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Advancing Chikungunya Prevention and Vaccination in Mexico: A Position Paper from the Immunization Committee of the Mexican Association of Pediatric Infectious Diseases

Submitted:

08 July 2026

Posted:

10 July 2026

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Abstract
Background: Chikungunya virus (CHIKV) is a mosquito-borne alphavirus transmitted predominantly by Aedes aegypti and Aedes albopictus. Infection is characterized by an acute febrile illness accompanied by debilitating polyarthralgia, myalgia, and cutaneous manifestations. Although the acute syndrome is usually self-limited, a substantial proportion of patients experience persistent musculoskeletal symptoms that may progress to chronic inflammatory arthritis, resulting in prolonged disability and impaired quality of life.Objective: To summarize current evidence on the epidemiology, virology, immunopathogenesis, clinical manifestations, laboratory diagnosis, prevention, and vaccine development of CHIKV, with particular emphasis on its implications for public health policy and immunization strategies in Mexico.Methods: This position paper was developed through a structured narrative review of the scientific literature. Publications indexed in PubMed, Scopus, and Embase, together with documents issued by the World Health Organization (WHO), Pan American Health Organization (PAHO), Centers for Disease Control and Prevention (CDC), U.S. Food and Drug Administration (FDA), and European Medicines Agency (EMA), were critically reviewed. Evidence was selected according to its scientific quality and relevance to Mexico and Latin America. Because this work represents an expert consensus rather than a systematic review, formal risk-of-bias assessment was not performed.Results: CHIKV circulates through both urban and sylvatic transmission cycles and continues to expand into regions where competent mosquito vectors are established. Disease progression is driven by complex innate and adaptive immune responses, with exaggerated inflammatory activation contributing to chronic rheumatologic sequelae. Laboratory confirmation relies primarily on molecular assays during the viremic phase and serological testing thereafter. Recent advances in vaccine development—including live-attenuated and virus-like particle (VLP) platforms—have demonstrated favorable immunogenicity and acceptable safety profiles. However, vaccination should be considered as one component of an integrated prevention strategy that also includes vector surveillance, environmental control, and rapid outbreak detection.Conclusions: Chikungunya remains an emerging global public health challenge because of its expanding geographic distribution, epidemic potential, and long-term clinical consequences. Incorporating vaccination into comprehensive arboviral control programs, together with strengthened surveillance and integrated vector management, may substantially reduce disease burden. This position paper provides evidence-based recommendations to support future chikungunya prevention and vaccination policies in Mexico.
Keywords: 
chikungunya
;  
chikungunya vaccines
;  
arboviruses
;  
Mexico
;  
public health
;  
immunization policy
Subject: 
Public Health and Healthcare  -   Public Health and Health Services

1. Introduction.

Chikungunya virus (CHIKV) is a positive-sense RNA arbovirus belonging to the genus Alphavirus within the family Togaviridae. Human infection is primarily acquired through the bites of infected Aedes aegypti and Aedes albopictusmosquitoes, two highly efficient vectors that have facilitated the worldwide expansion of the disease. Clinically, chikungunya is characterized by the abrupt onset of fever accompanied by severe polyarthralgia, myalgia, and maculopapular rash. While the acute illness generally resolves within one to two weeks, complete clinical recovery is not universal. A considerable proportion of patients develop persistent inflammatory musculoskeletal manifestations that may last for months or even years, leading to chronic pain, functional impairment, and reduced health-related quality of life [1].
Since its first description in Tanzania in the early 1950s, CHIKV has evolved from a geographically restricted pathogen into a globally important arbovirus. Recurrent epidemics have affected more than one hundred countries across Africa, Asia, Europe, and the Americas, reflecting the progressive expansion of competent mosquito vectors, increasing international travel, rapid urbanization, and environmental changes associated with climate variability. These factors have facilitated viral introduction into previously unaffected regions and increased the frequency and magnitude of outbreaks [2].
Although the case-fatality rate of chikungunya remains relatively low, its public health impact is substantial because of the high proportion of symptomatic infections and the persistence of chronic rheumatologic complications. Approximately three-quarters of infected individuals develop symptomatic disease, and prolonged arthralgia or inflammatory arthritis affects a significant percentage of patients, generating long-term disability, increased healthcare utilization, and considerable socioeconomic costs [2].
For many years, prevention strategies relied almost exclusively on vector control measures and personal protection against mosquito bites. Despite these efforts, sustained transmission and recurrent epidemics continue to occur in endemic regions, highlighting the limitations of existing preventive approaches. The recent development and regulatory approval of chikungunya vaccines therefore represent a major advance and offer new opportunities to complement traditional vector-control programs and reduce the overall burden of disease [3].
Given the increasing epidemiological relevance of CHIKV and the emergence of licensed vaccines, a comprehensive evaluation of current evidence is timely. This position paper reviews the virology, epidemiology, immunopathogenesis, clinical manifestations, diagnosis, treatment, prevention, and vaccination of chikungunya, while discussing their implications for immunization policies and future prevention strategies in Mexico.

1. Methods

This position paper was informed by a structured narrative review of the available scientific literature. Relevant evidence was retrieved from PubMed, Scopus, and authoritative publications issued by international organizations, including the World Health Organization (WHO), the Pan American Health Organization (PAHO), the Centers for Disease Control and Prevention (CDC), and major regulatory authorities. Particular emphasis was placed on studies addressing the epidemiology, virology, immunopathogenesis, clinical manifestations, laboratory diagnosis, prevention, and vaccine development of chikungunya virus infection.
The literature was critically evaluated according to its scientific relevance and its applicability to public health priorities, immunization strategies, and disease prevention in Mexico and Latin America. Priority was given to recent systematic reviews, clinical trials, epidemiological studies, and evidence supporting currently licensed vaccines.
Because the objective of this manuscript was to provide an expert consensus and evidence-based recommendations rather than to conduct a systematic review, no predefined protocol, quantitative data synthesis, or formal assessment of methodological quality or risk of bias was undertaken.hisvailable scientific literature. Relevant evidence was retrieved from PubMed, Scopus, and authoritative publications issued by international organizations, including the World Health Organization (WHO), the Pan American Health Organization (PAHO), the Centers for Disease Control and Prevention (CDC), and major regulatory authorities. Particular emphasis was placed on studies addressing the epidemiology, virology, immunopathogenesis, clinical manifestations, laboratory diagnosis, prevention, and vaccine development of chikungunya virus infection.
The literature was critically evaluated according to its scientific relevance and its applicability to public health priorities, immunization strategies, and disease prevention in Mexico and Latin America. Priority was given to recent systematic reviews, clinical trials, epidemiological studies, and evidence supporting currently licensed vaccines.
Because the objective of this manuscript was to provide an expert consensus and evidence-based recommendations rather than to conduct a systematic review, no predefined protocol, quantitative data synthesis, or formal assessment of methodological quality or risk of bias was undertaken.

Rationale

The global resurgence of chikungunya virus (CHIKV) infection and its progressive geographic expansion have reinforced the need for preventive strategies that extend beyond conventional vector-control measures. Since the introduction of CHIKV into the Americas in 2013, successive outbreaks have affected millions of individuals, imposing a considerable clinical, economic, and public health burden across tropical and subtropical regions. The widespread distribution of Aedesmosquitoes, together with increasing human mobility, urbanization, and the persistence of immunologically susceptible populations, indicates that the risk of future epidemics will likely remain substantial [3].
The recent availability of licensed chikungunya vaccines represents a major advance in the prevention of this emerging arboviral disease. Multiple vaccine technologies—including live-attenuated, inactivated, and virus-like particle (VLP)-based platforms—have been investigated, with several candidates demonstrating favorable immunogenicity and acceptable safety profiles during clinical development. In particular, phase 3 studies of live-attenuated vaccines have shown high seroconversion rates and durable neutralizing antibody responses following a single dose, leading to the first regulatory approvals for the prevention of chikungunya in selected populations [4].
Despite these advances, several challenges remain before widespread implementation can be considered. Critical issues include identifying the populations most likely to benefit from vaccination, defining risk-based vaccination strategies, evaluating long-term effectiveness and safety, and determining how these vaccines should be incorporated into existing public health programs. Consequently, organizations such as the World Health Organization (WHO), the Centers for Disease Control and Prevention (CDC), and national and international immunization advisory groups have undertaken comprehensive evaluations of the available evidence to support evidence-based vaccination recommendations [5,6,7].
Given the rapidly evolving landscape of chikungunya prevention, a comprehensive appraisal of current scientific evidence is warranted. This position paper critically reviews the available data on vaccine platforms, immunogenicity, efficacy, safety, and implementation strategies while discussing their potential implications for vaccination policies and public health decision-making in Mexico.

Virus Characteristics

Chikungunya virus (CHIKV) is an enveloped, positive-sense single-stranded RNA virus belonging to the genus Alphavirus within the family Togaviridae. Mature viral particles measure approximately 60–70 nm in diameter and display an icosahedral nucleocapsid enclosed by a host-derived lipid bilayer. Embedded within this envelope are approximately 80 trimeric glycoprotein spikes that project from the virion surface and play essential roles in host-cell recognition and viral entry. The viral genome is approximately 11.8 kb in length and contains both a 5′ methylated cap and a 3′ polyadenylated tail, structural features required for efficient translation and replication within infected cells [8,9].
The CHIKV genome is organized into two major open reading frames (ORFs), each fulfilling distinct biological functions. The 5′ ORF encodes four non-structural proteins (nsP1–nsP4), which assemble into the viral replication complex responsible for RNA replication and transcription. In contrast, the 3′ ORF encodes a structural polyprotein that undergoes proteolytic processing to generate the capsid protein and the envelope-associated proteins E3, E2, 6K/transframe (TF), and E1. These structural components coordinate viral assembly, encapsidation of the genomic RNA, and formation of mature infectious virions [10].
Among the viral structural proteins, the envelope glycoproteins E1 and E2 are of particular biological and immunological importance because they constitute the principal targets of neutralizing antibodies induced by natural infection and vaccination. These glycoproteins assemble as E1–E2 heterodimers that subsequently organize into trimeric spikes covering the viral surface. Functionally, E2 mediates host-cell receptor recognition and virus attachment, whereas E1 contains the fusion peptide that promotes membrane fusion following endosomal acidification, thereby allowing release of the nucleocapsid into the cytoplasm and initiation of viral replication [8,11].
Substantial advances in structural virology have identified matrix-remodeling associated protein 8 (MXRA8) as the major cellular receptor facilitating CHIKV entry into susceptible cells. High-resolution structural studies have demonstrated that each trimeric E1–E2 spike simultaneously interacts with three MXRA8 molecules through specific contacts involving the D1 and D2 receptor domains. This multivalent interaction stabilizes viral attachment, promotes internalization, and contributes to the characteristic tissue tropism observed during CHIKV infection, particularly within musculoskeletal tissues [12,13,14].

Pathophysiology

Following inoculation by an infected Aedes mosquito, chikungunya virus (CHIKV) establishes infection through rapid replication at the site of the mosquito bite, resulting in high-level viremia and activation of both innate and adaptive immune responses. Viral entry is mediated by interactions between the E2 envelope glycoprotein and host-cell glycosaminoglycans, together with binding to matrix-remodeling associated protein 8 (MXRA8), the principal cellular receptor identified for CHIKV. This receptor-mediated process facilitates viral internalization and initiates infection after an incubation period that typically ranges from 2 to 12 days [13,14,15].
The earliest cellular targets include dermal fibroblasts, keratinocytes, endothelial cells, and resident macrophages within the skin. Once internalized, the viral positive-sense RNA genome is translated to generate the non-structural proteins required for viral replication, while a subgenomic RNA directs the synthesis of structural proteins necessary for assembly and release of new virions. High expression of MXRA8 in synovial fibroblasts, chondrocytes, and other musculoskeletal tissues is believed to contribute to the characteristic tropism of CHIKV for joints, thereby linking viral replication with both acute arthritis and the development of chronic rheumatologic sequelae [16,17].
Disease severity is largely determined by the magnitude of the host inflammatory response rather than by direct viral cytopathic effects alone. Infection triggers the release of numerous pro-inflammatory cytokines and chemokines, promoting recruitment of monocytes, macrophages, neutrophils, and lymphocytes to infected tissues. While these responses are essential for viral clearance, excessive or prolonged immune activation has been consistently associated with severe clinical manifestations and persistent joint inflammation. Patients with severe or fatal disease frequently exhibit markedly elevated circulating concentrations of inflammatory mediators, highlighting the central role of immune dysregulation in CHIKV pathogenesis [13,18].
In addition to musculoskeletal involvement, CHIKV infection can compromise vascular homeostasis through direct infection of endothelial cells and secondary inflammatory mechanisms. Oxidative stress generated by increased production of reactive oxygen species (ROS) and superoxide anions promotes endothelial injury, while inflammatory mediators stimulate expression of adhesion molecules, including intercellular adhesion molecule-1 (ICAM-1), resulting in endothelial activation and leukocyte recruitment. Furthermore, induction of inducible nitric oxide synthase (iNOS) increases nitric oxide production, contributing to disruption of endothelial barrier integrity and vascular dysfunction [19].
Another important mechanism underlying severe disease is the upregulation of matrix metalloproteinases (MMPs), which degrade extracellular matrix components and weaken endothelial junctions. Increased vascular permeability may lead to plasma leakage, tissue edema, petechiae, and, in uncommon cases, hemorrhagic manifestations, hypotension, and circulatory shock. Impairment of endothelial barrier function may also facilitate viral dissemination to distant organs, potentially aggravating disease severity. Laboratory abnormalities observed during acute infection commonly include elevated acute-phase reactants, increased concentrations of inflammatory cytokines, mild thrombocytopenia, and transient coagulation abnormalities. The detection of infectious virions or viral RNA in blood, saliva, urine, and cerebrospinal fluid further demonstrates the systemic nature of CHIKV infection and supports the existence of multiple routes of viral shedding [13].
Epidemiology of Chikungunya Virus
Chikungunya virus (CHIKV) is an emerging mosquito-borne alphavirus with sustained transmission across tropical and subtropical regions of Africa, Asia, the Indian Ocean islands, and, more recently, the Americas. Since its initial isolation during an outbreak of acute febrile illness in Tanzania in 1952–1953, CHIKV has evolved from a geographically restricted pathogen into a global public health concern. Historical descriptions of dengue-like epidemics dating back to the eighteenth and nineteenth centuries suggest that chikungunya outbreaks probably occurred long before the virus was formally identified, although they were likely misclassified because of the clinical similarities between these arboviral infections.
Phylogenetic studies indicate that CHIKV originated in Africa, where it subsequently diversified into distinct evolutionary lineages. The principal African lineages include the East African (EA) and the West/Central/South African (WCSA) genotypes, whereas the Asian lineage became established after the virus spread throughout Southeast Asia. Following its emergence, CHIKV became endemic in several African countries, producing both sporadic infections and periodic epidemics. The first well-documented outbreak outside Africa occurred in Bangkok, Thailand, in 1958, marking the beginning of the virus's geographic expansion throughout Asia [8].
Transmission is maintained predominantly by Aedes aegypti and Aedes albopictus, although additional Aedes species and, less frequently, Culex mosquitoes have been implicated in sylvatic transmission cycles. Two epidemiological transmission patterns have been recognized. In Africa, the sylvatic cycle involves circulation of the virus among non-human primates and other vertebrate hosts through forest-associated mosquitoes, with occasional spillover into human populations. In contrast, the urban cycle is sustained through human–mosquito–human transmission, predominantly involving Aedes aegypti, and follows seasonal fluctuations closely associated with rainfall and vector abundance. Consequently, transmission generally reaches its highest levels during the first half of the year in the Southern Hemisphere and during the second half of the year in Mexico, Central America, and the Caribbean [21].
Although considerable progress has been made in understanding CHIKV ecology, predicting epidemic activity remains challenging. Historical observations suggest recurrent regional epidemics approximately every 7–20 years and larger global epidemic waves every 40–50 years. These cyclic patterns are thought to reflect complex interactions among viral evolution, environmental conditions, vector density, climatic variability, and the gradual accumulation or loss of population immunity [22].
The worldwide distribution of CHIKV has expanded dramatically over the past two decades. Autochthonous transmission has now been documented in more than 119 countries and territories across all six World Health Organization regions, while competent Aedes aegypti populations are established in numerous additional countries where local transmission has not yet been detected. Viral adaptation to Aedes albopictus, together with increasing international travel, urbanization, globalization, and climate change, has facilitated expansion into previously unaffected geographic areas. Collectively, these factors have resulted in more than 10 million reported cases worldwide, with an estimated 1.3 billion people currently living in areas at risk of CHIKV transmission [23,24].
Before the twenty-first century, most outbreaks remained geographically restricted to Africa and Asia. Since 2004, however, epidemic activity has intensified considerably. The outbreak that originated in Kenya and subsequently spread throughout islands of the Indian Ocean—including Réunion, Mauritius, Seychelles, Madagascar, and Mayotte—represented a turning point in the global epidemiology of CHIKV. Serological investigations performed shortly after the epidemic demonstrated exceptionally high attack rates, with seroprevalence approaching 75% in some affected communities, illustrating the remarkable transmissibility of the virus under favorable ecological conditions [25].
Europe has also experienced the consequences of increasing global mobility. Imported infections have been reported since 2006 among travelers returning from endemic regions, and in 2007 Italy documented the first locally acquired outbreak of chikungunya in Europe, confirming that autochthonous transmission can occur wherever competent mosquito vectors become established [26].
A major epidemiological shift occurred following the introduction of CHIKV into the Americas in late 2013. Rapid dissemination throughout the continent was facilitated by widespread Aedes populations and immunologically naïve human communities. Although the Asian lineage predominated during the initial epidemics between 2014 and 2020, more recent outbreaks in Brazil, Paraguay, Bolivia, and several Caribbean countries have identified circulation of the WCSA lineage, raising concerns regarding viral evolution, lineage replacement, and future epidemic dynamics [23].
According to the Pan American Health Organization (PAHO), nearly 1.8 million suspected chikungunya cases were reported across the Americas during the first two epidemic years (2014–2015). Although annual case numbers subsequently declined, transmission resurged in 2023, when more than 411,000 suspected cases and 515 deaths were reported. During 2024, approximately 428,000 additional cases and 213 deaths were documented, coinciding with the simultaneous resurgence of dengue throughout the region [27].
Mexico detected its first imported case in Jalisco in May 2014, followed by the first locally acquired infection in Chiapas later that year. Molecular surveillance demonstrated predominance of the Asian genotype during the initial epidemic period. National surveillance identified 2015 as the year of greatest transmission, with more than 12,500 confirmed autochthonous infections, particularly between May and August. Since 2019, reported case numbers have declined substantially, with only sporadic cases identified annually. The highest disease burden has consistently been concentrated in southern and coastal states, whereas central and northwestern regions have experienced considerably lower transmission intensity. Adults between 25 and 44 years of age have represented the most frequently affected population [28].
Although nationwide transmission has remained relatively limited in recent years, localized outbreaks continue to occur. For example, an outbreak reported in Chiapas during 2015 involved 67 laboratory-confirmed cases, predominantly among individuals between 10 and 59 years of age, and was associated with the Asian lineage transmitted by Aedes aegypti [29]. Likewise, a seroepidemiological investigation conducted among febrile patients in Guerrero identified evidence of previous CHIKV infection in 28.3% of participants, while 11% demonstrated serological findings compatible with acute infection [30].
The continuing geographic expansion of CHIKV, its capacity to produce explosive epidemics, and the considerable burden associated with chronic musculoskeletal disease have positioned chikungunya among the priority pathogens for vaccine research and development. In recognition of its epidemic potential, the Coalition for Epidemic Preparedness Innovations (CEPI) incorporated CHIKV into its priority portfolio in 2018, reinforcing international efforts to accelerate vaccine development and improve global preparedness for future outbreaks.
Clinical presentation and disease course
Clinical manifestations of chikungunya virus (CHIKV) infection evolve through three clinically recognized but overlapping stages: the acute, post-acute, and chronic phases. Although the duration and severity of symptoms vary among individuals, this classification provides a practical framework for understanding disease progression and guiding patient management [31,32,33,34].
Acute Phase
The acute phase usually extends for up to two weeks following symptom onset and is characterized by the abrupt development of high fever accompanied by intense, frequently disabling polyarthralgia. Joint pain is typically bilateral and symmetrical, predominantly involving the wrists, ankles, hands, and feet, although larger joints may also be affected. Additional manifestations commonly include myalgia, headache, fatigue, and a maculopapular rash that generally develops during the first week of illness [35].
Although systemic manifestations usually improve within several days, the intensity of the inflammatory response during the acute stage appears to influence long-term outcomes. Patients presenting with severe polyarthritis or marked inflammatory activity are more likely to experience persistent musculoskeletal symptoms after resolution of the acute infection [36]. Less common but clinically important complications have also been reported, including neurological, cardiovascular, hepatic, renal, and ocular involvement, particularly among neonates, older adults, and individuals with underlying medical conditions [37,38,39].
Post-Acute Phase
The post-acute stage generally encompasses the period from approximately two weeks to three months after the onset of illness. During this interval, many patients continue to experience recurrent or persistent joint pain, morning stiffness, tenosynovitis, or inflammatory arthritis, with symptoms often fluctuating over time. This transitional phase reflects ongoing immune-mediated inflammation despite resolution of viremia and may represent an important step in the progression toward chronic rheumatologic disease in susceptible individuals [40,41].
Chronic Phase
The chronic phase is defined by the persistence or recurrence of articular manifestations for more than three months after the initial infection. Chronic chikungunya arthritis may continue for months or even years and is believed to result from sustained immune activation rather than active viral replication alone. Persistent synovitis, inflammatory arthritis, chronic arthralgia, fatigue, and functional impairment represent the principal long-term consequences of infection and account for a substantial proportion of the overall disease burden. These chronic manifestations significantly affect quality of life, daily activities, and healthcare utilization, reinforcing the importance of effective preventive measures, including vaccination [40,41].
Immunopathogenesis and Implications for Vaccine Development
During the acute phase of chikungunya virus (CHIKV) infection, high levels of viremia are accompanied by robust activation of the innate immune response, characterized by increased expression of proinflammatory mediators such as IL-6, IL-8, IFN-α, IP-10, MCP-1, and MIG. Multiple studies have demonstrated associations between elevated levels of IL-1β, IL-17A, IL-27, and granulocyte–macrophage colony-stimulating factor (GM-CSF) and the severity of acute joint manifestations. Type I interferon signaling plays a critical role in viral control, and impaired interferon responses have been associated with more severe disease phenotypes. [42,43]
In the chronic phase, accumulating evidence suggests that persistent inflammation and immune activation may continue despite the absence of detectable infectious virus in synovial fluid. Viral RNA and antigens have been identified in synovial macrophages months after acute infection, together with infiltration by natural killer cells and CD4⁺ T lymphocytes. Although the prevalence of chronic manifestations gradually declines over time, a substantial proportion of patients continue to experience persistent joint pain long after the acute phase of infection. High viral loads and intense inflammatory responses during the acute phase have been consistently identified as predictors of chronic arthralgia. In this context, elevated levels of IL-6, GM-CSF, TNF-α, IL-1β, IL-5, and IL-12 during early infection have been proposed as immunological markers associated with progression toward chronic disease. [44,45,46].
Clinical Outcomes and Immune Protection
Although Most CHIKV infections are self-limited, severe clinical manifestations and fatalities may occur, particularly among neonates, older adults, pregnant women, and individuals with underlying medical conditions. Reported complications include neurological disorders, myocarditis, cardiac dysfunction, acute kidney injury, and, less frequently, multiorgan involvement, emphasizing that chikungunya is not exclusively a musculoskeletal disease [47].
The humoral immune response develops rapidly following infection. CHIKV-specific IgM antibodies become detectable within the first days after symptom onset and are subsequently followed by the production of neutralizing IgG antibodies, predominantly of the IgG3 subclass. These antibodies play a central role in viral clearance and are considered the principal correlate of long-term protective immunity against reinfection [48].
Current evidence indicates that natural infection generally induces durable immune memory, providing sustained protection against subsequent exposure to homologous viral strains. Nevertheless, the persistence of chronic inflammatory manifestations in a substantial proportion of patients demonstrates that protective immunity does not necessarily prevent long-term immunopathological sequelae. This apparent dissociation between viral clearance and chronic inflammation underscores the need for vaccines capable of eliciting robust neutralizing antibody responses while minimizing excessive or persistent immune activation [49].
These observations have important implications for vaccine development. An ideal CHIKV vaccine should not only generate durable protective immunity against infection but also reduce the incidence of chronic musculoskeletal complications that account for much of the long-term clinical and socioeconomic burden associated with chikungunya.
Diagnosis of Chikungunya Virus Infection
Accurate laboratory confirmation of chikungunya virus (CHIKV) infection depends primarily on the timing of specimen collection in relation to symptom onset. Current World Health Organization (WHO) recommendations recognize three complementary diagnostic approaches: molecular detection of viral RNA, serological testing, and viral isolation. Selection of the most appropriate method should be guided by the stage of infection, as viral replication predominates during the early acute phase, whereas antibody-based assays become increasingly informative after seroconversion [52].
During the first week of illness, when viremia is highest, nucleic acid amplification techniques—particularly quantitative reverse-transcription polymerase chain reaction (RT-qPCR)—represent the preferred diagnostic method because of their high sensitivity and specificity. Viral isolation may also be performed during this period by inoculating clinical specimens into susceptible cell lines such as Vero, BHK-21, or HeLa cells, where characteristic cytopathic effects generally become evident within several days. Although viral isolation remains the reference standard for confirming viable virus, its routine clinical use is limited by prolonged turnaround times and the requirement for biosafety level 3 (BSL-3) laboratory facilities [53].
As viremia declines, serological assays become the cornerstone of laboratory diagnosis. Anti-CHIKV IgM antibodies are typically detectable between 3 and 8 days after symptom onset, may persist for several months, and in some individuals remain measurable for up to two years. CHIKV-specific IgG antibodies usually appear shortly thereafter, generally between days 4 and 10, and may persist for many years, reflecting previous infection and long-term humoral immunity. Enzyme-linked immunosorbent assay (ELISA) remains the most widely used serological platform for detecting both antibody classes because of its practicality and diagnostic performance [54].
Because no single laboratory method is optimal throughout the entire course of infection, diagnostic interpretation should always consider the patient's clinical presentation and the interval between symptom onset and specimen collection. Molecular testing is recommended during the viremic phase, whereas serological assays are more appropriate once the humoral immune response has developed. This complementary diagnostic strategy maximizes diagnostic accuracy and facilitates appropriate clinical management and epidemiological surveillance.
Table 1 and Table 2 summarize the currently available laboratory methods, their recommended timing according to disease stage, and their reported diagnostic performance.

Treatment

To date, no specific antiviral therapy has been approved for the treatment of chikungunya virus (CHIKV) infection. Consequently, clinical management remains primarily supportive and is directed toward alleviating symptoms, maintaining adequate hydration, preventing complications, and preserving functional status. Because debilitating polyarthralgia and myalgia are the most prominent clinical manifestations of the disease, effective pain control constitutes the cornerstone of patient management. Supportive care may also include psychological support and patient education, particularly for individuals experiencing prolonged or disabling symptoms [56].
Acetaminophen (paracetamol) is generally recommended as the initial pharmacological option for controlling fever and mild-to-moderate pain. Nevertheless, clinicians should remain aware of its potential hepatotoxicity, especially in patients receiving high cumulative doses or those with pre-existing liver disease. When pain is insufficiently controlled, additional analgesic agents, including tramadol, codeine, or other opioid medications, may be considered according to symptom severity and individual patient characteristics.
The role of non-steroidal anti-inflammatory drugs (NSAIDs) during the acute phase of chikungunya remains controversial. Although several clinical guidelines support their use after dengue virus infection has been excluded, other recommendations advise caution because NSAIDs may increase the risk of bleeding, acute kidney injury, and other adverse events, particularly in patients with dehydration or unrecognized dengue coinfection. Therefore, exclusion of dengue should be considered before initiating NSAID therapy in regions where both arboviruses co-circulate.
Overall, treatment strategies should be individualized according to disease severity, patient age, underlying comorbidities, and the presence of complications. As current therapeutic options are limited to supportive care, the absence of effective antiviral agents further emphasizes the importance of preventive interventions, including vaccination and integrated vector-control strategies, to reduce the clinical and public health burden of chikungunya.
Chronic Phase Management
Management of chronic chikungunya disease aims to control persistent inflammation, relieve pain, preserve joint function, and improve long-term quality of life. Because chronic musculoskeletal manifestations may persist for months or even years after the acute infection, treatment should be individualized according to symptom severity, functional impairment, and the degree of inflammatory arthritis.
Therapeutic options include analgesics, short courses of corticosteroids, disease-modifying antirheumatic drugs (DMARDs), and, in selected cases, antimalarial agents such as chloroquine or hydroxychloroquine. Among DMARDs, methotrexate has demonstrated the greatest clinical benefit in patients with persistent inflammatory arthritis, improving pain, joint function, and overall quality of life. Corticosteroids may also provide symptomatic relief during inflammatory flares when carefully administered for limited periods.
Assessment of treatment response should incorporate validated clinical instruments, including the Visual Analog Scale (VAS), the Routine Assessment of Patient Index Data 3 (RAPID3), and the Disease Activity Score-28 (DAS28), which allow standardized evaluation of pain intensity, functional disability, inflammatory activity, and patient-reported outcomes.
Although no antiviral therapy modifies chronic disease progression, early recognition and appropriate management of inflammatory arthritis may reduce long-term disability. In selected patients with severe acute polyarthritis, short courses of low-dose dexamethasone have been reported to decrease symptom severity and shorten recovery time when conventional analgesic therapy is insufficient
Severe Chikungunya Disease
Although most CHIKV infections are self-limited, severe disease may develop in susceptible individuals. Reported complications include respiratory failure, myocarditis, cardiovascular instability, acute hepatitis, acute kidney injury, hemorrhagic manifestations, and neurological involvement such as encephalitis or encephalopathy. Hospital admission is recommended for patients presenting with hemodynamic instability, severe pain refractory to medical treatment, clinically significant bleeding, organ dysfunction, or decompensation of underlying comorbidities. Early multidisciplinary management is essential to reduce morbidity and mortality associated with severe infection.
Management in Vulnerable Populations

Pregnancy

Pregnant women should receive supportive care, with acetaminophen considered the preferred analgesic and antipyretic throughout pregnancy. Aspirin and non-steroidal anti-inflammatory drugs are generally avoided because of their potential fetal risks, including premature closure of the ductus arteriosus, impaired fetal renal function, and adverse pregnancy outcomes. Maternal and fetal monitoring is recommended, particularly during the third trimester. When maternal infection occurs during the highly viremic period immediately before delivery, delaying childbirth, when clinically feasible, may reduce the risk of vertical transmission. Current evidence does not support cesarean delivery as an effective strategy to prevent mother-to-child transmission, and transmission through breast milk has not been demonstrated [57].
Older Adults and Patients with Comorbidities
Older adults, particularly those over 60 years of age, and individuals with chronic medical conditions are at increased risk of severe or atypical disease and adverse clinical outcomes. Close clinical observation and early referral to hospital care are recommended whenever deterioration or decompensation of underlying diseases is suspected [57].
Pediatric Chikungunya
In children, chikungunya is generally a self-limiting illness with an excellent prognosis, although infants—particularly neonates—and children with neurological or hemodynamic complications are at greater risk of severe disease. Because no antiviral therapy is currently available, treatment remains supportive and focuses on maintaining adequate hydration, controlling fever and pain with acetaminophen, and monitoring for warning signs.
Most pediatric patients can be managed as outpatients. However, severe manifestations—including encephalitis, seizures, circulatory shock, respiratory failure, or multiorgan dysfunction—require hospitalization and, in some cases, intensive care support. Management may include hemodynamic stabilization, anticonvulsant therapy, respiratory support, and treatment of concurrent infections such as dengue or bacterial coinfections when present. Non-steroidal anti-inflammatory drugs should be introduced cautiously and only after dengue infection has been reasonably excluded [57].
Overall prognosis in children is favorable, with more than 90% achieving complete recovery and mortality remaining below 1%. Nevertheless, infants younger than one year are at increased risk of severe complications, including capillary leak syndrome, hyponatremia, shock, and multiorgan failure. Although long-term sequelae are uncommon, chronic arthralgia has been reported in approximately 9–16% of pediatric patients. Children with congenital infection or severe neurological involvement may subsequently develop developmental delay, language impairment, epilepsy, or other neurological sequelae requiring prolonged multidisciplinary follow-up [57].
Transmission, Risk Factors, and Prediction of Chikungunya Outbreaks
Transmission
The continued expansion of chikungunya virus (CHIKV) is largely driven by the remarkable ecological adaptability of its mosquito vectors. Human transmission is sustained predominantly by Aedes aegypti and Aedes albopictus, two species that have successfully colonized tropical, subtropical, and increasingly temperate environments. Their broad geographic distribution, close association with human settlements, and efficient vector competence have facilitated the worldwide emergence and re-emergence of chikungunya [58,59,60].
Transmission occurs through two principal epidemiological cycles. In endemic regions of Africa, a sylvatic cycle maintains viral circulation among non-human primates and other vertebrate hosts through forest-associated mosquitoes, with occasional spillover into humans. Outside these settings, transmission is maintained almost exclusively through the urban human–mosquito–human cycle, where Aedes aegypti serves as the principal vector responsible for epidemic spread.
Risk Factors
The epidemiology of chikungunya is influenced by a complex interaction of environmental, climatic, demographic, and socioeconomic determinants. Although temperature and rainfall strongly influence mosquito development, survival, and viral replication, studies conducted in Mexico indicate that socioeconomic conditions frequently play an even greater role in determining transmission intensity.
Limited access to healthcare, inadequate water supply, deficient sanitation, poor housing conditions, rapid urbanization, and poverty create favorable conditions for mosquito breeding and sustained viral transmission. Climatic variables nevertheless remain important, particularly in regions where seasonal increases in rainfall and temperature accelerate vector proliferation and enhance viral circulation.
Among environmental predictors, rainfall and ambient temperature consistently demonstrate the strongest association with outbreak occurrence, whereas altitude and minimum precipitation appear to contribute less substantially to predictive models. These findings highlight the multifactorial nature of chikungunya transmission and emphasize the importance of integrating environmental and social determinants into surveillance systems [67].
Prediction of Outbreaks
Accurately forecasting chikungunya outbreaks remains challenging because surveillance systems frequently underestimate disease burden owing to asymptomatic infections, limited laboratory confirmation, delayed case reporting, and surveillance fatigue [53].
Recent advances in artificial intelligence and machine-learning approaches have improved the capacity to predict arboviral transmission. In Mexico, the eXtreme Gradient Boosting (XGBoost) algorithm has demonstrated superior predictive performance compared with conventional statistical models for estimating the incidence of dengue, Zika, and chikungunya. Its ability to analyze nonlinear relationships among climatic, environmental, and epidemiological variables enables more accurate identification of areas at increased risk for future outbreaks [67].
Prevention and Control (Rewritten)
Early identification of emerging outbreaks depends on robust surveillance systems capable of integrating epidemiological, entomological, climatic, and laboratory information in real time. Prompt detection of suspected cases, together with continuous monitoring of mosquito populations and environmental conditions, allows public health authorities to implement timely interventions aimed at limiting viral transmission [69].
Although considerable progress has been achieved in vector-control strategies, sustained control of chikungunya remains difficult because of rapid vector dispersion, insecticide resistance, human mobility, and repeated viral introduction into susceptible communities. Mathematical transmission models indicate that rapid case detection combined with targeted perifocal vector-control measures can substantially reduce epidemic size when implemented early during outbreaks. These interventions are most effective when integrated with existing dengue control programs and coordinated public health responses [58].
Current evidence identifies integrated vector management as the cornerstone of chikungunya prevention. Recommended measures include elimination of mosquito breeding sites, strengthening entomological surveillance, environmental sanitation, risk-based vector monitoring, and implementation of habitat suitability models to identify areas at greatest risk of transmission. In Mexico, the discrepancy between reported arboviral cases and documented Aedes distribution in numerous municipalities highlights the need for more comprehensive surveillance systems and improved integration of epidemiological and entomological data.
Community participation is equally important for sustainable vector control. Public health campaigns should promote elimination of standing water, installation of window and door screens, appropriate use of insect repellents, protective clothing, mosquito nets, and reduction of outdoor exposure during periods of peak mosquito activity. These relatively simple interventions remain essential components of integrated prevention programs [70].
The Pan American Health Organization (PAHO) and the World Health Organization (WHO) recommend strengthening surveillance capacity, diagnostic services, clinical management, and integrated vector-control programs for chikungunya and other emerging arboviral diseases. Public health preparedness should also incorporate genomic surveillance to monitor circulating CHIKV lineages and detect viral mutations that may influence transmissibility or vector adaptation. Continuous molecular surveillance of the Asian, East/Central/South African (ECSA), and Indian Ocean Lineage (IOL) genotypes provides valuable information for anticipating future epidemic patterns and supporting evidence-based public health decision-making.
Integration of genomic analyses with epidemiological surveillance, human mobility data, and environmental monitoring offers an opportunity to improve outbreak prediction and optimize preventive interventions. Such comprehensive surveillance systems will also be essential for evaluating the future impact of vaccination programs and guiding evidence-based immunization policies in endemic regions.
Overall, effective control of chikungunya requires a multidisciplinary approach combining surveillance, vector management, environmental interventions, community engagement, and vaccination. These complementary strategies provide the greatest opportunity to reduce transmission and mitigate the long-term health and socioeconomic consequences of CHIKV infection [23].
Vaccines against chikungunya
Recent advances in vaccinology have transformed the prevention of chikungunya virus (CHIKV) infection, culminating in the licensure of the first vaccines specifically designed to prevent this emerging arboviral disease. Several vaccine platforms—including live-attenuated, virus-like particle (VLP), viral-vector, inactivated, and nucleic acid-based technologies—have been investigated. Among these, live-attenuated and VLP-based vaccines have progressed furthest in clinical development and currently represent the most advanced preventive strategies.
Live-Attenuated Vaccine: Ixchiq® (Valneva)
The live-attenuated vaccine VLA1553 (Ixchiq®, Valneva) was developed from the LR2006 OPY1 isolate belonging to the East/Central/South African (ECSA) lineage. Viral attenuation was achieved through deletion of 61 amino acids within the nsP3 protein, a modification that substantially reduces viral replication while preserving strong immunogenicity. This rationally designed attenuation strategy enables induction of protective immune responses after a single vaccine dose without compromising genetic stability.
Clinical development demonstrated excellent immunogenicity, with seroconversion rates approaching 99% following a single administration. Neutralizing antibody responses remained detectable in more than 96% of vaccinated individuals six months after immunization, and extended follow-up has confirmed persistence of protective antibody levels for at least two years. More recent immunogenicity data indicate maintenance of protective immunity for four years or longer across different age groups [71,72,80].
Overall, the vaccine has shown an acceptable safety profile. The most frequently reported adverse events have been mild to moderate and include headache, fever, myalgia, arthralgia, and transient fatigue. Safety analyses have demonstrated a reactogenicity profile comparable to that observed with other licensed live-attenuated viral vaccines [71,73].
Ixchiq® became the first licensed chikungunya vaccine following approval by the U.S. Food and Drug Administration (FDA) in November 2023 for adults at increased risk of exposure. Subsequent regulatory approvals were granted in Canada, the United Kingdom, and the European Union [74,75,78,79].
Post-licensure pharmacovigilance identified a small number of serious adverse events among older adults, prompting temporary modifications to vaccination recommendations by several regulatory agencies. These events generated substantial scientific discussion and led to the publication of multiple expert commentaries addressing the interpretation of available safety data and appropriate risk–benefit assessment for older individuals [75,76,77].
Real-world experience has expanded considerably since vaccine introduction. During the 2025 chikungunya outbreak on La Réunion Island, approximately 40,000 individuals received Ixchiq®, representing the largest post-licensure vaccination experience reported to date. These data are expected to provide valuable information regarding vaccine effectiveness, durability of protection, and long-term safety under outbreak conditions [80,81].
Virus-Like Particle Vaccine: Vimkunya® (Bavarian Nordic)
Virus-like particle (VLP) technology represents an attractive alternative vaccine platform because it reproduces the structural organization of native virions without containing replicative viral genetic material. Consequently, VLP vaccines combine excellent immunogenicity with a favorable safety profile.
The CHIKV VLP vaccine originally developed as VRC-CHKVLP059-00-VP incorporates the structural proteins of the Senegal 37997 strain, including the capsid, E3, E2, 6K, and E1 proteins. These proteins self-assemble into particles that closely resemble authentic CHIKV virions, thereby inducing potent humoral immune responses while eliminating the possibility of viral replication [82].
Clinical studies have demonstrated robust immunogenicity together with an excellent tolerability profile. Most adverse events have been mild to moderate, and vaccine-induced neutralizing antibody responses have been comparable to those achieved with other advanced CHIKV vaccine platforms [83,84].
Commercialized as Vimkunya® by Bavarian Nordic, the vaccine received FDA approval in 2025 and was subsequently authorized by the European Medicines Agency (EMA) for use in individuals 12 years of age and older. Like Ixchiq®, Vimkunya® is administered as a single-dose vaccine, facilitating its implementation in travelers and potentially in future vaccination campaigns should broader indications become available [85,86].
Future Perspectives
Although two chikungunya vaccines are now licensed, important challenges remain before widespread implementation in endemic countries can be considered. Current recommendations are primarily directed toward travelers or individuals at increased risk of exposure rather than routine vaccination of populations living in endemic areas.
Vaccine platform Virus-like particle (VLP) Live-attenuated
Manufacturer Bavarian Nordic Valneva SE
Dose schedule Single dose Single dose
Age indication ≥12 years ≥18 years*
Route of administration Intramuscular Intramuscular
Replication Non-replicating Replication-competent, attenuated
Immune response Neutralizing antibodies Neutralizing antibodies
Regulatory approvals FDA (2025), EMA FDA (2023), EMA, Health Canada, MHRA
Main advantages Excellent safety profile; suitable for immunocompromised individuals** Strong immunogenicity after a single dose
Main considerations Limited post-marketing experience Live vaccine; post-marketing safety monitoring continues
For countries such as Mexico, several critical questions remain unresolved, including identification of priority populations, cost-effectiveness, duration of protection, booster requirements, and the optimal integration of vaccination into existing arboviral control programs. Individuals at increased risk of severe disease or chronic musculoskeletal sequelae—including older adults and patients with underlying comorbidities—may ultimately represent important target populations for future vaccination strategies.
An important milestone toward broader implementation is currently underway in Brazil, where Valneva and Instituto Butantan have initiated a large pilot immunization program involving approximately 500,000 adults between 18 and 59 years of age. This initiative, implemented outside the context of an active outbreak, is expected to generate valuable evidence regarding vaccine performance, feasibility, and public health impact under routine conditions [87].
Finally, numerous additional vaccine candidates—including mRNA, viral-vector, inactivated, and next-generation live-attenuated platforms—remain under clinical investigation. Continued advances in vaccine development, together with post-marketing surveillance and real-world effectiveness studies, will play a crucial role in defining the future role of immunization as a central component of integrated chikungunya prevention strategies.

Conclusions

Chikungunya virus (CHIKV) has evolved from a geographically restricted arbovirus into a persistent global public health challenge. Its continued geographic expansion, driven by climate change, rapid urbanization, increasing human mobility, and the widespread distribution of Aedes vectors, underscores the likelihood of recurrent outbreaks in endemic and non-endemic regions alike. Although Mexico experienced its largest epidemics during 2014–2015, the persistence of competent vectors and favorable ecological conditions indicates that future outbreaks remain a realistic threat.
Beyond the acute febrile illness, chikungunya imposes a substantial long-term burden because of the high frequency of chronic inflammatory musculoskeletal complications. Persistent arthralgia and chronic arthritis significantly impair quality of life, reduce functional capacity, and generate considerable socioeconomic costs. These long-term consequences reinforce the need to shift public health efforts from an exclusively reactive approach toward comprehensive prevention strategies.
The Immunization Committee of the Mexican Association of Pediatric Infectious Diseases (AMIP) considers that reliance on vector control alone is insufficient to sustainably reduce the burden of chikungunya in Mexico. While integrated vector management, entomological surveillance, environmental interventions, and rapid outbreak detection remain essential components of disease control, the availability of safe and effective vaccines represents a major opportunity to strengthen national prevention strategies.
The recent approval of Ixchiq® and Vimkunya® marks a new era in chikungunya prevention. Although important questions remain regarding long-term effectiveness, post-marketing safety, duration of protection, optimal target populations, and implementation strategies in endemic countries, current evidence supports the incorporation of vaccination into comprehensive public health planning whenever supported by local epidemiological conditions and regulatory recommendations.
Based on the available scientific evidence, the Immunization Committee of AMIP recommends that Mexico strengthen its national chikungunya preparedness strategy through an integrated approach that includes:
  • Enhanced epidemiological, entomological, climatic, and genomic surveillance.
  • Early laboratory confirmation and timely outbreak detection.
  • Continuous evaluation of disease burden and chronic sequelae.
  • Assessment of cost-effectiveness and implementation strategies for chikungunya vaccines in endemic settings.
  • Identification and prioritization of populations at greatest risk of severe disease or long-term disability.
  • Promotion of collaborative research to generate national evidence capable of informing future immunization policies.
The Committee further considers that future vaccination policies should be developed through multidisciplinary collaboration involving public health authorities, academic institutions, scientific societies, and regulatory agencies. Such recommendations should remain evidence-based and be continuously updated as additional data on vaccine effectiveness, safety, duration of protection, and real-world implementation become available.
In conclusion, the Immunization Committee of the Mexican Association of Pediatric Infectious Diseases considers that chikungunya should no longer be viewed solely as an emerging arboviral infection but as a long-term public health priority for Mexico and the Americas. Integrating vaccination with surveillance, vector control, community engagement, and clinical preparedness offers the greatest opportunity to reduce transmission, prevent chronic disability, and mitigate the future health and economic impact of chikungunya.

Limitations

This position paper has several limitations. Evidence was derived from published literature and official reports, which may be subject to publication bias, heterogeneity in study design, and evolving epidemiological data. Formal systematic review methodology and risk-of-bias assessments were not performed because the primary aim of this manuscript was to provide expert guidance and public health recommendations relevant to Mexico.

Funding

Valneva only funded the article publication fees, however, had no role in the study design, data collection, data analysis, data interpretation, or manuscript preparation.

Conflicts of Interest

The authors declare no conflicts of interest related to this work.

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Table 1. Diagnostic tests for CHIK infection. 
Table 1. Diagnostic tests for CHIK infection. 
According to the of days of the illness
Acute 0-5 (7 days) RT - PCR /qRT –PCR for CHIKV
Acute 1-7 days Antigen test
Convalescent >5-7 days ELISA IgM
(MAC-ELISA)
Late/past >2-3 weeks IgG(4x increase per title)
Andrew, A., Navien, T., Yeoh, T., Citartan, M., Mangantig, E., Sum, M., Ch’ng, E., & Tang, T. Diagnostic accuracy of serological tests for the diagnosis of Chikungunya virus infection [55]
Table 2. Diagnostic performance of currently available laboratory assays for the detection of chikungunya virus (CHIKV) infection. 
Table 2. Diagnostic performance of currently available laboratory assays for the detection of chikungunya virus (CHIKV) infection. 
Diagnostic assay Sensitivity (%) Specificity (%) PPV (%) NPV (%)
RT-PCR 88.5 100 100 97.5
Standard Diagnostics CHIKV IgM ELISA 3.9 92.5 10 81.6
Novatec CHIKV IgM Capture ELISA 3.9 92.5 10 81.6
Novatec CHIKV IgM Capture ELISA 76.9 91.9 100 97.5
Novatec CHIKV IgG ELISA 80 100 100 95.6
Viral isolation 15–50 100 100 63
Abbreviations: PPV, positive predictive value; NPV, negative predictive value; RT-PCR, reverse transcription polymerase chain reaction; IgM, immunoglobulin M; IgG, immunoglobulin G; ELISA, enzyme-linked immunosorbent assay. Data adapted from Refs. [50,51].
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