Factors predicting the severity of dengue in patients with warning signs in Rio de Janeiro, Brazil (1986-2012).

BACKGROUND: Since 1981, >12 million cases of dengue have been reported in Brazil. Early prediction of severe dengue with no warning signs is crucial to avoid progression to severe dengue. Here we aimed to identify early markers of dengue severity and characterize dengue infection in patients in Rio de Janeiro. METHODS: We evaluated early severity markers, serotypes, infection status, number of days of illness and viral loads associated with dengue fever in patients from Rio de Janeiro, Brazil through an observational retrospective study (1986-2012). We compared dengue without warning signs and dengue with warning signs/severe dengue (DWWS/SD). Infection status was classified by enzyme-linked immunosorbent assay and viraemia was quantified by quantitative real-time reverse transcription polymerase chain reaction. RESULTS: The presence of DWWS/ SD was significantly associated with younger age; patients 13-19 y of age had a significantly greater chance of presenting warning signs. Dengue virus type 3 (DENV3) was more likely to induce DWWS/SD, which was more frequent on days 4-5 of illness. CONCLUSIONS: DENV3, 4-5 d of illness and 13-19 y of age were early biomarkers of dengue severity. To our knowledge, this was the first study to analyse the characteristics of dengue severity in the state of Rio de Janeiro over 27 y of epidemics since the introduction of DENV.

Dynamics of nonstructural glycoprotein-1 in dengue patients presenting with different clinical manifestations from 1986 to 2012 in Rio de Janeiro, Brazil.

The hyperendemicity and co-circulation of different dengue serotypes in Brazil have increased the number of severe dengue cases and the rate of hospitalization for dengue. Virological and individual factors are associated with the complexity of the disease. Antigenemia levels of nonstructural glycoprotein-1 (NS1) have been associated with severe dengue. Aiming to identify a severity marker during the acute phase (days 0 to 5 of disease), the association of NS1 antigenemia with clinical presentation, sex, age range, immune response, number of days of disease, and serotype RNA levels was evaluated in serum samples of patients from the state of Rio de Janeiro clinically classified as having dengue without warning signs (DWWS) or dengue with warning signs/severe dengue (DWWS/SD). The immune response was classified by in-house enzyme-linked immunosorbent assay, antigenemia was determined by quantification of NS1, and viremia was quantified by real-time PCR. Of the total number of patients, 36.6% (74 of 202) presented warning signs/severe dengue and 72.3% (146 of 202) were classified with primary infection. DENV-2 presented an association between clinical presentation and antigenemia (P = 0.02). DENV-3 had higher levels of NS1 (P < 0.0001). This study has shown that the infecting serotype influences circulating NS1 levels in the host, as well as NS1 antigenemia may vary as to the clinical presentation of the patient infected with DENV-2. However, the criterion used to screen patients for clinical presentation, in DWWS and DWWS/SD patients, was not a good marker for dengue severity in our study.

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

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.

Fatal case of co-infection with dengue virus and Neisseria meningitidis during a dengue epidemic in the state of Rio de Janeiro, Brazil.

INTRODUCTION: Dengue and meningococcal disease are caused by two different agents: a flavivirus and a Gram-negative bacterium, respectively. The first symptoms of both diseases can be indistinct and a rapid and accurate diagnosis is crucial, considering that both diseases are associated with high morbidity and mortality, representing a major public-health problem in Brazil. CASE PRESENTATION: We report a fatal case of co-infection of dengue virus (DENV) and Neisseria meningitidis in a 54-year-old patient. The serum tested positive for DENV NS1 antigen, and N. meningitidis serogroup C was detected by nspA-PCR. Following the initial positive result for DENV infection, rRT-PCRwas performed and DENV-4 was confirmed. CONCLUSION: Our report highlights the importance of accurate differential diagnosis during periods of high circulation of DENV, in order to provide adequate management and an improved outcome.