Dengue virus infection and neurological manifestations: an update

Abstract

Dengue virus is a flavivirus transmitted by the mosquitoes, Aedes aegypti and Aedes albopictus. Dengue infection by all four serotypes (DEN 1 to 4) is endemic globally in regions with tropical and sub-tropical climates, with an estimated 100-400 million infections annually. Among those hospitalized, the mortality is about 1%. Neurological involvement has been reported to be about 5%. The spectrum of neurological manifestations spans both the peripheral and central nervous systems. These manifestations could possibly be categorised into those directly related to dengue infection, i.e. acute and chronic encephalitis, indirect complications leading to dengue encephalopathy, and post-infectious syndrome due to immune-mediated reactions, and manifestations with uncertain mechanisms such as acute transverse myelitis, acute cerebellitis, and myositis. The rising trend in global dengue incidence calls for attention to a more explicit definition of each neurological manifestation for more accurate epidemiological data. The actual global burden of dengue infection with neurological manifestation is essential for future planning and execution of strategies, especially in the development of effective antiviral and vaccines against the dengue virus. In this update, we discussed the recent findings of different spectrums of neurological manifestations in dengue infection and provided up-to-date antiviral and vaccine development and its challenges.

Neuro-Ophthalmic Dengue Infection: A Case Report with a Multiple Body Site Sampling Strategy and Review of Laboratory Data

“…Compared with previous studies, prolonged viremia (median of 30 days) is not uncommon in immunocompromised patients [19]. However, such prolonged viraemia (24 days post admission) in an immunocompetent individual is very unusual and is significantly out of proportion to the expected duration, even for a primary infection (ranging from 4 to 14 days) [15]. The exact duration of DENV symptoms in this case was difficult to delineate, due to the concurrent norovirus infection.…”

“…Dengue neurological disease can manifest as encephalitis, encephalopathy, neuroophthalmic involvement, or neuromuscular disorders, reported at a frequency of around 0.5% [1, [11][12][13][14]. Treatment is largely supportive, as the development of effective antivirals has been hindered by a lack of in vivo models that replicate severe dengue infection [15]. The prognosis for neurological disease is variable [9], and predictor for disease development remains elusive.…”

Neurodengue, a narrative review of the literature

“…Encephalopathy is the most frequent CNS complication in DF patients. 3,19 It is defined by a decreased level of consciousness associated or not with seizures and behavioral disturbances. 16 Among 2,441 patients with dengue hemorrhagic fever (DHF) in Thailand, it was present in 6%.…”

“…41 The treatment of GBS associated with DF is the same as the one for GBS due to other causes, with no difference in prognosis. 19 Cranial neuropathies are rare manifestations of acute DF, and the most affected cranial nerves are the 7th, 2nd, 6th, and 3rd. [62][63][64][65][66][67] In some studies, 18,41,68 brachial neuritis (neuralgic amyotrophy), resulting from a presumably immunemediated mechanism, has also been reported with DF.…”

“…Several DENV vaccines are currently being developed and tested in clinical trials. 19,90,96 The two presently-licensed DENV vaccines are Dengvaxia (Sanofi Pasteur, Lyon, France) and Qdenga (TAK-003, Takeda Pharmaceuticals, Tokio, Japan). The primary goal of DENV vaccine development is to generate neutralizing antibodies against each of the four DENV serotypes.…”