Clinical manifestations of dengue in relation to dengue serotype and genotype in Malaysia: A retrospective observational study

Abstract

BackgroundMalaysia experienced an unprecedented dengue outbreak from the year 2014 to 2016 that resulted in an enormous increase in the number of cases and mortality as compared to previous years. The causes that attribute to a dengue outbreak can be multifactorial. Viral factors, such as dengue serotype and genotype, are the components of interest in this study. Although only a small number of studies investigated the association between the serotype of dengue virus and clinical manifestations, none of these studies included analyses on dengue genotypes. The present study aims to investigate dengue serotype and genotype-specific clinical characteristics among dengue fever and severe dengue cases from two Malaysian tertiary hospitals between 2014 and mid-2017.Methodology and principal findingsA total of 120 retrospective dengue serum specimens were subjected to serotyping and genotyping by Taqman Real-Time RT-PCR, sequencing and phylogenetic analysis. Subsequently, the dengue serotype and genotype data were statistically analyzed for 101 of 120 corresponding patients’ clinical manifestations to generate a descriptive relation between the genetic components and clinical outcomes of dengue infected patients. During the study period, predominant dengue serotype and genotype were found to be DENV 1 genotype I. Additionally, non-severe clinical manifestations were commonly observed in patients infected with DENV 1 and DENV 3. Meanwhile, patients with DENV 2 infection showed significant warning signs and developed severe dengue (p = 0.007). Cases infected with DENV 2 were also commonly presented with persistent vomiting (p = 0.010), epigastric pain (p = 0.018), plasma leakage (p = 0.004) and shock (p = 0.038). Moreover, myalgia and arthralgia were highly prevalent among DENV 3 infection (p = 0.015; p = 0.014). The comparison of genotype-specific clinical manifestations showed that DENV 2 Cosmopolitan was significantly common among severe dengue patients. An association was also found between genotype I of DENV 3 and myalgia. In a similar vein, genotype III of DENV 3 was significantly common among patients with arthralgia.ConclusionThe current data contended that different dengue serotype and genotype had caused distinct clinical characteristics in infected patients.

Peer Review #2 of "Characterization of dengue cases among patients with an acute illness, Central Department, Paraguay (v0.1)"

“…Clinical findings in our patients appear more consistent with dengue in adults rather than dengue caused specifically by DENV-1, which is often associated with lower rates of arthralgia and myalgia (Burattini et al 2016;Martins Vdo et al 2014;Suppiah et al 2018;Yung et al 2015).…”

Leptospira interrogans and Leptospira kirschneri are the dominant Leptospira species causing human leptospirosis in Central Malaysia

“…Leptospirosis co-infection with dengue or scrub typhus is commonly seen in neighbouring countries such as Thailand and India [36][37][38][39][40][41][42][43]. Dengue is highly endemic in Malaysia with a minimum of 100,000 cases and more than 200 mortalities every year [44]. A recent study by Suppiah et al (2017) reported 11/268 (4.1%) dengue cases to be co-infected with leptospirosis [45].…”

The plausible mechanisms of action of Carica papaya on Dengue infection: A comprehensive review

“…Studies have been done to figure out the relationship between the dengue serotypes and their respective clinical manifestations. Infection with DEN-1 and DEN-3 has mild clinical manifestations, whereas infection cases with DENV-2 showed severe manifestations amongst all [5] . The infection varies from asymptomatic illness to severe ones such as haemorrhagic fever and dengue shock syndrome.…”

“…Meanwhile DENV-2 was first reported in Indonesia and Papua New Guinea and spread thru Asian regions such as Malaysia, Thailand, the Philippines and Singapore since then. Both DENV-3 and DENV-4 were reported much later in 1953 in the Philippines and Thailand [5] .…”