Dengue severity associated with age and a new lineage of dengue virus‐type 2 during an outbreak in Rio De Janeiro, Brazil

Abstract

Dengue virus-type 2 (DENV-2) caused three outbreaks, in the years 1990, 1998, and 2008, in Rio de Janeiro, Brazil. The 2008 outbreak was the most severe in reported cases, hospitalizations, and deaths. To investigate virological and epidemiological factors that may have contributed to the pathogenic profile of 2008 epidemic, 102 patients sera obtained during the epidemic and inter-epidemic periods of three outbreaks were analysed by qRT-PCR to estimate viremia levels and their correlation with the clinical, immunological, and demographic patient characteristics. DENV-2 isolates from the outbreaks were sequenced. Two DENV-2 lineages (I and II) of the American/Asian genotype were confirmed, each exclusive for 1990-2002 and 2007-2011, respectively. The mean viremia level in the 2008 samples was two orders of magnitude higher than that of the 1990-2002 samples. Severe dengue cases increased from 31% in 1990-2002 to 69% in 2007-2011; in patients aged ≤15 years, from 3% in 1990-2002 to 37% in 2007-2011. The DENV-2 lineage II and younger age significantly contributed to the pathogenic profile of 2008 epidemic in Rio de Janeiro.

Age‐associated differences in clinical manifestations and laboratory parameters during a dengue virus type 4 outbreak in Argentina

“…Several reports have described an association of dengue severity with age . In this study, no significant differences were found in the incidence of DWWS between age groups (26.5% for <15 years vs 39.3% for >15 years; Table ), nor was there any significant correlation between the incidence of secondary infection and age groups (50.0% for <15 years vs 46.8% for >15 years; Table ).…”

“…Several reports have described an association of dengue severity with age. 6,7 In this study, no significant differences were found in the incidence of DWWS between age groups (26.5% for <15 years vs 39.3% for >15 years; Table 2), nor was there any significant correlation between the incidence of secondary infection and age groups (50.0% for <15 years vs 46.8% for >15 years; Table 2). Univariate and multivariate analyses revealed that patients over 15 years of age had a significantly increased risk of fever, retro-orbital pain, arthalgia, diarrhea, and thrombocytopenia compared to younger patients.…”

“…Univariate and multivariate analyses revealed that patients over 15 years of age had a significantly increased risk of fever, retro-orbital pain, arthalgia, diarrhea, and thrombocytopenia compared to younger patients. Conversely, pediatric patients (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14) were two times more likely to present rash than older patients (Table 2).…”

“…The latter are grouped by the World Health Organization (WHO) into three levels of disease severity: dengue without warning signs (DWoWS), a febrile illness frequently associated with rash and joint pain; dengue with warning signs (DWWS), in which the patient may also experience hemorrhage, swelling, hepatomegaly, and/or an increase in hematocrit and thrombocytopenia; and the potentially fatal severe dengue (SD), which may include severe bleeding, shock, organ failure, and respiratory distress . Differences in clinical manifestations and severity have been associated with secondary heterologous DENV infection, patient age, and virus serotype, though the underlying mechanisms of disease enhancement are still not fully characterized.…”

Inhibition of N‐myristoyltransferase1 affects dengue virus replication

“…First, we performed in silico analysis to further test the DENV‐host interactions related to the replication cycle in dendritic cells, the primary sentinel human target cell and the primary target for DENV replication and mediated immunity (Marovich et al., ; Schmid, Diamond, & Harris, ). We included DENV Serotype 2 strain 16681 in the in silico analysis (Figure ), which showed that DENV‐2 had a high abundance of predicted N ‐myristoylation sites and that DENV‐2 strains were associated with severe dengue cases and most frequently found in worldwide epidemics (Nunes et al., ; Wei & Li, ). DENV strain 16681 was isolated from a patient with a severe case of dengue fever and has been widely used to study DENV pathogenesis (Okamoto et al., ).…”