Meningitis Associated with Simultaneous Infection by Multiple Dengue Virus Serotypes in Children, Brazil

Marinho, Paula Eillanny Silva; Oliveira, Danilo Bretas de; Candiani, Talitah Michel Sanchez; Crispim, Ana Paula Correia; Alvarenga, Pedro Paulo Martins; Castro, Fabrizia Cristina Dos Santos; Abrahão, Jônatas Santos; Rios, María; Coimbra, Roney Santos; Kroon, Erna Geessien

doi:10.3201/eid2301.160817

Cited by 18 publications

(24 citation statements)

References 12 publications

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“…Araujo et al 24 found that 3.8% (8/209) of CSF tested positive for dengue in a study of 183 patients with suspected viral meningitis/meningoencephalitis and 26 deceased patients with suspected meningitis 24 . Marinho et al 25 detected DENV-1, -2, and -3 co-infections in 31.8% (7/22) of CSF of paediatric patients having viral meningitis 24 25 .…”

Section: Discussionmentioning

confidence: 99%

Importance of cerebrospinal fluid investigation during dengue infection in Brazilian Amazonia Region

Bastos

Martins

Silva

et al. 2019

Mem. Inst. Oswaldo Cruz

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BACKGROUND Amazon, the largest tropical forest of the world, has suffered from dengue outbreaks since 1998. Cerebrospinal fluid (CSF) of patients, from Amazonas state, suspected of central nervous system (CNS) viral infection was studied using molecular and immunological methods. OBJECTIVE To evaluate the importance of CSF investigation in patients with acute dengue virus (DENV) infection of CNS. METHODS CSF samples of 700 patients were analysed by reverse transcription polymerase chain reaction (RT-PCR) to detect the presence of dengue virus (DENV) RNA and by enzyme-linked immunosorbent assay (ELISA) to detect presence of DENV specific IgM. FINDINGS DENV infection was detected in 4.3% of the CSF samples; 85.7% (24/28) by DENV IgM and 14.3% (4/28) by viral RNA. DENV detected by viral RNA were to be found serotypes DENV-2 (three patients) and DENV-1 (one patient). The neurological diagnosis in patients CNS infection of DENV included encephalitis (10), meningoencephalitis (10), meningitis (6), acute myelitis (1), and encephalomyelitis (1). The majority (89.3%) had intrathecal inflammation: pleocytosis, hyperproteinorrachia and DENV IgM antibodies. Hypoglycorrhachia and/or high levels of lactate in CSF were found in 36% of the patients. Co-infection (CMV, HIV, EBV, and/or Mycobacterium tuberculosis) was observed in eight (28.6%) cases. CONCLUSIONS We found intense inflammatory CSF that is unusual in CNS disorders caused by dengue infection. It may be due co-infections or the immunogenetic background of the local Amerindian Brazilian population. CSF examination is an important diagnostic support tool for neurological dengue diagnosis.

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Section: Discussionmentioning

confidence: 99%

Importance of cerebrospinal fluid investigation during dengue infection in Brazilian Amazonia Region

Bastos

Martins

Silva

et al. 2019

Mem. Inst. Oswaldo Cruz

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“…An NGC-like strain detected in Jamaica in 2007, causing mild dengue disease, was also grouped within the Asian II genotype 8 . Interestingly, the Asian II genotype caused meningitis in patients from Minas Gerais, in the southeast region of Brazil 9 , within the same timeframe as our sample collection. Our results confirmed Asian II genotype of DENV-2 circulation in Brazil, in addition to the prevalent Asian/American genotype.…”

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confidence: 65%

Detection of the Asian II genotype of dengue virus serotype 2 in humans and mosquitoes in Brazil

Kubiszeski

Vieira

Thies

et al. 2020

Rev. Soc. Bras. Med. Trop.

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Introduction: DENV-2 is the cause of most dengue epidemics worldwide and is associated with severe cases. Methods: We investigated arboviruses in 164 serum samples collected from patients presenting with clinical symptoms of dengue fever and 152 mosquito pools. Results: We detected the Asian II genotype of DENV-2 in humans and mosquitoes. Our results confirmed the circulation of the Asian II genotype in Brazil, in addition to the prevalent Asian/American genotype. Conclusions: The detection of Asian II genotype of DENV-2 in mosquito pools collected in a forest park may be related to a spillback event of human dengue virus.

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“…It highlights the potential of the DEN-IM workflow to accurately detect and recover multiple DENV genomes from samples with DENV co-infection, even if the serotypes are present in low abundance. Indeed, recent studies from areas of high endemicity suggest that co-infection with multiple DENV serotypes may frequently occur [26] [27] and the co-circulation of different DENV strains of the same serotype, but distinct genotypes, in these areas [26] raises the possibility of simultaneous infection with more than one genotype.…”

Section: Discussionmentioning

confidence: 99%

DEN-IM: Dengue Virus identification from shotgun and targeted metagenomics

Mendes

Lizarazo

Machado

et al. 2019

Preprint

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Dengue virus (DENV) represents a public health and economic burden in affected countries. The availability of genomic data is key to understand viral evolution and dynamics, supporting improved control strategies. Currently, the use of High Throughput Sequencing (HTS) technologies, which can be applied both directly to patient samples (shotgun metagenomics) and to PCR amplified viral sequences (targeted metagenomics), is the most informative approach to monitor the viral dissemination and genetic diversity.Despite many advantages, these technologies require bioinformatics expertise and appropriate infrastructure for the analysis and interpretation of the resulting data. In addition, the many software solutions available can hamper reproducibility and comparison of results.Here we present DEN-IM, a one-stop, user-friendly, containerised and reproducible workflow for the analysis of DENV sequencing data, both from shotgun and targeted metagenomics approaches. It is able to infer DENV coding sequence (CDS), identify serotype and genotype, and generate a phylogenetic tree. It can easily be run on any UNIX-like system, from local machines to high-performance computing clusters, performing a comprehensive analysis without the requirement of extensive bioinformatics expertise.Using DEN-IM, we successfully analysed two DENV datasets. The first comprised 25 shotgun metagenomic sequencing samples of varying serotype and genotype, including a spiked sample containing the existing four serotypes. The second dataset consisted of 106 targeted metagenomics samples of DENV 3 genotype III where DEN-IM allowed detection of the intra-genotype diversity.The DEN-IM workflow, parameters and execution configuration files, and documentation are freely available at https://github.com/B-UMMI/DEN-IM. The Dengue virus (DENV), a single-stranded positive-sense RNA virus belonging to the Flavivirus 2 genus, is one of the most prevalent arboviruses and is mainly concentrated in tropical and subtropical 3 regions. Infection with DENV results in symptoms ranging from mild fever to haemorrhagic fever and 4 shock syndrome [1]. Transmission to humans occurs through the bite of Aedes mosquitoes namely 5 Aedes aegypti and Aedes albopictus [2] In 2010, it was predicted that the burden of dengue disease 6 reached 390 million cases per year worldwide [3]. The high morbidity and mortality of dengue makes 7 it the arbovirus with the highest clinical significance [4]. 8 The viral genome of ∼11,000 nucleotides, consists of a Coding Sequence (CDS) of approximately 910.2 Kb that is translated into a single polyprotein encoding three structural proteins (capsid -C, 10 premembrane -prM, envelope -E) and seven non-structural proteins (NS1, NS2A, NS2B, NS3, NS4A, 11 NS4B and NS5. Additionally, the genome contains two Non-Coding Regions (NCRs) at their 5' and 12 3' ends [5]. 13DENV can be classified into four serotypes (1, 2, 3 and 4), differing from each other by 25% to 14 40% at the amino acid level. They are further classified into genotypes that vary by up to ∼...

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Meningitis Associated with Simultaneous Infection by Multiple Dengue Virus Serotypes in Children, Brazil

Cited by 18 publications

References 12 publications

Importance of cerebrospinal fluid investigation during dengue infection in Brazilian Amazonia Region

Importance of cerebrospinal fluid investigation during dengue infection in Brazilian Amazonia Region

Detection of the Asian II genotype of dengue virus serotype 2 in humans and mosquitoes in Brazil

DEN-IM: Dengue Virus identification from shotgun and targeted metagenomics

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