Interdependence between confirmed and discarded cases of dengue, chikungunya and Zika viruses in Brazil: A multivariate time-series analysis
Authors: Oliveira Juliane F , Rodrigues Moreno S. , Skalinski Lacita M. , Santos Aline ES , Costa Larissa C. , Cardim Luciana L. , Paixão Enny S. , da Conceição N. Costa Maria , Oliveira Wanderson K. , Barreto Maurício L. , Glória Teixeira Maria , Andrade Roberto F. S. 
Published: July 2019

The co-circulation of different arboviruses in the same time and space poses a significant threat to public health given their rapid geographic dispersion and serious health, social, and economic impact. Therefore, it is crucial to have high quality of case registration to estimate the real impact of each arboviruses in the population. In this work, a Vector Autoregressive (VAR) model was developed to investigate the interrelationships between discarded and confirmed cases of dengue, chikungunya, and Zika in Brazil. We used data from the Brazilian National Notifiable Diseases Information System (SINAN) from 2010 to 2017. There were two waves in the series of dengue notification in this period, one occurring in 2013 and the second in 2015. The series of reported cases of both Zika and chikungunya reached their peak in late 2015 and early 2016. The VAR model shows that the Zika series have a significant impact on the dengue series and vice versa, suggesting that several discarded and confirmed cases of dengue could actually have been cases of Zika. The model also suggests that the series of confirmed chikungunya cases is almost independent of the cases of dengue and Zika. In conclusion, co-circulation of arboviruses with similar symptoms could lead to misdiagnosed diseases in the surveillance system. We argue that the use of mathematical and statistical models routinely in association with traditional symptom-surveillance could help to decrease such errors and to provide early indication of possible future outbreaks. These findings address the challenges regarding notification biases and shed new light on how to handle reported cases based only in clinical-epidemiological criteria when multiples arboviruses co-circulate in the same population.

Author summary

Arthropod-borne viruses (arboviruses) transmission is a growing health problem worldwide. The real epidemiological impact of the co-circulation of different arboviruses in the same urban spaces is a recent phenomenon and there are many issues to explore. One of this issue is the misclassification due to the scarce availability of confirmatory laboratory tests. This establishes a challenge to identify, distinguish and estimate the number of infections when different arboviruses co-circulate. We propose the use of multivariate time series analysis to understand how the weekly notification of suspected cases of dengue, chikungunya and Zika, in Brazil, affected each other. Our results suggest that the series of Zika significantly impact on the series of dengue and vice versa, indicating that several discarded and confirmed cases of dengue might actually have been Zika cases. The results also suggest that the series of confirmed cases of chikungunya are almost independent of those of dengue and Zika. Our findings shed light on yet hidden aspects on the co-circulation of these three viruses based on reported cases. We believe the present work provides a new perspective on the longitudinal analysis of arboviruses transmission and call attention to the challenge in dealing with biases in the notification of multiple arboviruses that circulate in the same urban environment.