Reduced risk of disease during postsecondary dengue virus infections

Abstract

Background: Antibodies induced by infection with any 1 of 4 dengue virus (DENV) serotypes (DENV-1-4) may influence the clinical outcome of subsequent heterologous infections. To quantify potential cross-protective effects, we estimated disease risk as a function of DENV infection, using data from longitudinal studies performed from September 2006 through February 2011 in Iquitos, Peru, during periods of DENV-3 and DENV-4 transmission.

Methods: DENV infections before and during the study period were determined by analysis of serial serum samples with virus neutralization tests. Third and fourth infections were classified as postsecondary infections. Dengue fever cases were detected by door-to-door surveillance for acute febrile illness.

Results: Among susceptible participants, 39% (420/1077) and 53% (1595/2997) seroconverted to DENV-3 and DENV-4, respectively. Disease was detected in 7% of DENV-3 infections and 10% of DENV-4 infections. Disease during postsecondary infections was reduced by 93% for DENV-3 and 64% for DENV-4, compared with primary and secondary infections. Despite lower disease rates, postsecondary infections constituted a significant proportion of apparent infections (14% [for DENV-3 infections], 45% [for DENV-4 infections]).

Conclusions: Preexisting heterotypic antibodies markedly reduced but did not eliminate the risk of disease in this study population. These results improve understanding of how preinfection history can be associated with dengue outcomes and DENV transmission dynamics.

Keywords: antibody cross-protection; dengue; dengue fever; seroepidemiology.

Figure 1.

Monthly occurrence of diagnosed dengue fever cases in Iquitos, Peru, during 2006–2010. The period during which dengue virus serotype 3 (DENV-3) transmission was predominant is denoted by green bars, and the period during which DENV-4 transmission was predominant is denoted by purple bars. The timing of each longitudinal cohort (A and B) is shown at the top of the figure; during the DENV-4 period, they overlap. Cases were detected by active community-based surveillance for febrile illness and confirmed in the laboratory. When virus was isolated, the infecting serotype is shown; otherwise, cases positive for immunoglobulin M antibody are denoted as “DENV.”

Figure 2.

Predicted risk of disease due to infection with dengue virus serotype 4 (DENV-4), as a function of age and serostatus. Naive and monotypic exposures were combined because they were statistically indistinguishable (P > .05). Curves were estimated from the best fit model (Table 3) and plotted with standard error of the mean.