Complete genome analysis and characterization of neurotropic dengue virus 2 cosmopolitan genotype isolated from the cerebrospinal fluid of encephalitis patients

Tun, Mya Myat Ngwe; Muthugala, Rohitha; Nabeshima, Takeshi; Soe, Aung Min; Dumre, Shyam Prakash; Rajamanthri, Lakmali; Jayawardana, Dulani; Attanayake, Shanthi; Inoue, Satoshi; Morita, Kouichi

doi:10.1371/journal.pone.0234508

Cited by 19 publications

(23 citation statements)

References 47 publications

(56 reference statements)

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“…Another possible mechanism is a direct CNS invasion by the dengue virus through the compromised blood-brain barrier. The direct neurotropism of the dengue virus has recently been illustrated with the isolation of the virus RNA in the CSF, also evidenced in our case report [ 16 ].…”

Section: Discussionsupporting

confidence: 62%

A Rare Case of Dengue Encephalitis with Raised Procalcitonin

Nadarajan

Toh

2021

Am J Case Rep

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Patient: Male, 65-year-old Final Diagnosis: Dengue encephalitis Symptoms: AMS Medication:— Clinical Procedure: — Specialty: Infectious Diseases Objective: Rare co-existance of disease or pathology Background: Dengue virus is a common arbovirus with uncertain neurotropism. Dengue encephalitis is a rare but fatal manifestation of severe dengue. Diagnosis requires high clinical suspicion. It should be routinely considered in patients with encephalopathy, especially in countries where dengue virus is endemic. Unlike other forms of severe dengue, the typical warning signs and biochemical derangements are not reliable markers for dengue encephalitis. Alternative biochemical markers of dengue encephalitis are needed. Case Report: We present a case of dengue encephalitis with distinctly raised procalcitonin (13.2 μg/L), in the absence of the typical warning signs and biochemical derangements of severe dengue. The patient was a 65-year-old man with fever and sudden loss of consciousness in the absence of other localizing signs/symptoms. Inflammatory markers were raised, with findings of leptomeningeal enhancement on brain computed tomography suggestive of meningoencephalitis. Septic workup was unremarkable (normal renal and liver functions, negative blood and urine cultures). The typical neurotropic microorganisms were not detected in the cerebrospinal fluid. On day 4 of admission, the patient reported abdominal pain and hematuria with a new onset of bicytopenia. Subsequent investigations for dengue infection were positive for serum dengue NS1 antigen and dengue RNA (type 2 strain) in cerebrospinal fluid, confirming the diagnosis of dengue encephalitis. The patient was managed supportively and experienced full clinical recovery. Conclusions: Dengue encephalitis is a rare condition with nonspecific biochemical and imaging abnormalities. We demonstrated that a raised procalcitonin level can occur in the setting of dengue encephalitis. In endemic countries, this finding may prompt further investigations for dengue encephalitis in patients with meningoencephalitis.

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Section: Discussionsupporting

confidence: 62%

A Rare Case of Dengue Encephalitis with Raised Procalcitonin

Nadarajan

Toh

2021

Am J Case Rep

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“…In our previous study on this outbreak 14, we reported the detection of cosmopolitan genotype of DENV-2 (74%) and genotype I of DENV-4 (1%). In addition, we also reported the isolation of a neurotropic DENV-2 cosmopolitan genotype from the cerebrospinal fluid of encephalitis patients (20). In the present study, we described the emergence of genotype I of DENV-3 that was first seen in Sri Lanka during 2017-2018.…”

Section: Discussionsupporting

confidence: 58%

Emergence of Genotype I of Dengue Virus Serotype 3 during a Severe Dengue Epidemic in Sri Lanka in 2017

et al. 2021

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During the 2017 outbreak of severe dengue in Sri Lanka, dengue virus (DENV) serotypes 2, 3 and 4 were co-circulating. Based on our previous study on the 295 patients from the National Hospital Kandy in Sri Lanka between March 2017-January 2018, the dominant infecting serotype was DENV-2. Here, we aimed to characterize the DENV-3 strains from non-severe and severe dengue patients from our previous study population. Patients' clinical records and previous laboratory tests including dengue-specific nonstructural protein 1 antigen rapid test, IgM-capture and IgG enzymelinked immunosorbent assays, were analyzed together with the present results of real-time reverse transcription polymerase chain reaction, and next-generation sequencing of DENV-3. Based on complete genome analysis, DENV-3 isolates belonged to two different clades of genotype I and were genetically close to the strains from Indonesia, China, Singapore, Malaysia and Australia. There were sixteen amino acid changes among DENV-3 isolates, and the greater number of changes was found in nonstructural than structural proteins. The emergence of DENV-3 genotype I was noted for the first time in Sri Lanka. Continuous monitoring of this newly emerged genotype and other DENV serotypes/genotypes are needed to determine their effects on future outbreaks and to understand the molecular epidemiology of dengue.

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“…Amino acid variants were detected using Lofreq [ 25 ] and Varscan v2.4.3 [ 26 ], and the results were counter-checked with Pilon [ 27 ], V-phaser-2 [ 28 ], SNVer, and freebayes [ 29 ]. SAMtools v1.9 was then used to generate the consensus sequence [ 30 ]. Pre-processing of the data was performed using GATK v3.8.1 and Picard v2.20 [ 30 ].…”

Section: Methodsmentioning

confidence: 99%

Emergence of a Novel Dengue Virus 3 (DENV-3) Genotype-I Coincident with Increased DENV-3 Cases in Yangon, Myanmar between 2017 and 2019

Soe

Tun

Nabeshima

et al. 2021

Viruses

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Dengue fever, caused by the mosquito-borne dengue virus (DENV), has been endemic in Myanmar since 1970 and it has become a significant public health burden. It is crucial that circulating DENV strains are identified and monitored, and that their transmission efficiency and association with disease severity is understood. In this study, we analyzed DENV-1, DENV-2, DENV-3, and DENV-4 serotypes in 1235 serum samples collected in Myanmar between 2017 and 2019. Whole-genome sequencing of DENV-1–4 demonstrated that most DENV-1–4 strains had been circulating in Myanmar for several years. We also identified the emergence of DENV-3 genotype-I in 2017 samples, which persisted through 2018 and 2019. The emergence of the strain coincided with a period of increased DENV-3 cases and marked changes in the serotype dynamics. Nevertheless, we detected no significant differences between serum viral loads, disease severity, and infection status of individuals infected with different DENV serotypes during the 3-year study. Our results not only identify the spread of a new DENV-3 genotype into Yangon, Myanmar, but also support the importance of DENV evolution in changing the epidemic dynamics in endemic regions.

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Complete genome analysis and characterization of neurotropic dengue virus 2 cosmopolitan genotype isolated from the cerebrospinal fluid of encephalitis patients

Cited by 19 publications

References 47 publications

A Rare Case of Dengue Encephalitis with Raised Procalcitonin

A Rare Case of Dengue Encephalitis with Raised Procalcitonin

Emergence of Genotype I of Dengue Virus Serotype 3 during a Severe Dengue Epidemic in Sri Lanka in 2017

Emergence of a Novel Dengue Virus 3 (DENV-3) Genotype-I Coincident with Increased DENV-3 Cases in Yangon, Myanmar between 2017 and 2019

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