Autoimmune pathogenesis in dengue virus infection viral. Dengue virus denv belongs to the family flaviviridae, genus flavivirus, and is transmitted to humans by aedes mosquitoes, mainly aedes aegypti. Transmission occurs through the bite of infected aedes mosquitoes, principally aedes aegypti, which is also the principal urban vector of yellow fever. Rebeca ricohesses laboratory is studying the structural rna andor protein and transmission replication in aedes aegypti characteristics of dengue type 2 and type 3 virus variants that have produced dengue hemorrhagic fever in humans throughout the world. The most widely cited hypothesis for this occurrence is antibody dependent enhancement ade of disease. Recent insights into the disease have driven the development of vaccines and therapeutics. The clec5adv interaction is critical for dvinduced hemorrhagic fever and shock syndrome, so the sensing of clec5adv binding is crucial to realize a thorough study of the pathogenesis of dengue. Pdf the dengue virus can infect many cell types and cause diverse clinical and pathological effects.
Dengue pathogenesis, clinical manifestation, lab diagnosis and treatment pathogenesis of dengue. Pathogenesis of dhfstep 1 homologous antibodies form non infectious complexes 1 1 1 1 dengue 1 virus neutralizing antibody to dengue 1 virus nonneutralizing antibody 1 complex formed by neutralizing antibody and virus. The high mutability of rna viruses such as flaviviruses leads to a. Generally, dengue is classified as a blood infection and the. Molecular insight into dengue virus pathogenesis and its implications for disease control. Plasma leakage and intrinsic coagulopathy are the pathological hall marks in dengue haemorrhagic fever dhf. Dengue virus denv infections of humans were long thought to be selflimited and of low mortality.
Dengue viral infections postgraduate medical journal. Molecular insight into dengue virus pathogenesis and its. More than 50 years of research on dengue has resulted in a host of literature, which strongly suggests that the pathogenesis of dhf and dss involves viral. Dengue fever is an infectious disease carried by mosquitoes and caused by any of four related dengue viruses. They may be asymptomatic or may give rise to undifferentiated fever, dengue fever, dengue haemorrhagic fever dhf, or dengue shock syndrome.
The clinical manifestations of dengue are the expression of a constellation of host and viral factors, some acquired, others intrinsic to the individual. Pathogenesis of liver involvement during dengue viral. Zika virus pathogenesis in rhesus macaques is unaffected. Monocytes are involved in dengue viral disease, however, their exact role is still not clear. Dengue proteins with their role in pathogenesis, and.
Dengue is an arboviral disease caused by dengue virus. All of these loci intervene in viral replication via complex virusvirus and virushost. Pdf dengue viral infections are one of the most important mosquito borne viral infections in the world. Much remains to be learned about the pathogenesis of the different manifestations of dengue virus denv infections in humans. Pathogenesis of dengue haemorrhagic fever and its impact. Substantial gaps remain in the comprehensive understanding of the pathogenesis of dengue virus infections. Dengue virus is an arbovirus belonging to class flaviviridae its clinical manifestation ranges from asymptomatic to extreme conditions dengue hemorrhagic feverdengue shock syndrome. Role of monocytes in the pathogenesis of dengue springerlink. Pdf pathogenesis of dengue viral infections researchgate. Zikv is a positivesense singlestranded enveloped rna virus. In large part, this limitation is related to the lack of a suitable animal model of disease. Understanding the pathogenesis of dhfdss has been hampered by the lack of in vitro and in vivo models of the disease. Rhesus monkeys develop viremia similar in pattern to humans after dengue virus challenge but do not develop clinical disease.
They are rna viruses that belong to the flavivirus genusflaviviridae family, which also includes the yellow fever virus, west nile virus, japanese encephalitis virus, zika virus, and the st louis encephalitis virus. Here we investigate the immunoglobulin responses of patients with dengue fever df and. The role of ns1specific antibodies in the pathogenesis of dengue virus infection is poorly understood. Severe dengue most commonly occurs among infants and patients with secondary dengue virus denv infections i. Pdf dengue virus denv infections of humans were long thought to be self limited and of low mortality. Dengue hemorrhagic fever can occur when someone is bitten by a mosquito or exposed to blood infected with the dengue virus. Beginning in the 1950s, at the time when four different denvs were discovered, a lethal variant of dengue emerged. It is transmitted by mosquitoes of the genus aedes, which are widely distributed in subtropical and tropical areas of the world see the image below. These viruses generally cause a benign syndrome, dengue fever, in the american and african tropics, and a severe syndrome, dengue hemorrhagic feverdengue shock syndrome dhfdss, in southeast asian children.
The dengue virus nonstructural1 protein ns1 generates antibodies to common epitopes on human blood clotting, integrinadhesin proteins and binds to human endothelial cells. Secondary infection by a different dengue virus serotype has been confirmed as an important risk factor for the development of dhf. Management of dengue fever outpatient triageno hemorrhagic manifestations and patient iswellhydrated. Dengue viruses occur as four antigenically related but distinct serotypes transmitted to humans by aedes aegypti mosquitoes. Dengue hemorrhagic feverdengue shock syndrome dhfdss initially observed in southeast asia now has spread throughout the world. The aetiology and longterm history of dengue disease are well known. So what are the factors associated with the occurrence of dhf. Dengue, dengue fever df, dengue hemorrhagic fever dhf, dengue shock syndrome dss s new who classification categorizes dengue into dengue, with and without warning signs, and severe. Dengue virus produces a mild acute febrile illness, dengue fever df and a severe illness, dengue hemorrhagic fever dhf. Patients with dhfdss are characterized by several manifestations, including severe thrombocytopenia, vascular leakage, and. Diseases caused by dengue virus denv are a major public health problem worldwide, considered one of the infections with more prevalence in tropical and subtropical zones of the world. Although the exact mechanisms are not clear, ade is the process in which denv, complexed with nonneutralizing antibodies, can enter a greater proportion of cells of the mononuclear lineage, thus increasing virus production. As both cell tropism and tissue tropism of denv are considered major determinants in the pathogenesis of. The incidence of dengue has increased dramatically in recent decades, with estimates of 40%50% of the worlds population at risk for the.
The who estimates that 50100 million cases of dengue infection occur annually, with approximately 500,000 of those cases resulting in dengue hemorrhagic fever dhf, with an estimated 22,000 deaths per year, mostly in children. Symptomatic dengue infection causes a wide range of clinical manifestations, from mild dengue fever df to potentially fatal disease, such as dengue hemorrhagic fever dhf or dengue shock syndrome dss. Introduction dengue and dengue hemorrhagic fever dhf result from infection by any of four serotypes of dengue viruses. Dhf can occur in primary infection with certain genetic strains of. The pathogenic mechanisms of dengue hemorrhagic fever and dengue shock syndrome dhfdss caused by dengue virus dv infection remain unresolved.
Pdf dengue virus denv infections of humans were long thought to be selflimited and of low mortality. Progress towards understanding the pathogenesis of dengue. This disease used to be called breakbone fever because it sometimes causes severe joint and muscle pain that feels like bones are breaking. Pathogenesis of liver involvement during dengue viral infections. These may include a high fever, headache, vomiting, muscle and joint pains, and a characteristic skin rash. Dengue viral infections are one of the most important mosquito borne diseases in the world. In recent years, dhf epidemics have intensified and become a major cause of morbidity. Mortality from severe dengue is low, but the economic and resource burden on health services remains substantial in endemic settings. Pathogenesis of vascular leak in dengue virus infection. Pathogenesis and pathophysiology of dengue hemorrhagic fever. Symptoms typically begin three to fourteen days after infection. Zika virus zikv is an arthropodborne flavivirus in the family flaviviridae, which includes several other arthropodborne viruses of clinical importance, such as dengue virus denv, west nile virus wnv, and yellow fever virus yfv. Spak spak dengue virus family flaviviridae genus flavivirus enveloped, single strand rna viruses genomic rna 11 kb and encodes 3 structural proteins.
Infected local cells then migrate from site of infection to lymph nodes, where monocytes and macrophages are recruited, which become targets of infection. Dengue fever is a reemerging viral disease and affects millions of population worldwide. Based on neutralization assay data, four serotypes denv1, denv2, denv3, and denv4 can be distinguished. They may range from subclinical infection to dengue fever, dengue hemorrhagic fever dhf, and eventually dengue shock syndrome dss. For patients presenting during the first week after fever onset, diagnostic testing should include a test for dengue virus rtpcr or ns1 and igm figure 401. For patients presenting 1 week after fever onset, an igm test is most useful. Viral virulence, infection enhancing antibodies, cytokines and chemical mediators in the setting of intense immune activation are the key players implicated in the pathogenesis of dhf. Dengue virus infects nearly 400 million humans each year. Dengue is an important cause of childhood and adult morbidity in asian and latin american countries and its geographic footprint is growing. The most widelycited hypothesis for the pathogenesis of severe dengue is antibodydependent enhancement ade. Despite the intense research in the pathogenesis of denv, this feature is not well understood.
Role of ns1 antibodies in the pathogenesis of acute. Pdf autoimmune pathogenesis in dengue virus infection. Dengue is the most common and important arthropodborne viral arboviral illness in humans. Dengue fever is a mosquitoborne tropical disease caused by the dengue virus.
Infection may be asymptomatic or present with a broad range of clinical manifestations including a mild febrile illness to a lifethreatening shock syndrome. A lot of research has been done on this ailment, yet there is. Health experts have known about dengue fever for more than 200 years. Pathogenesis of dengue viral infections sri lankan journal of. Pathogenesis of dhfdss risk factors reported for dhf most cases of dengue fever are selflimited in their course and never progress to dengue hemorrhagic fever. There are four dengue virus serotypes den14 which are closely related. This type of antibody is found in secondary infection and described in pathogenesis of severe dengue fever like dengue hemorrhagic fever dhf and dengue shock syndrome dss. Dengue is a mosquitoborne disease caused by infection with dengue virus denv that represents a serious and expanding global health threat.
As both cell tropism and tissue tropism of denv are considered major determinants in the pathogenesis of dengue, there is a critical need for adequate tropism assays, animal models, and human autopsy data. Even during secondary infection, severe dengue is relatively rare, with only 0. Dengue chapter 4 2020 yellow book travelers health. Focusing on the pathogenesis of dengue, a pattern of acute viral infection can be seen. Dengue virus after entering in the body invades the local macrophages and multiply there. Dengue dengue hemorrhagic hemorrhagic fever fever pathogenesis and pathophysiology alan alan r. Dengue pathogenesis, clinical manifestation, lab diagnosis. Unfortunately, progress towards development of effective therapeutics has been slow, despite notable advances in the understanding of disease pathogenesis and considerable investment in antiviral drug discovery. Dengue is a febrile illness caused by infection with one of four dengue viruses denv transmitted by aedes aegypti or aedes albopictus mosquitoes during the taking of a blood meal. In the secondary infection with different dengue serotype, tcell cannot inhibit viral infection completely. Dengue infection is caused by 4 antigenically distinct dengue virus serotypes. Life cycle of the dengue fever virus hhmi biointeractive video. The most widely cited hypothesis for this occurrence is antibody dependent enhancement ade of. World health organization, regional office for southeast asia.
Since the second edition of dengue haemorrhagic fever. Dengue fever breakbone fever dengue virus, transmitted mainly by aedes aegypti endemic in the caribbean, central and south america, africa and southeast asia billions at risk 400 million infectionsyear second only to malaria among insectborne diseases virology lectures 2017 prof. Although infection with the dengue virus denv is associated with a self. Annually, 100 million cases of dengue fever and half a million cases of dhf occur worldwide. The characteristic feature of dhf is increased capillary permeability leading to extensive plasma leakage in serous cavities resulting in shock. Dengue virus denv is a member of the flavivirus genus of sin glestranded positivesense rna. The dengue virus is a single stranded rna virus belonging to the flaviviridae family. Ninety percent of dhf subjects are children less than 15. Zika virus zikv is a reemerging virus that has recently spread into dengue virus denv endemic regions and crossreactive antibodies abs could potentially affect zikv pathogenesis. Questions on viral population biology to complete dengue puzzle. Initial infection with a particular serotype is known as primary infection, which is usually.
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