Severity of Primary and Secondary Dengue Virus 1 Infections: A Hospital-Based Study in Puerto Rico, 2012-2014

Dengue is the most common mosquito-borne viral disease in humans. Although many dengue virus (DENV) infections are asymptomatic or produce only mild illness, DENV can occasionally cause severe and fatal disease. In this study, we compared the severity of primary and secondary DENV-1 infections among patients enrolled in a prospective, hospital-based, acute febrile illnesses surveillance system in Puerto Rico (2012-2014). Serum samples collected <7 days after symptom onset were tested for DENV-serotypes by a real time-polymerase chain reaction assay. The positive samples that were collected ≤5 days after onset were then tested by a DENV IgG antibody ELISA to classify primary (IgG negative) and secondary (IgG positive) infections. Overall, 720 dengue infections (679 DENV-1, 3 DENV-2, and 38 DENV-4) were diagnosed during the study period. Of the 679 DENV-1 patients, 595 were included in the study, 445 (75%) were classified as secondary infections, and 150 (25%) as primary infections. Among these patients, 150 (25%) were classified as severe dengue. Severe dengue occurred in 28% of secondary DENV-1 infections. Severe disease was also common among primary DENV-1 infections, including 27% with plasma leakage, 15% with severe dengue, and 9% requiring admission to the intensive care unit. Even though DENV-1 has caused thousands of cases in Puerto Rico, this is the first report describing DENV-1 as the cause of severe primary infection in this country. Although secondary DENV-1 infections have an increased risk for severe disease, it is important for clinicians to be aware that any individual with dengue should be considered at risk for severe dengue.