A new analysis shows that targeting high-risk regions with the IXCHIQ vaccine could dramatically curb the global impact of chikungunya, offering hope against this rapidly spreading mosquito-borne virus.
Study: Global burden of chikungunya virus infections and the potential benefit of vaccination campaigns. Image Credit: frank60 / Shutterstock
In a recent review in the journal Nature Medicine, researchers attempted to quantify the global disease burden of chikungunya viruses (CHIKV) and identify high-risk populations, as well as evaluate the potential impacts of the first licensed anti-CHIKV vaccines. The study specifically models the potential impact of the recently licensed IXCHIQ vaccine (VLA1553, Valneva), not VIMKUNYA, which received approval from the United States Food and Drug Administration (FDA) and European Medicines Agency (EMA), respectively. Importantly, IXCHIQ was licensed based on immunological correlates of protection rather than classical phase 3 efficacy data, due to the unpredictable nature of chikungunya outbreaks. Study findings reveal that of the 180 countries analyzed, 104 experienced CHIKV transmission, corresponding to 2.8 billion exposed individuals, 35.3 million (95% CI: 20.9–56.5 million) annual CHIKV infections, and epidemic outbreaks every ~6.2 years.
Vaccination models assumed 70% vaccine efficacy, 40% infection protection, and 50% coverage (individuals ≥12 yrs). These models reveal that targeted vaccination programs could prevent 4,400 (95% CI: 3,800–4,800) infections, 0.35 (0.30–0.37) deaths, and 17 (15–19) disability-adjusted life years (DALYs) per 100,000 doses, highlighting the potential of strategic vaccination programs in significantly reducing CHIKV’s disease burden and human suffering. However, these outcomes are based on modelled scenarios and remain sensitive to key assumptions regarding vaccine characteristics, coverage, duration of protection, and speed of outbreak detection and response.
The impact of vaccination is projected to be higher in epidemic settings than in endemic settings, with a noted 83% greater effect in epidemic regions.
Endemic: CHIKV circulates persistently in the territory, with infections occurring every year. Epidemic: CHIKV circulates sporadically in the territory, with outbreaks being followed by years without detected circulation. No transmission: CHIKV does not circulate in the territory. Good evidence: Epidemiological data from disease surveillance and/or serological data and/or entomological data provide robust evidence for the given classification. Insufficient evidence: Epidemiological, serological, and entomological data do not provide robust evidence to support the given likely classification.
Background
Chikungunya is a mosquito-borne viral disease caused by the chikungunya virus (CHIKV), an RNA virus belonging to the Alphavirus genus within the family Togaviridae. Primarily transmitted by bites from infected Aedes mosquitoes (Aedes aegypti and Aedes albopictus), the disease is characterized by the sudden onset of fever, joint pain (arthralgia), and rashes, with approximately 50% of detected acute cases developing chronic joint pain that may persist for several months.
While CHIKV-associated mortality is rare (~1 death per 1,000 cases), its high (and reportedly increasing) prevalence in tropical and subtropical regions, frequent endemic transmission and sporadic epidemic episodes, and non-uniform demographic outcomes (neonates, infants, and older individuals are at significantly higher acute disease risk than healthy adults) underscores the need for global monitoring and strategic intervention deployment for optimal public health benefits.
Despite decades of research, few clinical interventions and limited epidemiological data exist for CHIKV. The former concern has been recently addressed with the licensing of the Coalition of Epidemic Preparedness Innovations (CEPI)’s novel anti-CHIKV vaccine (IXCHIQ) by both the United States (FDA) and European (EMA) public health agencies. The study mentions the approval of the VIMKUNYA vaccine, but modeling projections were conducted only for IXCHIQ.
Unfortunately, since CHIKV’s global burden remains poorly quantified, the potential public health impact of IXCHIQ and other vaccines remains unclear. Understanding the disease’s global reach is imperative before effective immunization strategies can be developed and deployed.
About the review
The present review addresses these knowledge gaps by integrating multidisciplinary data sources (seroprevalence data, surveillance systems data, and geographic mosquito distribution patterns) to estimate CHIKV’s global burden and model the potential benefits of vaccination campaigns. It aims to guide policymakers on where and when to deploy vaccines to curb the disease and disability burden.
Study data was obtained via a literature review of Google, Google Scholar, PubMed, GIDEON, WHO/PAHO, and ProMED digital scientific repositories. Studies investigating countries and territories with population sizes of 200,000 or more (n = 180) were included in subsequent analyses. Where available, age-stratified seroprevalence data (n = 49), surveillance systems data (from National Ministry of Health websites), and mosquito vector maps (Aedes aegypti and Aedes albopictus) were extracted.
Researchers used statistical models to compute: 1. Associations between mosquito vector data and CHIKV prevalence, 2. Country/territory-specific epidemic status (using the Healthcare Access and Quality [HAQ] Index), and 3. CHIKV transmission dynamics (using a custom Markov chain Monte Carlo [MCMC]-leveraging serocatalytic model). The results from these models were subsequently used to inform: 1. Epidemic CHIKV models, 2. Endemic CHIKV models, and 3. Vaccination simulations.
Vaccination simulations assumed a 70% efficacy rate, a 40% reduction in infection prevention, and a 50% population coverage rate. Outcomes were presented as ‘per 100,000 doses’, providing both burden quantification and a vaccine-impact forecast to inform public health decision-making. The authors emphasize that their projections are sensitive to assumptions regarding vaccine efficacy, protection duration, rollout logistics, and the accuracy of disease surveillance.
Study findings
Review analyses revealed that ~2.8 billion individuals across 104 countries and territories are exposed to CHIKV transmission, with 2.4% and 1.6% of them contracting the infection in endemic and epidemic regions, respectively. Additionally, epidemic outbreaks were predicted to occur every ~6.2 years, each of which resulted in 8.4% of the susceptible population being infected with CHIKV. Together, these findings predict ~35.3 million (20.9–56.5 million) global infections annually, with the majority of cases concentrated in Africa, Southeast Asia, and the Americas.
Vaccination simulations suggest that every 100,000 IXCHIQ doses administered could avert 4,400 (3,800–4,800) CHIKV infections, prevent 0.35 (0.30–0.37) deaths, and save 17 (15–19) DALYs. Vaccination projections further suggest that IXCHIQ can provide substantial protective benefits at the population level, underscoring the benefits of deploying vaccines where and when outbreaks are imminent. The impact of vaccination is projected to be greater in epidemic settings compared to endemic settings. The authors note that mixed or locally adapted immunization strategies may be required within countries.
The paper also compares chikungunya’s burden to that of dengue virus, noting that while CHIKV causes fewer symptomatic cases overall, both diseases disproportionately affect the same regions, and the patterns of endemic and epidemic transmission differ. The authors highlight that a significant proportion of CHIKV infections may be subclinical, meaning true infection numbers are likely higher than reported case data.
Vaccine safety considerations are addressed, with clinical trial data showing that severe adverse events occurred in approximately 2% of recipients and mild-to-moderate arthralgia in up to 18%, although these were not included in the DALY calculations. Ongoing and future phase 4 studies are expected to further clarify the real-world effectiveness and safety profile of these vaccines.
Together, these findings provide a quantified rationale for prioritizing high-risk regions and inform public health agencies of the ideal immunization strategies to reduce CHIKV-related morbidity and mortality worldwide.
Conclusions
This review presents the first comprehensive estimate of CHIKV’s global burden, demonstrating the potential of CEPI’s novel IXCHIQ (modeled) and VIMKUNYA (approved but not modeled) vaccines in mitigating disease outcomes, thereby preventing thousands of infections, dozens of Disability-Adjusted Life Years (DALYs), and CHIKV-associated mortality per 100,000 doses in outbreak settings. It highlights high-risk regions (countries or territories), their endemic or epidemic status, and the strategic importance of timely CHIKV vaccinations.
Overall, this review informs IXCHIQ deployment policy by utilizing evidence-based transmission and risk data, thereby optimizing vaccine use to significantly reduce disease and suffering. However, the authors caution that the modelled benefits depend on rapid outbreak detection, efficient stockpile deployment, and the ability to adapt vaccination strategies to local epidemiology and healthcare infrastructure.
Journal reference:
- Ribeiro dos Santos, G., Jawed, F., Mukandavire, C. et al. Global burden of chikungunya virus infections and the potential benefit of vaccination campaigns. Nature Medicine (2025), DOI – 10.1038/s41591-025-03703-w, https://www.nature.com/articles/s41591-025-03703-w
Article Revisions
- Jun 12 2025 - Ensured that all Latin names of biological taxa (e.g., Aedes aegypti, Alphavirus, Togaviridae) were correctly italicized per scientific writing conventions.