Dengue encephalitis–A rare manifestation of dengue fever

Madi, Deepak; Achappa, Basavaprabhu; Ramapuram, John T; Chowta, Nithyananda K; Laxman, M.; Mahalingam, Soundarya

doi:10.12980/apjtb.4.2014c1006

Cited by 43 publications

(44 citation statements)

References 11 publications

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“…Treatment with compound 10 reduced DENV-2 loads in several organs of mice, including the central nervous system (CNS), and ameliorated tissue damage due to infection. DENV is not classically considered a neurotropic virus, but it may cause encephalitis in humans (31,32) and in immunosuppressed mice, including A129 Ϫ/Ϫ and AG129 Ϫ/Ϫ mice. Here we demonstrated that compound 10 was also able to prevent DENV dissemination to and replication in the CNS of A129 mice, suggesting that this compound may cross the blood-brain barrier.…”

Section: Zandi Et Al Antimicrobial Agents and Chemotherapymentioning

confidence: 99%

Nucleoside Analogs with Selective Antiviral Activity against Dengue Fever and Japanese Encephalitis Viruses

Zandi

Bassit

Amblard

et al. 2019

Antimicrob Agents Chemother

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Dengue virus (DENV) and Japanese encephalitis virus (JEV) are important arthropod-borne viruses from the Flaviviridae family. DENV is a global public health problem with significant social and economic impacts, especially in tropical and subtropical areas. JEV is a neurotropic arbovirus endemic to east and southeast Asia. There are no U.S. FDA-approved antiviral drugs available to treat or to prevent DENV and JEV infections, leaving nearly one-third of the world's population at risk for infection. Therefore, it is crucial to discover potent antiviral agents against these viruses. Nucleoside analogs, as a class, are widely used for the treatment of viral infections. In this study, we discovered nucleoside analogs that possess potent and selective anti-JEV and anti-DENV activities across all serotypes in cell-based assay systems. Both viruses were susceptible to sugar-substituted 2=-C-methyl analogs with either cytosine or 7-deaza-7-fluoro-adenine nucleobases. Mouse studies confirmed the anti-DENV activity of these nucleoside analogs. Molecular models were assembled for DENV serotype 2 (DENV-2) and JEV RNA-dependent RNA polymerase replication complexes bound to nucleotide inhibitors. These models show similarities between JEV and DENV-2, which recognize the same nucleotide inhibitors. Collectively, our findings provide promising compounds and a structural rationale for the development of direct-acting antiviral agents with dual activity against JEV and DENV infections.KEYWORDS Dengue virus, Japanese encephalitis virus, antiviral agents, nucleoside analogs D engue virus (DENV) and Japanese encephalitis virus (JEV) are members of the genus Flavivirus, belonging to the family Flaviviridae. Many flaviviruses are arthropod borne and cause severe infections in humans and vertebrate animals. DENV has four serotypes (DENV-1 to DENV-4), which collectively pose a health threat to 2.5 billion people worldwide, with 50 million to 100 million human infections and 500,000 cases of dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) annually (1-3). JEV is one of the most important neurotropic flaviviruses that causes encephalitis in humans. Symptoms range from mild febrile illness to mortal illness, especially in children, with about 67,900 cases each year (4). JEV is endemic in eastern and southern Asia (including China, Indonesia, Nepal, Thailand, Saipan Island, Pakistan, and the Torres Strait) and Australia, with fatality rates of 20% to 30% and life-long neurological impairments and sequelae among one-half of the survivors (5-8). Despite a licensed vaccine to prevent JEV infection, infections occur annually due to a lack of complete coverage and access (9). A tetravalent DENV vaccine also exists but remains partially on July 10, 2020 by guest http://aac.asm.org/ Downloaded fromArg474. The triphosphate group forms electrostatic interactions with Arg474, Lys694, and two active site Mn 2ϩ ions.Nucleoside inhibitors of DENV. The same 14 nucleoside analogs were assayed against DENV using a BHK-21 cell line harboring the...

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Section: Zandi Et Al Antimicrobial Agents and Chemotherapymentioning

confidence: 99%

Nucleoside Analogs with Selective Antiviral Activity against Dengue Fever and Japanese Encephalitis Viruses

Zandi

Bassit

Amblard

et al. 2019

Antimicrob Agents Chemother

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“…Dengue hemorrhagic fever (DHF) results from secondary infection and is characterized by a recurrent high fever with vascular leak causing widespread bleeding and multisystem disorder. Presentations of CNS disorder were therefore initially attributed to DHF; however, recent studies indicate that patients with DHF infection may present with acute encephalitis, GBS, and polyradiculopathy, and that DENV is directly neurotropic [68][69][70][71].…”

Section: Flaviviridaementioning

confidence: 99%

Encephalitic Arboviruses: Emergence, Clinical Presentation, and Neuropathogenesis

2016

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Arboviruses are arthropod-borne viruses that exhibit worldwide distribution, contributing to systemic and neurologic infections in a variety of geographical locations. Arboviruses are transmitted to vertebral hosts during blood feedings by mosquitoes, ticks, biting flies, mites, and nits. While the majority of arboviral infections do not lead to neuroinvasive forms of disease, they are among the most severe infectious risks to the health of the human central nervous system. The neurologic diseases caused by arboviruses include meningitis, encephalitis, myelitis, encephalomyelitis, neuritis, and myositis in which virus-and immune-mediated injury may lead to severe, persisting neurologic deficits or death. Here we will review the major families of emerging arboviruses that cause neurologic infections, their neuropathogenesis and host neuroimmunologic responses, and current strategies for treatment and prevention of neurologic infections they cause.

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“…5 The rare neurologic presentations reported with DENV infection are transverse myelitis, acute encephalomyelitis, myositis, and Gullain Barre syndrome. 6 The exact pathophysiology of how DENV acts on the nervous system is not clear. It is suggested that neurological symptoms are secondary to systemic manifestation i.e.…”

Section: Discussionmentioning

confidence: 99%

Fatal dengue encephalitis in a recruit: lessons learnt

Pardal¹,

Singh²,

Rath³

et al. 2020

Int J Community Med Public Health

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Dengue infections may present within a widely variable spectrum of clinical manifestations. However, neurologic complications in general are rare and unusual. A 19 yrs old healthy male army recruit was brought to a service hospital in South India in a state of unresponsiveness, following 12 km route march. Despite aggressive and prompt management, his condition progressively deteriorated and he finally passed away about 10 hrs after reporting to the hospital. The final cause of death was acute dengue encephalitis with raised intracranial pressure. Epidemio-clinico-pathological correlation in this case led to the conclusion that vigorous exertion with a hyper-metabolic state of fever in a setting of encephalitis led to metabolic injury, multi-organ failure, cerebral edema and intracranial hemorrhage. Encephalitis following dengue virus (DENV) infection is a rare phenomenon with the incidence ranging from 0.5% to 6.2%. Neurological features associated with DENV were first reported by Sanguansermsri et al in 1976. The rare neurologic presentations reported with DENV infection are transverse myelitis, acute encephalomyelitis, myositis, and gullain barre syndrome. As encephalitis caused by DENV mimics that caused by other pathogens it should always be kept in mind while managing encephalitis of unknown origin. Medical officers should maintain a high index of suspicion of DENV encephalitis. Training of medical officers; therefore, needs to be undertaken with regular refresher cadres, besides equipping of all peripheral facilities with rapid diagnostic kits for dengue. The same will ensure prompt detection of cases and timely referral to higher medical centres in chain. The instant case reflects an important, potentially fatal, complication of dengue. Pathophysiology of DENV encephalitis needs to be elucidated on priority through research involving all stakeholders.

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Dengue encephalitis–A rare manifestation of dengue fever

Cited by 43 publications

References 11 publications

Nucleoside Analogs with Selective Antiviral Activity against Dengue Fever and Japanese Encephalitis Viruses

Nucleoside Analogs with Selective Antiviral Activity against Dengue Fever and Japanese Encephalitis Viruses

Encephalitic Arboviruses: Emergence, Clinical Presentation, and Neuropathogenesis

Fatal dengue encephalitis in a recruit: lessons learnt

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