Involvement of the central nervous system in patients with dengue virus infection

Domingues, Renan Barros; Kuster, Gustavo W.; Onuki-Castro, Fábio L.; Souza, Vanda Akico Ueda Fick de; Levi, José Eduardo; Pannuti, Cláudio Sérgio

doi:10.1016/j.jns.2007.09.040

Cited by 131 publications

(133 citation statements)

References 18 publications

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“…2 Another study in Viet Nam found that 0.5% of children admitted for dengue hemorrhagic fever (DHF), which is a subset of severe dengue, had serologically confirmed DENV infection with encephalopathy, although rates of dengue-associated neurologic diseases as high as 21% have been reported. 3,4 The most efficient vector for DENV is Aedes aegypti, which is present in limited areas of the southern United States, but its current geographic distribution is not well-documented. 5 Ae.…”

mentioning

confidence: 99%

Surveillance for Dengue and Dengue-Associated Neurologic Syndromes in the United States

Waterman

Margolis

Sejvar

2015

The American Society of Tropical Medicine and Hygiene

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Abstract. Autochthonous dengue virus transmission has occurred in the continental United States with increased frequency during the last decade; the principal vector, Aedes aegypti, has expanded its geographic distribution in the southern United States. Dengue, a potentially fatal arboviral disease, is underreported, and US clinicians encountering patients with acute febrile illness consistent with dengue are likely to not be fully familiar with dengue diagnosis and management. Recently, investigators suggested that an outbreak of dengue likely occurred in Houston during 2003 based on retrospective laboratory testing of hospitalized cases with encephalitis and aseptic meningitis. Although certain aspects of the Houston testing results and argument for local transmission are doubtful, the report highlights the importance of prospective surveillance for dengue in Aedes-infested areas of the United States, the need for clinical training on dengue and its severe manifestations, and the need for laboratory testing in domestic patients presenting with febrile neurologic illness in these regions to include dengue.Dengue is an arboviral disease of major public health significance caused by four serologically related flaviviruses, dengue viruses (DENVs 1-4), with an expanding worldwide distribution.1 Although many DENV infections are asymptomatic, classic clinical dengue manifests as an acute febrile illness, with symptoms that include headache, retro-orbital pain, myalgia, arthralgia, and rash. Clinical dengue is usually a self-limited illness of about 1 week's duration, but severe illness can occur in both healthy persons and those with other underlying diseases. A relatively small percentage (approximately 10%) of persons with clinical dengue progresses to severe disease because of plasma leakage, which can lead to decompensated shock and death if not carefully managed with appropriate fluid therapy. Most patients requiring hospitalization for dengue have severe disease or complications related to underlying comorbid disease. DENVs seem to be less neurotropic than other flaviviruses, such as West Nile virus, St. Louis encephalitis virus, and Japanese encephalitis virus. DENV-associated neurologic disease, including neuroinvasive disease, has been rarely documented by isolation of virus and detection of DENV-specific immunoglobulin M (IgM) antibody in cerebrospinal fluid (CSF) or brain tissue. In Viet Nam, about 1% of patient hospitalizations with suspected dengue had encephalitis or aseptic meningitis syndromes. 2Another study in Viet Nam found that 0.5% of children admitted for dengue hemorrhagic fever (DHF), which is a subset of severe dengue, had serologically confirmed DENV infection with encephalopathy, although rates of dengue-associated neurologic diseases as high as 21% have been reported. 3,4The most efficient vector for DENV is Aedes aegypti, which is present in limited areas of the southern United States, but its current geographic distribution is not well-documented. Ae. albopictus is a less efficient tran...

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mentioning

confidence: 99%

Surveillance for Dengue and Dengue-Associated Neurologic Syndromes in the United States

Waterman

Margolis

Sejvar

2015

The American Society of Tropical Medicine and Hygiene

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“…As recently reported by Domingues et al, the most frequent manifestation of CNS involvement in acute dengue virus infection is mental confusion as part of diffuse encephalitis, usually with good prognosis [50]. It is still unclear whether such manifestations result from metabolic imbalance, immune-mediated tissue damage or direct viral invasion of the CNS [50]. The same authors have demonstrated that dengue virus may actively invade the CNS during acute infection, but it is uncertain whether this process is responsible for symptoms [50].…”

Section: Arthropod-borne Viral Encephalitismentioning

confidence: 71%

“…There are not many systematic studies of neuroimaging findings in dengue CNS involvement. Routine CSF analysis is usually unrevealing, but may disclose mild pleocytosis [50]. As described in the study of Domingues et al, the CSF viral load is very low and therefore nucleic acids are usually not detected in CSF samples [50].…”

Section: Arthropod-borne Viral Encephalitismentioning

confidence: 99%

“…The involvement of CNS in dengue infection has been reported, but its frequency has not been established yet [41][42][43][44][45][46][47][48][49]. As recently reported by Domingues et al, the most frequent manifestation of CNS involvement in acute dengue virus infection is mental confusion as part of diffuse encephalitis, usually with good prognosis [50]. It is still unclear whether such manifestations result from metabolic imbalance, immune-mediated tissue damage or direct viral invasion of the CNS [50].…”

Section: Arthropod-borne Viral Encephalitismentioning

confidence: 99%

“…It is still unclear whether such manifestations result from metabolic imbalance, immune-mediated tissue damage or direct viral invasion of the CNS [50]. The same authors have demonstrated that dengue virus may actively invade the CNS during acute infection, but it is uncertain whether this process is responsible for symptoms [50]. The diagnosis of this infection relies on epidemiological data and specific laboratory tests including antibodies, antigens or nucleic acids detection [51].…”

Section: Arthropod-borne Viral Encephalitismentioning

confidence: 99%

See 2 more Smart Citations

Management of acute viral encephalitis in Brazil

Domingues

Teixeira

2009

Braz J Infect Dis

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Chronic Dengue Virus Panencephalitis in a Patient with Progressive Dementia with Extrapyramidal Features

Johnson

Larman

Lee

et al. 2019

Annals of Neurology

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Objective: To determine the underlying etiology in a patient with progressive dementia with extrapyramidal signs and chronic inflammation referred to the National Institutes of Health Undiagnosed Diseases Program. Methods: Extensive investigations included metabolic profile, autoantibody panel, infectious etiologies, genetic screening, whole exome sequencing, and the phage-display assay, VirScan, for viral immune responses. An etiological diagnosis was established postmortem. Results: Using VirScan, enrichment of dengue viral antibodies was detected in cerebrospinal fluid as compared to serum. No virus was detected in serum or cerebrospinal fluid, but postmortem analysis confirmed dengue virus in the brain by immunohistochemistry, in situ hybridization, quantitative polymerase chain reaction, and sequencing. Dengue virus was also detectable by polymerase chain reaction and sequencing from brain biopsy tissue collected 33 months antemortem, confirming a chronic infection despite a robust immune response directed against the virus. Immunoprofiling and whole exome sequencing of the patient did not reveal any immunodeficiency, and sequencing of the virus demonstrated wild-type dengue virus in the central nervous system. Interpretation: Dengue virus is the most common arbovirus worldwide and represents a significant public health concern. Infections with dengue virus are usually self-limiting, and chronic dengue infections have not been previously reported. Our findings suggest that dengue virus infections may persist in the central nervous system causing a panencephalitis and should be considered in patients with progressive dementia with extrapyramidal features in endemic regions or with relevant travel history. Furthermore, this work highlights the utility of comprehensive antibody profiling assays to aid in the diagnosis of encephalitis of unknown etiology.

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Involvement of the central nervous system in patients with dengue virus infection

Cited by 131 publications

References 18 publications

Surveillance for Dengue and Dengue-Associated Neurologic Syndromes in the United States

Surveillance for Dengue and Dengue-Associated Neurologic Syndromes in the United States

Management of acute viral encephalitis in Brazil

Chronic Dengue Virus Panencephalitis in a Patient with Progressive Dementia with Extrapyramidal Features

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