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Chikungunya virus (CHIKV) emerged in the Americas in late 2013 to cause substantial acute and chronic morbidity. About 1.1 million cases of chikungunya were reported within a year, including severe cases and deaths. The burden of chikungunya is unclear owing to inadequate disease surveillance and underdiagnosis. Virus evolution, globalization, and climate change may further CHIKV spread. No approved vaccine or antiviral therapeutics exist. Early detection and appropriate management could reduce the burden of severe atypical and chronic arthritic disease. Improved surveillance and risk assessment are needed to mitigate the impact of chikungunya.

In this review, we highlight biological characteristics of Aedes aegypti and Aedes albopictus, 2 invasive mosquito species and primary vectors of chikungunya virus (CHIKV), that set the tone of these species' invasiveness, vector competence, and vectorial capacity (VC). The invasiveness of both species, as well as their public health threats as vectors, is enhanced by preference for human blood. Vector competence, characterized by the efficiency of an ingested arbovirus to replicate and become infectious in the mosquito, depends largely on vector and virus genetics, and most A. aegypti and A. albopictus populations thus far tested confer vector competence for CHIKV. VC, an entomological analog of the pathogen's basic reproductive rate (R₀), is epidemiologically more important than vector competence but less frequently measured, owing to challenges in obtaining valid estimates of parameters such as vector survivorship and host feeding rates. Understanding the complexities of these factors will be pivotal in curbing CHIKV transmission.

Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that recently re-emerged in many parts of the world causing large-scale outbreaks. CHIKV infection presents as a febrile illness known as chikungunya fever (CHIKF). Infection is self-limited and characterized mainly by severe joint pain and myalgia that can last for weeks or months; however, severe disease presentation can also occur in a minor proportion of infections. Among the atypical CHIKV manifestations that have been described, severe arthralgia and neurological complications, such as encephalitis, meningitis, and Guillain–Barré Syndrome, are now reported in many outbreaks. Moreover, death cases were also reported, placing CHIKV as a relevant public health disease. Virus evolution, globalization, and climate change may have contributed to CHIKV spread. In addition to this, the lack of preventive vaccines and approved antiviral treatments is turning CHIKV into a major global health threat. In this review, we discuss the current knowledge about CHIKV pathogenesis, with a focus on atypical disease manifestations, such as persistent arthralgia and neurologic disease presentation. We also bring an up-to-date review of the current CHIKV vaccine development. Altogether, these topics highlight some of the most recent advances in our understanding of CHIKV pathogenesis and also provide important insights into the current development and clinical trials of CHIKV potential vaccine candidates.

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.

Introgression of genetic material from species of the insect bacteria Wolbachia into populations of Aedes aegypti mosquitoes has been shown in randomised and non-randomised trials to reduce the incidence of dengue; however, evidence for the real-world effectiveness of large-scale deployments of Wolbachia-infected mosquitoes for arboviral disease control in endemic settings is still scarce. A large Wolbachia (wMel strain) release programme was implemented in 2017 in Rio de Janeiro, Brazil. We aimed to assess the effect of this programme on the incidence of dengue and chikungunya in the city. 67 million wMel-infected mosquitoes were released across 28 489 locations over an area of 86·8 km2 in Rio de Janeiro between Aug 29, 2017 and Dec 27, 2019. Following releases, mosquitoes were trapped and the presence of wMel was recorded. In this spatiotemporal modelling study, we assessed the effect of the release programme on the incidence of dengue and chikungunya. We used spatiotemporally explicit mathematical models applied to geocoded dengue cases (N=283 270) from 2010 to 2019 and chikungunya cases (N=57 705) from 2016 to 2019. On average, 32% of mosquitoes collected from the release zones between 1 month and 29 months after the initial release tested positive for wMel. Reduced wMel introgression occurred in locations and seasonal periods in which cases of dengue and chikungunya were historically high, with a decrease to 25% of mosquitoes testing positive for wMel during months in which disease incidence was at its highest. Despite incomplete introgression, we found that the releases were associated with a 38% (95% CI 32–44) reduction in the incidence of dengue and a 10% (4–16) reduction in the incidence of chikungunya. Stable establishment of wMel in the geographically diverse, urban setting of Rio de Janeiro seems to be more complicated than has been observed elsewhere. However, even intermediate levels of wMel seem to reduce the incidence of disease caused by two arboviruses. These findings will help to guide future release programmes. Bill & Melinda Gates Foundation and the European Research Council.

VLA1553 is a live-attenuated vaccine candidate for active immunisation and prevention of disease caused by chikungunya virus. We report safety and immunogenicity data up to day 180 after vaccination with VLA1553. This double-blind, multicentre, randomised, phase 3 trial was done in 43 professional vaccine trial sites in the USA. Eligible participants were healthy volunteers aged 18 years and older. Patients were excluded if they had history of chikungunya virus infection or immune-mediated or chronic arthritis or arthralgia, known or suspected defect of the immune system, any inactivated vaccine received within 2 weeks before vaccination with VLA1553, or any live vaccine received within 4 weeks before vaccination with VLA1553. Participants were randomised (3:1) to receive VLA1553 or placebo. The primary endpoint was the proportion of baseline negative participants with a seroprotective chikungunya virus antibody level defined as 50% plaque reduction in a micro plaque reduction neutralisation test (μPRNT) with a μPRNT50 titre of at least 150, 28 days after vaccination. The safety analysis included all individuals who received vaccination. Immunogenicity analyses were done in a subset of participants at 12 pre-selected study sites. These participants were required to have no major protocol deviations to be included in the per-protocol population for immunogenicity analyses. This trial is registered at ClinicalTrials.gov, NCT04546724. Between Sept 17, 2020 and April 10, 2021, 6100 people were screened for eligibility. 1972 people were excluded and 4128 participants were enrolled and randomised (3093 to VLA1553 and 1035 to placebo). 358 participants in the VLA1553 group and 133 participants in the placebo group discontinued before trial end. The per-protocol population for immunogenicity analysis comprised 362 participants (266 in the VLA1553 group and 96 in the placebo group). After a single vaccination, VLA1553 induced seroprotective chikungunya virus neutralising antibody levels in 263 (98·9%) of 266 participants in the VLA1553 group (95% CI 96·7–99·8; p<0·0001) 28 days post-vaccination, independent of age. VLA1553 was generally safe with an adverse event profile similar to other licensed vaccines and equally well tolerated in younger and older adults. Serious adverse events were reported in 46 (1·5%) of 3082 participants exposed to VLA1553 and eight (0·8%) of 1033 participants in the placebo arm. Only two serious adverse events were considered related to VLA1553 treatment (one mild myalgia and one syndrome of inappropriate antidiuretic hormone secretion). Both participants recovered fully. The strong immune response and the generation of seroprotective titres in almost all vaccinated participants suggests that VLA1553 is an excellent candidate for the prevention of disease caused by chikungunya virus. Valneva, Coalition for Epidemic Preparedness Innovation, and EU Horizon 2020.

Chikungunya is an emerging arthropod-borne disease that has spread from tropical endemic areas to more temperate climates of the USA and Europe. However, no specific treatment or preventive measure is yet available. We aimed to investigate the immunogenicity and safety of a live recombinant measles-virus-based chikungunya vaccine. We did a randomised, double-blind, placebo-controlled, active-comparator, phase 1, dose-escalation study at one centre in Vienna, Austria. Healthy men and women aged 18–45 years with no comorbidities were randomly assigned, by computer-generated block randomisation (block size of 14), to receive either one of three escalating doses of the measles-virus-based candidate vaccine (low dose [1·5 × 104 median tissue culture infection doses (TCID50) per 0·05 mL], medium dose [7·5 × 104 TCID50 per 0·25 mL], or high dose [3·0 × 105 TCID50 per 1·0 mL]), or the active comparator—Priorix. Participants were additionally block-randomised to receive a booster injection on either day 28 or day 90 after the first vaccination. Participants and study investigators were masked to group allocation. The primary endpoint was the presence of neutralising anti-chikungunya antibodies on day 28, as assessed by 50% plaque reduction neutralisation test. Analysis was by intention to treat and per protocol. This trial is registered with EudraCT, number 2013-001084-23. Between Nov 22, 2013, and Feb 25, 2014, we randomly assigned 42 participants to receive the low dose (n=12), the medium dose (n=12), or the high dose (n=12) of the measles-virus-based candidate vaccine, or Priorix (n=6), of whom 36 participants (86%; n=9, n=12, n=10, n=5, respectively) were included in the per-protocol population. The candidate vaccine raised neutralising antibodies in all dose cohorts after one immunisation, with seroconversion rates of 44% (n=4) in the low-dose group, 92% (n=11) in the medium-dose group, and 90% (n=10) in the high-dose group. The immunogenicity of the candidate vaccine was not affected by pre-existing anti-measles immunity. The second vaccination resulted in a 100% seroconversion for all participants in the candidate vaccine groups. The candidate vaccine had an overall good safety profile, and the rate of adverse events increased with vaccine dose and volume. No vaccination-related serious adverse events were recorded. The live recombinant measles-virus-based chikungunya vaccine had good immunogenicity, even in the presence of anti-vector immunity, was safe, and had a generally acceptable tolerability profile. This vaccine is the first promising measles-virus-based candidate vaccine for use in human beings. Themis Bioscience GmBH.

Diseases caused by Aedes-borne viruses, such as dengue, Zika, chikungunya, and yellow fever, are emerging and reemerging globally. The causes are multifactorial and include global trade, international travel, urbanisation, water storage practices, lack of resources for intervention, and an inadequate evidence base for the public health impact of Aedes control tools. National authorities need comprehensive evidence-based guidance on how and when to implement Aedes control measures tailored to local entomological and epidemiological conditions. This review is one of a series being conducted by the Worldwide Insecticide resistance Network (WIN). It describes a framework for implementing Integrated Aedes Management (IAM) to improve control of diseases caused by Aedes-borne viruses based on available evidence. IAM consists of a portfolio of operational actions and priorities for the control of Aedes-borne viruses that are tailored to different epidemiological and entomological risk scenarios. The framework has 4 activity pillars: (i) integrated vector and disease surveillance, (ii) vector control, (iii) community mobilisation, and (iv) intra- and intersectoral collaboration as well as 4 supporting activities: (i) capacity building, (ii) research, (iii) advocacy, and (iv) policies and laws. IAM supports implementation of the World Health Organisation Global Vector Control Response (WHO GVCR) and provides a comprehensive framework for health authorities to devise and deliver sustainable, effective, integrated, community-based, locally adapted vector control strategies in order to reduce the burden of Aedes-transmitted arboviruses. The success of IAM requires strong commitment and leadership from governments to maintain proactive disease prevention programs and preparedness for rapid responses to outbreaks.

Chikungunya fever (CHIKF) is an emerging infectious disease caused by an alphavirus transmitted by Aedes spp. mosquitoes. Because mosquito control programs are not highly efficient for outbreak containment, vaccines are essential to reduce the burden of disease. Although no licensed vaccine against CHIKF is yet available, many highly promising candidates are undergoing preclinical studies, and a few of them have been tested in human trials of phase 1 or 2. Here, we review recent findings regarding the need for a CHIKF vaccine and provide an update on vaccines nearing or having entered clinical trials. We also address needs to tackle bottlenecks to vaccine development-including scientific and financial barriers-and to accelerate the development of vaccines; several actions should be taken: (i) design efficacy trials to be conducted during the course of outbreaks; (ii) evaluate the opportunity for adopting the \"animal rule\"for demonstration of efficacy for regulatory purposes; (iii) strengthen the collective commitment of nations, international organizations, potential donors and industry; (iv) stimulate public and/or private partnerships to invest in vaccine development and licensure; and (v) identify potential markets for an effective and safe CHIKF vaccine.

In July 2025, China witnessed its most significant chikungunya virus (CHIKV) outbreak since 2010. As of August 1, with over 6,000 cases reported in Foshan city, Guangdong Province. Although the clinical manifestations have been relatively mild, the rapid transmission within communities warrants our attention. In this context, we emphasize our current knowledge and the necessary actions to take. Specifically, we identify critical gaps in CHIKV control efforts and assess the effectiveness of current measures. These include vector management strategies, viral genomic surveillance, the deployment of newly approved vaccines, and the development of antiviral agents. Overall, to effectively control the epidemic of CHIKV, we require a comprehensive and multifaceted strategy for its prevention and management.