The global epidemiology of chikungunya from 1999 to 2020: A systematic literature review to inform the development and introduction of vaccines

Abstract

Chikungunya fever is an acute febrile illness that is often associated with severe polyarthralgia in humans. The disease is caused by chikungunya virus (CHIKV), a mosquito-borne alphavirus. Since its reemergence in 2004, the virus has spread throughout the tropical world and several subtropical areas affecting millions of people to become a global public health issue. Given the significant disease burden, there is a need for medical countermeasures and several vaccine candidates are in clinical development. To characterize the global epidemiology of chikungunya and inform vaccine development, we undertook a systematic literature review in MEDLINE and additional public domain sources published up to June 13, 2020 and assessed epidemiological trends from 1999 to 2020. Observational studies addressing CHIKV epidemiology were included and studies not reporting primary data were excluded. Only descriptive analyses were conducted. Of 3,883 relevant sources identified, 371 were eligible for inclusion. 46% of the included studies were published after 2016. Ninety-seven outbreak reports from 45 countries and 50 seroprevalence studies from 31 countries were retrieved, including from Africa, Asia, Oceania, the Americas, and Europe. Several countries reported multiple outbreaks, but these were sporadic and unpredictable. Substantial gaps in epidemiological knowledge were identified, specifically granular data on disease incidence and age-specific infection rates. The retrieved studies revealed a diversity of methodologies and study designs, reflecting a lack of standardized procedures used to characterize this disease. Nevertheless, available epidemiological data emphasized the challenges to conduct vaccine efficacy trials due to disease unpredictability. A better understanding of chikungunya disease dynamics with appropriate granularity and better insights into the duration of long-term population immunity is critical to assist in the planning and success of vaccine development efforts pre and post licensure.

Fig 1. Flow diagram of the literature search according to PRISMA.

All references identified in the online database searches were assigned a unique identification number. Following title and abstract review, duplicates were removed and articles further excluded based on the following inclusion/exclusion criteria: 1) Studies published in English, French, Spanish or Portuguese were included. 2) Studies addressing chikungunya virus infection or disease, conducted in any region, based on the general population or in any age group(s) were included. 3) Surveillance data from grey literature sources were also included. 4) Studies/reports focusing exclusively on imported cases of chikungunya, studies pertaining to diagnostic development, health economics, social sciences, case reports/series, author opinions, reviews or other studies not reporting on primary data, and non-human data were excluded.

Fig 2. Number of references per year of publication and region of study setting.

Circles are proportional to the number of studies. Circles with values lower than 10 are not labeled. Three references reported research in more than one region.