Zika virus pathogenesis in rhesus macaques is unaffected. Dengue infection is caused by 4 antigenically distinct dengue virus serotypes. Pdf dengue virus denv infections of humans were long thought to be selflimited and of low mortality. Dengue virus denv infections of humans were long thought to be selflimited and of low mortality. For patients presenting 1 week after fever onset, an igm test is most useful. Pathogenesis and pathophysiology of dengue hemorrhagic fever. 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. One of the main target cells for denv infection is monocytes. 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. The aetiology and longterm history of dengue disease are well known. Molecular insight into dengue virus pathogenesis and its.
The high mutability of rna viruses such as flaviviruses leads to a. The dengue virus is a single stranded rna virus belonging to the flaviviridae family. 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. Severe dengue most commonly occurs among infants and patients with secondary dengue virus denv infections i. Dengue dengue hemorrhagic hemorrhagic fever fever pathogenesis and pathophysiology alan alan r. Patients with dhfdss are characterized by several manifestations, including severe thrombocytopenia, vascular leakage, and. Dengue virus after entering in the body invades the local macrophages and multiply there. Annually, 100 million cases of dengue fever and half a million cases of dhf occur worldwide.
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. Despite the intense research in the pathogenesis of denv, this feature is not well understood. Understanding the pathogenesis of dhfdss has been hampered by the lack of in vitro and in vivo models of the disease. As both cell tropism and tissue tropism of denv are considered major determinants in the pathogenesis of. There are four dengue virus serotypes den14 which are closely related. The characteristic feature of dhf is increased capillary permeability leading to extensive plasma leakage in serous cavities resulting in shock. Mortality from severe dengue is low, but the economic and resource burden on health services remains substantial in endemic settings. Even during secondary infection, severe dengue is relatively rare, with only 0.
The role of ns1specific antibodies in the pathogenesis of dengue virus infection is poorly understood. Symptoms typically begin three to fourteen days after infection. 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. Much remains to be learned about the pathogenesis of the different manifestations of dengue virus denv infections in humans. 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. The most widelycited hypothesis for the pathogenesis of severe dengue is antibodydependent enhancement ade. 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. A lot of research has been done on this ailment, yet there is. Monocytes are involved in dengue viral disease, however, their exact role is still not clear. Substantial gaps remain in the comprehensive understanding of the pathogenesis of dengue virus infections. All of these loci intervene in viral replication via complex virusvirus and virushost. Dengue virus denv is a member of the flavivirus genus of sin glestranded positivesense rna.
Transmission occurs through the bite of infected aedes mosquitoes, principally aedes aegypti, which is also the principal urban vector of yellow fever. 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. The dengue virus nonstructural1 protein ns1 generates antibodies to common epitopes on human blood clotting, integrinadhesin proteins and binds to human endothelial cells. Dengue is an important cause of childhood and adult morbidity in asian and latin american countries and its geographic footprint is growing. The incidence of dengue has increased dramatically in recent decades, with estimates of 40%50% of the worlds population at risk for the. Initial infection with a particular serotype is known as primary infection, which is usually. Pathogenesis of dengue haemorrhagic fever and its impact.
Management of dengue fever outpatient triageno hemorrhagic manifestations and patient iswellhydrated. In large part, this limitation is related to the lack of a suitable animal model of 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. Dengue virus produces a mild acute febrile illness, dengue fever df and a severe illness, dengue hemorrhagic fever dhf. World health organization, regional office for southeast asia. Dengue pathogenesis, clinical manifestation, lab diagnosis. They may be asymptomatic or may give rise to undifferentiated fever, dengue fever, dengue haemorrhagic fever dhf, or dengue shock syndrome. Pdf autoimmune pathogenesis in dengue virus infection. Dengue fever is an infectious disease carried by mosquitoes and caused by any of four related dengue viruses. Plasma leakage and intrinsic coagulopathy are the pathological hall marks in dengue haemorrhagic fever dhf. This disease used to be called breakbone fever because it sometimes causes severe joint and muscle pain that feels like bones are breaking. In the secondary infection with different dengue serotype, tcell cannot inhibit viral infection completely. Dengue hemorrhagic feverdengue shock syndrome dhfdss initially observed in southeast asia now has spread throughout the world. 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.
Introduction dengue and dengue hemorrhagic fever dhf result from infection by any of four serotypes of dengue viruses. 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. Infected local cells then migrate from site of infection to lymph nodes, where monocytes and macrophages are recruited, which become targets of infection. Rhesus monkeys develop viremia similar in pattern to humans after dengue virus challenge but do not develop clinical disease. Although infection with the dengue virus denv is associated with a self. 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. Pdf the dengue virus can infect many cell types and cause diverse clinical and pathological effects. Since the second edition of dengue haemorrhagic fever.
Dengue virus denv belongs to the family flaviviridae, genus flavivirus, and is transmitted to humans by aedes mosquitoes, mainly aedes aegypti. In recent years, dhf epidemics have intensified and become a major cause of morbidity. Dengue is an arboviral disease caused by dengue virus. Generally, dengue is classified as a blood infection and the. Life cycle of the dengue fever virus hhmi biointeractive video. Focusing on the pathogenesis of dengue, a pattern of acute viral infection can be seen. The most widely cited hypothesis for this occurrence is antibody dependent enhancement ade of disease.
Pathogenesis of liver involvement during dengue viral. Pathogenesis of dengue viral infections sri lankan journal of. The clinical manifestations of dengue are the expression of a constellation of host and viral factors, some acquired, others intrinsic to the individual. 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. Dengue viral infections are one of the most important mosquito borne diseases in the world. 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. Molecular insight into dengue virus pathogenesis and its implications for disease control. The most widely cited hypothesis for this occurrence is antibody dependent enhancement ade of. Pdf pathogenesis of dengue viral infections researchgate. Recent insights into the disease have driven the development of vaccines and therapeutics. Based on neutralization assay data, four serotypes denv1, denv2, denv3, and denv4 can be distinguished.
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. They may range from subclinical infection to dengue fever, dengue hemorrhagic fever dhf, and eventually dengue shock syndrome dss. Questions on viral population biology to complete dengue puzzle. Dengue viruses occur as four antigenically related but distinct serotypes transmitted to humans by aedes aegypti mosquitoes. 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. Dengue fever is a mosquitoborne tropical disease caused by the dengue virus. These may include a high fever, headache, vomiting, muscle and joint pains, and a characteristic skin rash.
Dengue is a mosquitoborne disease caused by infection with dengue virus denv that represents a serious and expanding global health threat. So what are the factors associated with the occurrence of dhf. Dengue pathogenesis, clinical manifestation, lab diagnosis and treatment pathogenesis of dengue. Role of monocytes in the pathogenesis of dengue springerlink. Ninety percent of dhf subjects are children less than 15. Zikv is a positivesense singlestranded enveloped rna virus. The pathogenic mechanisms of dengue hemorrhagic fever and dengue shock syndrome dhfdss caused by dengue virus dv infection remain unresolved. Dengue fever is a reemerging viral disease and affects millions of population worldwide. Dengue proteins with their role in pathogenesis, and. Infection may be asymptomatic or present with a broad range of clinical manifestations including a mild febrile illness to a lifethreatening shock syndrome. Health experts have known about dengue fever for more than 200 years.
Here we investigate the immunoglobulin responses of patients with dengue fever df and. Pathogenesis of liver involvement during dengue viral infections. Autoimmune pathogenesis in dengue virus infection viral. Pathogenesis of vascular leak in dengue virus infection. Role of ns1 antibodies in the pathogenesis of acute. 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 virus infects nearly 400 million humans each year.
Secondary infection by a different dengue virus serotype has been confirmed as an important risk factor for the development of dhf. Beginning in the 1950s, at the time when four different denvs were discovered, a lethal variant of dengue emerged. Denv infection results in a broad spectrum of clinical symptoms, ranging from mild fever to dengue hemorrhagic fever dhf, the latter of which. 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. Dengue virus is an arbovirus belonging to class flaviviridae its clinical manifestation ranges from asymptomatic to extreme conditions dengue hemorrhagic feverdengue shock syndrome. 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 is the most common and important arthropodborne viral arboviral illness in humans. 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. 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. 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. Spak spak dengue virus family flaviviridae genus flavivirus enveloped, single strand rna viruses genomic rna 11 kb and encodes 3 structural proteins. 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.
Progress towards understanding the pathogenesis of dengue. Dhf can occur in primary infection with certain genetic strains of. Dengue viral infections postgraduate medical journal. Pdf dengue viral infections are one of the most important mosquito borne viral infections in the world. Dengue chapter 4 2020 yellow book travelers health.
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