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Impact of dengue virus (DENV) co-infection on clinical manifestations, disease severity and laboratory parameters

Dhanoa, Amreeta, Hassan, Sharifah, Ngim, Chin Fang, Lau, Chun Fatt, Chan, Teik Seng, Adnan, Nur Amelia Azreen, Eng, Wilhelm Wei Han, Gan, Han Ming and Rajasekaram, Ganeswrie 2016, Impact of dengue virus (DENV) co-infection on clinical manifestations, disease severity and laboratory parameters, BMC infectious diseases, vol. 16, pp. 1-14, doi: 10.1186/s12879-016-1731-8.

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Title Impact of dengue virus (DENV) co-infection on clinical manifestations, disease severity and laboratory parameters
Author(s) Dhanoa, Amreeta
Hassan, Sharifah
Ngim, Chin Fang
Lau, Chun Fatt
Chan, Teik Seng
Adnan, Nur Amelia Azreen
Eng, Wilhelm Wei Han
Gan, Han Ming
Rajasekaram, Ganeswrie
Journal name BMC infectious diseases
Volume number 16
Article ID 406
Start page 1
End page 14
Total pages 14
Publisher BioMed Central
Place of publication London, Eng.
Publication date 2016-08-11
ISSN 1471-2334
Keyword(s) Clinical manifestations
Co-infection
DENV
Dengue virus
RT-PCR
Serotype
Adolescent
Adult
Aged
Child
Child, Preschool
Coinfection
Dengue
Disease Outbreaks
Female
Humans
Male
Middle Aged
Multiplex Polymerase Chain Reaction
Multivariate Analysis
Odds Ratio
Phylogeny
RNA, Viral
Retrospective Studies
Reverse Transcriptase Polymerase Chain Reaction
Serogroup
Severity of Illness Index
Viral Nonstructural Proteins
Young Adult
Summary BACKGROUND: The co-circulation of 4 DENV serotypes in geographically expanding area, has resulted in increasing occurrence of DENV co-infections. However, studies assessing the clinical impact of DENV co-infections have been scarce and have involved small number of patients. This study explores the impact of DENV co-infection on clinical manifestations and laboratory parameters.

METHODS: This retrospective study involved consecutive hospitalized patients with non-structural protein 1 (NS1) antigen positivity during an outbreak (Jan to April 2014). Multiplex RT-PCR was performed directly on NS1 positive serum samples to detect and determine the DENV serotypes. All PCR-positive serum samples were inoculated onto C6/36 cells. Multiplex PCR was repeated on the supernatant of the first blind passage of the serum-infected cells. Random samples of supernatant from the first passage of C6/36 infected cells were subjected to whole genome sequencing. Clinical and laboratory variables were compared between patients with and without DENV co-infections.

RESULTS: Of the 290 NS1 positive serum samples, 280 were PCR positive for DENV. Medical notes of 262 patients were available for analysis. All 4 DENV serotypes were identified. Of the 262 patients, forty patients (15.3 %) had DENV co-infections: DENV-1/DENV-2(85 %), DENV-1/DENV-3 (12.5 %) and DENV-2/DENV-3 (2.5 %). Another 222 patients (84.7 %) were infected with single DENV serotype (mono-infection), with DENV- 1 (76.6 %) and DENV- 2 (19.8 %) predominating. Secondary dengue infections occurred in 31.3 % patients. Whole genome sequences of random samples representing DENV-1 and DENV-2 showed heterogeneity amongst the DENVs. Multivariate analysis revealed that pleural effusion and the presence of warning signs were significantly higher in the co-infected group, both in the overall and subgroup analysis. Diarrhoea was negatively associated with co-infection. Additionally, DENV-2 co-infected patients had higher frequency of patients with severe thrombocytopenia (platelet count < 50,000/mm(3)), whereas DENV-2 mono-infections presented more commonly with myalgia. Elevated creatinine levels were more frequent amongst the co-infected patients in univariate analysis. Haemoconcentration and haemorrhagic manifestations were not higher amongst the co-infected patients. Serotypes associated with severe dengue were: DENV-1 (n = 9), DENV-2 (n = 1), DENV-3 (n = 1) in mono-infected patients and DENV-1/DENV-2 (n = 5) and DENV-1/DENV-3 (n = 1) amongst the co-infected patients.

CONCLUSION: DENV co-infections are not uncommon in a hyperendemic region and co-infected patients are skewed towards more severe clinical manifestations compared to mono-infected patients.
Language eng
DOI 10.1186/s12879-016-1731-8
Field of Research 0605 Microbiology
1103 Clinical Sciences
1108 Medical Microbiology
HERDC Research category C1.1 Refereed article in a scholarly journal
ERA Research output type C Journal article
Copyright notice ©2016, The Authors
Free to Read? Yes
Use Rights Creative Commons Attribution licence
Persistent URL http://hdl.handle.net/10536/DRO/DU:30101940

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Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.