Epidemiology and genetic diversity of circulating dengue viruses in Medellin, Colombia: a fever surveillance study

Abstract

Background: Dengue fever is a major public health problem in Colombia. A fever surveillance study was conducted for evaluation of the clinical, epidemiological, and molecular patterns of dengue, prior to Chikungunya and Zika epidemics.

Methods: In November 2011-February 2014, a passive facility-based surveillance was implemented in Santa Cruz Hospital, Medellin, and enrolled eligible febrile patients between 1 and 65 years-of-age. Acute and convalescent blood samples were collected 10-21 days apart and tested for dengue using IgM/IgG ELISA. RNA was extracted for serotyping using RT-PCR on acute samples and genotyping was performed by sequencing.

Results: Among 537 febrile patients enrolled during the study period, 29% (n = 155) were identified to be dengue-positive. Only 7% of dengue cases were hospitalized, but dengue-positive patients were 2.6 times more likely to be hospitalized, compared to non-dengue cases, based on a logistic regression. From those tested with RT-PCR (n = 173), 17 were dengue-confirmed based on PCR and/or virus isolation showing mostly DENV-3 (n = 9) and DENV-4 (n = 7) with 1 DENV-1. Genotyping results showed that: DENV-1 isolate belongs to the genotype V or American/African genotype; DENV-3 isolates belong to genotype III; and DENV-4 isolates belong to the II genotype and specifically to the IIb sub-genotype or linage.

Conclusions: Our surveillance documented considerable dengue burden in Santa Cruz comuna during non-epidemic years, and genetic diversity of circulating DENV isolates, captured prior to Chikungunya epidemic in 2014 and Zika epidemic in 2015. Our study findings underscore the need for continued surveillance and monitoring of dengue and other arboviruses and serve as epidemiological and molecular evidence base for future studies to assess changes in DENV transmission in Medellin, given emerging and re-emerging arboviral diseases in the region.

Keywords: Colombia; Dengue; Genotyping; Surveillance.

Fig. 1

A map of the study area in Santa Cruz, Medellin, Colombia. The map shows the study area in Santa Cruz, Medellin, Colombia.

Fig. 2

Patient flow for the passive fever surveillance at Santa Cruz Hospital. The chart shows the study flow when a febrile patient presents at Santa Cruz Hospital from screening and enrollment to lab testing

Fig. 3

Flow chart describing the ascertainment of the febrile patients during the study period of November 2011–February 2014. The diagram shows how we reached the study population and the test results from collected samples, within the surveillance.

Fig. 4

Monthly distribution of the enrolled febrile patients (n = 537) and dengue-positive patients (n = 155) with the serotype distribution in PCR-positive cases. The figure has two parts: the upper part shows monthly distribution of dengue-positive and non-dengue cases among the enrolled patients; and the lower part shows distribution of serotypes

Fig. 5

Maximum clade credibility tree of DENV-1 – genotype V

Fig. 6

Maximum clade credibility tree of DENV-3 – genotype III

Fig. 7

Maximum clade credibility tree of DENV-4 – genotype IIb