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.

An evaluation of global Chikungunya clinical management guidelines – a systematic review

“…Although 96% (27/28) of CMGs 9, 29, 30, 32, 34–51, 53–56 included advice for older adults (CMGs generally defined as those aged over 60 or 65 years) and those with comorbidities, this advice was limited in scope. Two (22%, 2/9) stated that people over 60 years old had a 50-times higher mortality risk compared to younger adults.…”

“…9,52,53 One CMG (4%) advised against use of dipyrone in infants younger than three months or weighing less than 5kg. 54 Older adults and those with comorbidities Although 96% (27/28) of CMGs 9,29,30,32,[34][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50][51][53][54][55][56] included advice for older adults (CMGs generally defined as those aged over 60 or 65 years) and those with comorbidities, this advice was limited in scope. Two (22%, 2/9) stated that people over 60 years old had a 50-times higher mortality risk compared to younger adults.…”

Household clustering supports a novel chemoprophylaxis trial design for a mosquito-borne viral disease

“…The spread of Aedes albopictus to more temperate regions of the world may bring these diseases to increased numbers of countries in the future ( Tjaden et al, 2021 ). Chikungunya virus (CHIKV) infections typically occur in outbreaks of limited duration, although a seasonal pattern of repeated small outbreaks against a background of low-level endemicity may occur in some countries ( Bettis et al, 2022 ). Acute CHIKV infection is manifested by common symptoms of viral infections, such as a high fever of sudden onset with myalgia and headache, and is typically accompanied by severe arthralgia.…”

“…The start and location of an outbreak cannot be reliably predicted, and its duration may be limited to a number of months. The interval between outbreaks in the same location may be very long (10-20 years), or an outbreak may recur the following year if influenced by seasonal factors and if the necessary degree of local population immunity has not been achieved ( Bettis et al, 2022 ;Ribeiro et al, 2020 ). These uncertainties pose immense problems in setting up clinical trials.…”

Expected endpoints from future chikungunya vaccine trial sites informed by serological data and modeling

“…The considerable logistical difficulties associated with conducting a trial during an outbreak place even more importance on being prepared to carry out trials in locations where outbreaks may be likely. Continuing outbreaks of chikungunya globally [21] offer encouragement about the prospect of efficacy trials being possible, although current vaccine candidates have so far not been able to leverage these outbreaks as opportunities for phase-III efficacy trials required for licensure. Completion of a phase-III vaccine efficacy trial depends not just on a chikungunya outbreak occurring somewhere, but in a particular population that can be enrolled and followed during a trial.…”