Predicting factors of severe dengue infection: Clinical and virological features in hospitalized patients in French Guiana from 2008 to 2013.
Résumé
Dengue infections have become one of the most important worldwide mosquito-borne diseases affecting humans especially in tropical and subtropical regions. Its clinical spectrum ranges from asymptomatic or a mild febrile illness to severe and fatal disease. Even though several vaccines are being developed, no vaccine or curative treatment is currently available and treatment strategies are limited to supportive care to avoid shock syndrome. Understanding the risk factors for progression to severe dengue and death is then essential in determining triage and care management procedures. French Guiana is significantly affected with DENV infection and no study identifying risk factors associated with development of severe complications has been yet done in this territory. A prospective cohort study was conducted including all hospitalized patients in the three public hospitals of French Guiana from December 2008 to December 2013. Detailed clinical features such as the presence of warning signs, blood pressure, pulse rate, bleeding manifestations or any possible fluid accumulation in the pleural or abdomen were monitored on a daily basis, as well as biological parameters. World Health Organization 2009 criteria were applied to define classical dengue fever (A), with warning signs (B) and severe dengue (C). During the study period, 1325 patients were enrolled in the 3 hospitals. Among them, 15% patients had dengue fever without warning signs(A), 69% had dengue with warning signs (B) and 16% presented severe dengue (C). Severe infection was significantly more common in adults (> 15 years) than in children: 69.52% vs. 30.48% (p<0.0001). There were no significant differences in the duration of fever between adults and children or between the disease classifications. It was found that nausea, petechiae, epistaxis, abdominal pain and fluid accumulation were statistically more common in severe dengue cases. It was also revealed that a higher proportion of severe dengue had prolonged (2 or more days), episataxis, neurological disorders, fluid accumulation, purpura and hepatomegaly. Also lymphopenia was significantly higher in severe dengue. Regarding biological parameters at five days of illness, we found that neutrophil count and AST and ALT levels were significantly higher in severe dengue. Whereas lymphocyte counts and platelet counts at admission was significantly lower in patients with severe dengue. This first analysis helped in identifying predictors of severe dengue but next steps will allow the investigation of well-documented sera samples to study classical virological, biological and immunological parameters, and a novel virological high throughput sequencing approach to examine the viral genetic diversity associated to differential outcomes. This integrated approach could lead to the identification of new markers of disease severity and potential new targets for innovative treatments.