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

• Published in: BMC infectious diseases Vol. 16; no. 1; p. 406
• Main Authors: Dhanoa, Amreeta, Hassan, Sharifah Syed, Ngim, Chin Fang, Lau, Chun Fatt, Chan, Teik Seng, Adnan, Nur Amelia Azreen, Eng, Wilhelm Wei Han, Gan, Han Ming, Rajasekaram, Ganeswrie
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 11.08.2016; BioMed Central
• Subjects: Adolescent; Adult; Aged; Analysis; Child; Child, Preschool; Coinfection - epidemiology; Coinfection - pathology; Coinfection - virology; Demographic aspects; Dengue - diagnosis; Dengue - epidemiology; Dengue - pathology; Dengue - virology; Dengue hemorrhagic fever; Dengue Virus - classification; Dengue Virus - genetics; Dengue Virus - isolation & purification; Dengue viruses; Disease Outbreaks; Disease transmission; Female; Genomics; Humans; Infectious diseases; Influence; Male; Middle Aged; Multiplex Polymerase Chain Reaction; Multivariate Analysis; Odds Ratio; Phylogeny; Polymerase chain reaction; Retrospective Studies; Reverse Transcriptase Polymerase Chain Reaction; RNA, Viral - isolation & purification; RNA, Viral - metabolism; Serogroup; Severity of Illness Index; Viral Nonstructural Proteins - genetics; Young Adult; Malaysia; Clinical manifestations; Co-infection; Serotype; Dengue virus; DENV; RT-PCR
• ISSN: 1471-2334; 1471-2334
• DOI: 10.1186/s12879-016-1731-8

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. 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. 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. 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.