information is available. In this study, we analyzed the epidemiological and molecular characteristics of DENV in two southern districts in Bhutan from 2013-2014. During this period, 379 patients were clinically diagnosed with suspected dengue, of whom 119 (31.4%) were positive for DENV infection by NS1 ELISA and/or nested RT-PCR. DENV serotypes 1, 2 and 3 were detected with DENV-1 being predominant. Phylogenetic analysis of DENV-1 using envelope gene demonstrated genotype V, closely related to strains from northern India.
Topics: Adolescent; Adult; Aged; Bhutan; Child; Child, Preschool; Dengue; Dengue Virus; Female; Genotype; Humans; Male; Middle Aged; Molecular Epidemiology; Molecular Sequence Data; Phylogeny; Young Adult
PubMed: 26295474
DOI: 10.1371/journal.pntd.0004010 -
Current Opinion in Virology Aug 2020The first licensed dengue vaccine led to considerable controversy, and to date, no dengue vaccine is in widespread use. All three leading dengue vaccine candidates are... (Review)
Review
The first licensed dengue vaccine led to considerable controversy, and to date, no dengue vaccine is in widespread use. All three leading dengue vaccine candidates are live attenuated vaccines, with the main difference between them being the type of backbone and the extent of chimerization. While CYD-TDV (the first licensed dengue vaccine) does not include non-structural proteins of dengue, TAK-003 contains the dengue virus serotype 2 backbone, and the Butantan/Merck vaccine contains three full-genomes of the four dengue virus serotypes. While dengue-primed individuals can already benefit from vaccination against all four serotypes with the first licensed dengue vaccine CYD-TDV, the need for dengue-naive population has not yet been met. To improve tetravalent protection, sequential vaccination should be considered in addition to a heterologous prime-boost approach.
Topics: Animals; Dengue; Dengue Vaccines; Dengue Virus; Drug Development; Humans
PubMed: 33086187
DOI: 10.1016/j.coviro.2020.09.004 -
Epidemiology and Infection Mar 2017We studied the evolution, genotypes, and the molecular clock of dengue virus serotype 1 (DENV-1), between 2001 and 2014 in Guangzhou, China. The analysis of the envelope...
We studied the evolution, genotypes, and the molecular clock of dengue virus serotype 1 (DENV-1), between 2001 and 2014 in Guangzhou, China. The analysis of the envelope (E) gene sequences of 67 DENV-1 strains isolated in Guangzhou, together with 58 representative sequences downloaded from NCBI, have shown shifts in viral genotypes. The genotype changed several times, from genotype I to IV in 2002, from IV to I in 2005, and from I to V in 2014. These genotype shifts may be the cause of DENV outbreaks. The diversity of genotypes and clades demonstrates a high risk of future outbreaks in Guangzhou. The mean rate of virus nucleotide substitution in Guangzhou was determined to be 7·77 × 10-4 per site per year, which represents a medium substitution rate compared to two other countries. Our research can point to different ancestors of the isolated strains, which may further reveal the different origins and transmission of DENV-1 strains in Guangzhou.
Topics: China; Dengue; Dengue Virus; Disease Outbreaks; Evolution, Molecular; Gene Products, env; Genetic Variation; Genotype; Humans; Molecular Epidemiology; Sequence Analysis, DNA
PubMed: 27919298
DOI: 10.1017/S0950268816002429 -
The American Journal of Tropical... Oct 2019The incidence of dengue is increasing in Guangdong, China, with the largest outbreak to date in 2014. Widespread awareness of epidemiological and molecular...
The incidence of dengue is increasing in Guangdong, China, with the largest outbreak to date in 2014. Widespread awareness of epidemiological and molecular characteristics of the dengue virus (DENV) is required. In 2014, we isolated the virus from patients and sequenced its genome. The sequences of DENV isolated from Guangdong and other countries screened since 2005 were studied to establish molecular evolutionary databases along with epidemiological data to explore its epidemiological, phylogenetic, and molecular characteristics. Causes underlying the occurrence of the dengue epidemic included importation and localization of the virus. The number of indigenous cases significantly exceeded that of imported cases. Dengue virus 1 is the most important serotype and caused the long-term epidemic locally. Based on the data available since 2005, DENV1 was divided into three genotypes (I, IV, and V). Only genotypes I and V were detected in 2014. In 2014, an epidemic involving old lineages of DENV1 genotype V occurred after 2 years of silence. The genotype was previously detected from 2009 to 2011. Genotype I, which caused recent epidemics, demonstrated a continuation of new lineages, and a predictive pattern of molecular evolution since 2005 among the four lineages was present. The DENV isolated from Guangdong was closely related to those causing large-scale epidemics in neighboring countries, suggesting the possibility of its import from these countries. The lack of sufficient epidemiological data and evidence on the local mosquito-borne DENV emphasizes the importance of studying the molecular evolutionary features and establishing a well-established phylogenetic tree for dengue prevention and control in Guangdong.
Topics: Dengue Virus; Endoplasmic Reticulum Chaperone BiP; Evolution, Molecular; Genotype; Heat-Shock Proteins; Molecular Docking Simulation; Phylogeny; Protein Conformation; Viral Proteins
PubMed: 31392945
DOI: 10.4269/ajtmh.18-0951