Virus-specific differences in rates of disease during the 2010 Dengue epidemic in Puerto Rico

Abstract

Background: Dengue is a potentially fatal acute febrile illness (AFI) caused by four mosquito-transmitted dengue viruses (DENV-1-4) that are endemic in Puerto Rico. In January 2010, the number of suspected dengue cases reported to the passive dengue surveillance system exceeded the epidemic threshold and an epidemic was declared soon after.

Methodology/principal findings: To characterize the epidemic, surveillance and laboratory diagnostic data were compiled. A suspected case was a dengue-like AFI in a person reported by a health care provider with or without a specimen submitted for diagnostic testing. Laboratory-positive cases had: (i) DENV nucleic acid detected by reverse transcriptase-polymerase chain reaction (RT-PCR) in an acute serum specimen; (ii) anti-DENV IgM antibody detected by ELISA in any serum specimen; or (iii) DENV antigen or nucleic acid detected in an autopsy-tissue specimen. In 2010, a total of 26,766 suspected dengue cases (7.2 per 1,000 residents) were identified, of which 46.6% were laboratory-positive. Of 7,426 RT-PCR-positive specimens, DENV-1 (69.0%) and DENV-4 (23.6%) were detected more frequently than DENV-2 (7.3%) and DENV-3 (<0.1%). Nearly half (47.1%) of all laboratory-positive cases were adults, 49.7% had dengue with warning signs, 11.1% had severe dengue, and 40 died. Approximately 21% of cases were primary DENV infections, and 1-4 year olds were the only age group for which primary infection was more common than secondary. Individuals infected with DENV-1 were 4.2 (95% confidence interval [CI]: 1.7-9.8) and 4.0 (95% CI: 2.4-6.5) times more likely to have primary infection than those infected with DENV-2 or -4, respectively.

Conclusions/significance: This epidemic was long in duration and yielded the highest incidence of reported dengue cases and deaths since surveillance began in Puerto Rico in the late 1960's. This epidemic re-emphasizes the need for more effective primary prevention interventions to reduce the morbidity and mortality of dengue.

Figure 1. Epidemic curve of suspected dengue cases by week of illness onset, Puerto Rico, 2010.

Surveillance data from cases reported via the Passive Dengue Surveillance System, Enhanced Dengue Surveillance System, Notifiable Diseases Surveillance System, or private laboratory dengue diagnostic test results were compiled and grouped by diagnostic test result as indicated.

Figure 2. Rates of laboratory-positive cases by municipality, Puerto Rico, 2010.

Rates were calculated by dividing case numbers by municipality-specific populations and grouping by quintile of rate of all laboratory-positive cases. Rates shown are: (A) All laboratory-positive cases; or laboratory-positive cases with DENV-1 (B), DENV-2 (C), or DENV-4 (D) detected by RT-PCR.

Figure 3. Age distribution of laboratory-positive cases, Puerto Rico, 2010.

A: Age distribution and rates of laboratory-positive cases; B: Age distribution and incidence of RT-PCR-positive cases by infecting DENV-type; C: Primary and secondary DENV infections by age group from a representative sample of RT-PCR-positive cases; error bars indicate standard error of the mean; denominators by age group are 15, 21, 73, 146, 162, 115, 74, 66, 54, 61 and 31, respectively.

Figure 4. Maximum likelihood trees depicting the phylogenetic relationships of DENV-1, -2, and -4 isolated in Puerto Rico, 2010.

Each phylogeny was tested with 1,000 bootstrapping cycles. Each taxa label consists of country of origin (PR = Puerto Rico), year of virus isolation, and GenBank accession number. Viruses isolated and sequenced for this investigation are labeled with a black dot. Genotype names were based on previously published phylogenies , . All outgroups have been removed. A: Phylogenies were constructed using 29 DENV-1 E gene sequences: seven from Puerto Rico in 2010, and 22 obtained from GenBank to represent the three main genotypes: American-African, South Pacific, and Asian. B: Phylogenies were constructed using 24 DENV-2 E gene sequences: two from Puerto Rico in 2010, and 22 obtained from GenBank to represent the three main genotypes: American-Asian, Cosmopolitan, and Asian II. C: Phylogenies were constructed using 26 DENV-4 E gene sequences: four from Puerto Rico in 2010, and 22 obtained from GenBank to represent the two main genotypes: Indonesian and South East Asian.