Background: Dengue poses a significant public health challenge in Peru and other endemic countries worldwide. While severe dengue is known to be associated with secondary infection at the individual level, the factors that elevate the risk of severe dengue at the population level remain poorly understood. This study leverages over 16 years of secondary data from a Peruvian dengue surveillance system to assess which type of serotype-specific circulation is associated with an increased risk of cumulative incidence of severe dengue or dengue with warning signs (SD-DWS). Methodology: This is a retrospective analysis of secondary data using the Peruvian Ministry of Health databases of dengue cases and serotyping. A mixed negative binomial regression model for repeated measures over time was employed to estimate the association between the cumulative incidence of reported SD-DWS cases per 100,000 inhabitants and serotype-specific circulation. Crude and adjusted incidence ratios (IRR) were estimated. Principal findings:  The study analyzed data from 2007 to 2022 across 19 regions of Peru, totaling 304 region-years. Data from nearly 58,000 serotype identification reports and 57,966 cases of SD-DWS were analyzed. The regions with most cumulative incidence of SD-DWS per 100,000 inhabitants during 2007 to 2022 were Madre de Dios (3859), Loreto (1518), Ucayali (1492), Tumbes (1335), and Piura (722). The adjusted model revealed a higher risk of cumulative incidence of SD-DWS when there was specific circulation of DENV-123 (aIRR 7.57 CI 4.00 – 14.31), DENV-12 (aIRR 4.66 CI 2.57 – 8.44), DENV-23 (aIRR 3.55 CI 1.75 – 7.21), or when there was circulation of DENV-2 alone or co-circulating with other serotypes (aIRR 27.7 CI 15.46 -49.63). Conclusions: Circulation of DENV-2 was associated with higher average incidence rate ratios of SD-DWS.

The authors have declared no competing interest.

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Ethics statement Our secondary data protocol was approved by the institutional review board of the Peruvian University Cayetano Heredia (SIDISI 207993, approval record number 079-01-22). The anonymized data was obtained through the public information system of the Peruvian Ministry of Health.

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The final full dataset used in our study is available on https://doi.org/10.6084/m9.figshare.25336015.v4 (Title Serotype circulation and dengue) System https://figshare.com/

https://doi.org/10.6084/m9.figshare.25336015.v4