Epidemiology of dengue virus in Iquitos, Peru 1999 to 2005: interepidemic and epidemic patterns of transmission

Abstract

Background: Comprehensive, longitudinal field studies that monitor both disease and vector populations for dengue viruses are urgently needed as a pre-requisite for developing locally adaptable prevention programs or to appropriately test and license new vaccines.

Methodology and principal findings: We report the results from such a study spanning 5 years in the Amazonian city of Iquitos, Peru where DENV infection was monitored serologically among approximately 2,400 members of a neighborhood-based cohort and through school-based absenteeism surveillance for active febrile illness among a subset of this cohort. At baseline, 80% of the study population had DENV antibodies, seroprevalence increased with age, and significant geographic variation was observed, with neighborhood-specific age-adjusted rates ranging from 67.1 to 89.9%. During the first 15 months, when DENV-1 and DENV-2 were co-circulating, population-based incidence rates ranged from 2-3 infections/100 person-years (p-years). The introduction of DENV-3 during the last half of 2001 was characterized by 3 distinct periods: amplification over at least 5-6 months, replacement of previously circulating serotypes, and epidemic transmission when incidence peaked at 89 infections/100 p-years.

Conclusions/significance: Neighborhood-specific baseline seroprevalence rates were not predictive of geographic incidence patterns prior to the DENV-3 introduction, but were closely mirrored during the invasion of this serotype. Transmission varied geographically, with peak incidence occurring at different times among the 8 geographic zones in approximately 16 km(2) of the city. The lag from novel serotype introduction to epidemic transmission and knowledge of spatially explicit areas of elevated risk should be considered for more effective application of limited resources for dengue prevention.

Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Figure 1. Participant enrollment and lost to follow up (LTF) for longitudinal cohort (LC) and subset school-based febrile surveillance (FS) studies carried out between January 1999 and February 2005.

All participants enrolled in LC provided blood samples taken at ∼6-month intervals that were tested by PRNT for DENV NtAbs to identify seroconversions. Entomological surveys were carried out through August 2003. Participation in FS included the LC activities plus absence monitoring in school initiated in June 2000. After August 2003, only FS participants continued to be monitored serologically. Absence monitoring in schools continued through December 2004. Participants recruited after August 2003 provided serological samples for PRNT testing and all students finishing the study provided a final serological sample between December 2004–February 2005. Inset: The distribution of the number of blood samples taken at intervals from individual participants.

Figure 2. Number of participants enrolled in a 1999–2005 cohort by age.

The percentage of enrollees providing >1 blood sample was consistent among age groups (78–87%, P = 0.17).

Figure 3. Age-specific seroprevalence rates for participants enrolled in the longitudinal cohort between February and September 1999.

Figure 4. Seroprevalence rates for cohort participants enrolled between February and September 1999 in 8 geographic zones in Iquitos, Peru.

Figure 5. Comparison of DENV seroconversion and case incidence rates between January 1999 and February 2005.

Incidence rates are expressed as cases or seroconversions per 100 person-years at risk. Symptomatic-to-asymptomatic case ratios were calculated from incidence of active dengue cases within the School surveillance program (yellow line) compared with overall seroconversion rates within susceptible (purple line) or the entire school cohort (pink line). The ratios are shown above the curves for each time period for the susceptible (purple) and entire (pink) population. Seroconversion rates assuming infection took place at the mid-point (green) or end-point (blue) of the monitoring interval are shown for the entire longitudinal cohort calculated for both the susceptible (dark) and entire (light) populations.

Figure 6. Seroincidence rates from January 1999–February 2005 in 8 geographic zones in Iquitos, Peru.

Rates are expressed in 100 person-years at risk with the overall rate for the entire study period shown in the upper left portion of each figure and the zones in the upper right. Rates were calculated for same time periods shown in Table 7.