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

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. Author summaryChikungunya disease is a mosquito-borne viral infection which causes an acute febrile illness often associated with debilitating polyarthralgia. It is estimated that over three quarters of the world's populations live in areas at-risk of chikungunya virus transmission and to date, no efficacious medical countermeasures exist. To guide vaccine development against chikungunya, data regarding where and when outbreaks occur are needed. We conducted a systematic literature review to describe the global epidemiology of chikungunya to inform vaccine development. We used well-defined methods to search for and identify relevant research published between 1, January 1999 and 13, June 2020 in MEDLINE and other publicly available sources. We reviewed 371 references which emphasized the global expansion of chikungunya since its reemergence in 2004. Gaps in epidemiological knowledge identified included the population at risk, magnitude of outbreaks, and duration of natural immunity. This information is essential for late-stage development of chikungunya vaccines.